800-872-2273

Clinical Trials and Studies

Your participation matters. Help us discover and cure!

Contact us at (800) USC-CARE (800-872-2273)

Study Title Principal Investigator
Genomics of Young Lung Cancer Study
PRIMARY OBJECTIVES: I. To perform comprehensive genomic analysis of young lung cancer patients' samples to facilitate delivery of targeted therapies and clinical trial enrollment. II. To characterize the impact of young age at lung cancer diagnosis on the genomic landscape of primary lung cancer. III. To establish a prospective registry of young lung cancer patients for both tumor and germline next generation sequencing. OUTLINE: Tissue and blood samples are analyzed via next generation sequencing and whole exome sequencing. After completion of study, patients are followed up every 3 months for up to 3 years.
Not recruiting | Lung Cancer | Multisite
Barbara Gitlitz
Assessing the Patient Experience in Cancer Care: An Observational Communication Study
Not recruiting | Brain Cancer | Multisite
Jon Tilburt
An Open-Label, Multicenter, Global Phase 2 Basket Study of Entrectinib for the Treatment of Patients With Locally Advanced or Metastatic Solid Tumors That Harbor NTRK1/2/3, ROS1, or ALK Gene Rearrangements
Open | Brain Cancer | Multisite
Clinical Trials
A Randomized Phase III Trial for Surgically Resected Early Stage Non-small Cell Lung Cancer: Crizotinib Versus Observation for Patients With Tumors Harboring the Anaplastic Lymphoma Kinase (ALK) Fusion Protein
PRIMARY OBJECTIVES: I. To evaluate whether adjuvant therapy with crizotinib will result in improved overall survival (OS) for patients with stage IB >= 4 cm, II and IIIA, ALK-positive non-small cell lung cancer (NSCLC) following surgical resection. SECONDARY OBJECTIVES: I. To evaluate and compare disease-free survival (DFS) associated with crizotinib. II. To evaluate the safety profile of crizotinib when given in the adjuvant therapy setting. III. To collect tumor tissue and blood specimens for future research. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive crizotinib orally (PO) twice daily (BID) on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. ARM B: Patients undergo observation. After completion of study treatment, patients are followed up every 6 months if < 4 or 5 years from study entry, and every 12 months if 5-10 or 6-10 years from study entry.
Open | Lung Cancer | Multisite
David Gerber
Feasibility Study of Stereotactic Body Radiation Therapy Followed by Wedge Resection for Peripherally Located Early Stage Non-small Cell Lung Cancer
PRIMARY OBJECTIVES: I. To assess the safety and feasibility of a wedge resection following stereotactic body radiation therapy (SBRT) for early stage peripheral non-small cell lung cancer (NSCLC). SECONDARY OBJECTIVES: I. To assess pathologic response rates to SBRT as determined by pathologic examination of resected tumors. II. To prospectively assess patient quality of life when treated with SBRT and wedge resection. TERTIARY OBJECTIVES: I. To describe the location of viable tumor and to correlate pathologic response rates with radiation dose, size of tumor, and tumor histology. II. To correlate pathologic response rates and functional imaging with pre- and post-treatment dual-input perfusion (DP)-computed tomography (CT) and positron emission tomography (PET)-CT. III. To correlate changes in serum levels of deoxyribonucleic acid (DNA) methylation and circulating tumor cells (CTC) with pathologic response rates. OUTLINE: Patients undergo stereotactic radiosurgery every other day for 3 or 5 fractions (depending on the size tumor and proximity to the chest wall). Within 4-6 weeks after completion of stereotactic radiosurgery, patients undergo wedge resection. After completion of study treatment, patients are followed up at 1, 3, 6, and 12 months.
Not recruiting | Lung Cancer | Not Multisite
Eugene Chung
A Biomarker-Driven Master Protocol for Previously Treated Squamous Cell Lung Cancer (Lung-Map)
PRIMARY OBJECTIVES: Screening component: I. To establish a National Clinical Trials Network (NCTN) mechanism for genomically screening large but homogeneous cancer populations and subsequently assigning and accruing simultaneously to a multi-sub-study ?Master Protocol.? II. To evaluate the screen success rate defined as the percentage of screened patients that register for a therapeutic sub-study. Sub-study-specific Objectives: Design #1: Phase II/III Design: III. To evaluate if there is sufficient evidence to continue to the Phase III component of the sub-study by comparing investigator-assessed progression-free survival (IA-PFS) between investigational therapy versus standard therapy (SoC) in patients with advanced stage refractory squamous cell carcinoma (SCCA) of the lung. (Phase II) IV. To determine if there is both a statistically and clinically-meaningful difference in IA-PFS among advanced stage refractory SCCA of the lung randomized to receive investigational therapy versus SoC. (Phase III) V. To compare overall survival (OS) in patients with advanced stage refractory SCCA of the lung randomized to investigational therapy versus SoC. (Phase III) Design #2: Phase II followed by Phase III (Sequential Phase II to Phase III): VI. To evaluate the objective response rate (confirmed and unconfirmed, complete and partial). (Phase II) VII. To determine if there is both a statistically and clinically-meaningful difference in IA-PFS among advanced stage refractory SCCA of the lung randomized to receive investigational therapy versus SoC. (Phase III) VIII. To compare overall survival (OS) in patients with advanced stage refractory SCCA of the lung randomized to investigational therapy versus SoC. (Phase III) SECONDARY OBJECTIVES: Sub-study-specific Objectives: Design #1: Phase II/III Design: I. To compare response rates (confirmed and unconfirmed, complete and partial responses) among patients randomized to receive investigational therapy versus SoC. (Phase II) II. To evaluate the frequency and severity of toxicities associated with investigational therapy versus SoC. (Phase II) III. To evaluate the duration of response (DoR) among patients who achieve a complete response (CR) or a partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) (1.1). (Phase II) III. To compare the response rates (confirmed and unconfirmed, complete and partial) among patients randomized to receive investigational therapy versus SoC. (Phase III) IV. To evaluate the frequency and severity of toxicities associated with investigational therapy versus SoC. (Phase III) Design #2: Phase II followed by Phase III (Sequential Phase II to Phase III): V. To evaluate PFS and OS with investigational therapy. (Phase II) VI. To evaluate the DoR among patients who achieve a CR or PR (confirmed and unconfirmed) by RECIST 1.1. (Phase II) VII. To evaluate the frequency and severity of toxicities associated with investigational therapy. (Phase II) VIII. To compare the response rates (confirmed and unconfirmed, complete and partial) among patients randomized to receive investigational therapy versus SoC. (Phase III) IX. To evaluate the frequency and severity of toxicities associated with investigational therapy versus SoC. (Phase III) TERTIARY OBJECTIVES: I. To evaluate the treatment arm randomization acceptance rate (TARAR) within each treatment arm of each sub-study defined as the percentage of patients randomized to a treatment arm that receive any protocol treatment. (Design #1: Phase II/III Design) II. To identify additional predictive tumor/blood biomarkers that may modify response or define resistance to the targeted therapy (TT)/targeted therapy combination (TTC) beyond the chosen biomarker for biomarker-driven sub-studies. III. To evaluate potentially predictive biomarkers for non-match therapy (NMT) in the non-match studies. IV. To identify potential resistance biomarkers at disease progression. V. To establish a tissue/ blood repository from patients with refractory SCCA of the lung. OUTLINE: Patients are assigned to a biomarker-driven targeted therapy phase II study. If the objectives response rate observed is judged sufficient, patients proceed to a randomized phase III trial and are randomized to biomarker-driven targeted therapy or standard of care. S1400A: (CLOSED TO ACCRUAL 12/18/2015) Patients with tumors that do not match one of the currently active drug-biomarker combinations or did not meet the eligibility requirements for that bio-marker driven sub-study are assigned to Arm I. Upon evidence of progression following discontinuation of 12 months of treatment, patients may restart treatment for up to 12 months with the same treatment guidelines followed during the initial 12-month treatment period (Arm III). ARM I: (CLOSED TO ACCRUAL 12/18/2015) Patients receive anti-B7H1 monoclonal antibody MEDI4736 intravenously (IV) over 60 minutes on day 1. Treatment repeats every 14 days for 12 months in the absence of disease progression or unacceptable toxicity. ARM II (CLOSED TO ACCRUAL 4/2015): Patients receive docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. (closed to accrual with Revision #2 4/22/15) ARM III: For patients assigned to Arm 1, MEDI4736: Upon evidence of progression following discontinuation of 12 months of treatment, patients may restart treatment with Arm 3, MEDI4736 for up to 12 months with the same treatment guidelines followed during the initial 12-month treatment period. Patients will only be able to restart treatment once; thus a maximum of two 12-month periods will be allowed. Patients receive anti-B7H1 monoclonal antibody MEDI4736 intravenously (IV) over 60 minutes on day 1. Treatment repeats every 14 days for 12 months in the absence of disease progression or unacceptable toxicity. S1400B (CLOSED TO ACCRUAL 12/12/2016): Patients with tumors positive for phosphoinositide 3-kinase (PI3KCA) are assigned to Arm I. Patients currently on Arm 2, docetaxel will be given the option to re-register to Arm 3, GCD-0032 after disease progression on current treatment (Arm III). ARM I: Patients receive taselisib orally (PO) daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM II (CLOSED TO ACCRUAL 12/18/2015): Patients receive docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. (closed to accrual with Revision #3 12/18/2015) ARM III: Re-Registration Treatment with GDC-0032 (Taselisib) Upon progression patients in Arm 2 may be eligible for Re-Registration to receive GDC-0032. Patients receive taselisib orally (PO) daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. S1400C (CLOSED TO ACCRUAL 09/01/2016): Patients with tumors positive for cyclin dependent kinase 4 (CDK4), cyclin D1 (CCND1), cyclin D2 (CCND2), and cyclin D3 (CCND3) are assigned to Arm I. Patients currently on Arm 2, docetaxel will be given the option to re-register to Arm 3, palbociclib, after disease progression on current treatment (Arm III). ARM I: Patients receive palbociclib PO on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM II (CLOSED TO ACCRUAL 12/18/2015): Patients receive docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. (closed to accrual with Revision #3 12/18/2015) ARM III: Re-Registration Treatment with Palbociclib. Upon progression patients in Arm 2 may be eligible for Re-Registration to receive palbociclib. Patients receive palbociclib PO on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. S1400D (CLOSED TO ACCRUAL 10/31/2016): Patients with tumors positive for fibroblast growth factor receptor (FGFR) 1, FGFR2, and FGFR3 are assigned to Arm I. Patients currently on Arm 2, docetaxel will be given the option to re-register to Arm 3, AZD4547, after disease progression on current treatment (Arm III). ARM I: Patients receive FGFR inhibitor AZD4547 PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM II (CLOSED TO ACCRUAL 12/18/2015): Patients receive docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. (closed to accrual with Revision #3 12/18/2015) ARM III: Re-Registration Treatment with AZD4547. Upon progression patients in Arm 2 may be eligible for Re-Registration to receive AZD4547. Patients receive FGFR inhibitor AZD4547 PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. S1400E (CLOSED TO ACCRUAL 11/25/2014): Patients with tumors positive for met proto-oncogene (MET) are randomized to 1 of 2 treatment arms. (permanently closed to accrual on 11/25/14) ARM I: Patients receive rilotumumab IV on day 1 and erlotinib hydrochloride PO daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive erlotinib hydrochloride PO daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. S1400F: Patients with disease progression during or after prior anti-PD-1 or anti-PD-L1 antibody monotherapy as their most recent line of treatment receive durvalumab (IV over 60 minutes) and tremelimumab (IV over 60 minutes) on day 1 for courses 1-4 and durvalumab IV alone on day 1 of course 5 and subsequent courses until disease progression or unacceptable toxicity. Courses repeat every 28 days. S1400G: Patients with tumors positive for homologous recombination repair deficiency receive talazoparib PO daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. S1400I: Patients with tumors that do not match one of the currently active drug-biomarker combinations or did not meet the eligibility requirements for that bio-marker driven sub-study are randomized to 1 of 2 treatment arms. ARM I: Patients receive nivolumab IV over 30 minutes on day 1 and ipilimumab IV over 60 minutes on day 1 of every third course. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive nivolumab IV over 30 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, all patients are followed up periodically for up to 3 years from date of screening registration.
Not recruiting | Lung Cancer | Multisite
Vassiliki Papadimitrakopoulou
A Phase II Trial of AZD9291 (Osimertinib) With or Without Bevacizumab in Patients With EGFR Mutation Positive NSCLC and Brain Metastases
PRIMARY OBJECTIVES: I. To determine the progression-free survival with AZD9291 (osimertinib) plus bevacizumab compared to AZD9291 (osimertinib) alone. SECONDARY OBJECTIVES: I. To assess the safety and tolerability of the combination of AZD9291 (osimertinib) and bevacizumab. II. To evaluate the time to progression in the central nervous system (CNS) with AZD9291 (osimertinib) plus bevacizumab versus single-agent osimertinib. III. To determine the overall response rate and the intracranial response rate to the combination versus single agent. IV. To assess the overall survival in patients receiving AZD9291 (osimertinib) plus bevacizumab compared to AZD9291 (osimertinib) alone. TRANSLATIONAL OBJECTIVES: I. To investigate mechanisms of sensitivity and resistance to combination AZD9291 (osimertinib) plus bevacizumab versus AZD9291 (osimertinib) by molecularly characterizing tumor samples including T790M status. II. To assess whether circulating tumor deoxyribonucleic acid (DNA) in plasma can be used as an indicator of sensitivity and resistance to treatment. III. To determine whether an angiogenic signature using a multiplex panel array is associated with benefit from the combination of AZD9291 (osimertinib) plus bevacizumab. IV. To investigate angiogenesis, immune and signaling pathway markers in tumor samples to determine biomarkers predictive of benefit from combination therapy. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive osimertinib orally (PO) once daily (QD) on days 1-21 and bevacizumab intravenously (IV) over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive osimertinib PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for a minimum of 4 weeks.
Open | Lung Cancer | Multisite
Sarah Goldberg
2N-13-2: A Randomized, Phase 3 Study of Ganetespib in Combination with Docetaxel versus Docetaxel Alone in Patients with Advanced Non-Small-Cell Lung Adenocarcinoma
This is an open-label, multicenter, randomized Phase 3 study of patients with Stage IIIB/IV NSCLC of adenocarcinoma histology.Primary Objective is to evaluate and compare overall survival (OS) in non-small cell lung cancer (NSCLC) patients with adenocarcinoma histology treated with ganetespib in combination with docetaxel versus docetaxel alone.Ganetespib is a novel synthetic small molecule that binds to the adenosine triphosphate (ATP) pocket in the N-terminus of Hsp90 and demonstrates significant activity for down-regulating Hsp90 client protein levels. This ability to impact a broad array of important oncogenes and cell signaling kinases is reflected in ganetespibs activity across a wide variety of tumor cell types.Patients will be randomized in a 1:1 ratio to receive either ganetespib in combination with docetaxel or docetaxel alone. The study will enroll approximately 500 patients, 12 from USC, over a planned 12-month period, and patients will be randomized into one of two treatment arms.
Recruiting | Lung Cancer | Multisite
Barbara Gitlitz
Randomized Phase II/III Trial of Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance for Small Cell Lung Cancer
PRIMARY OBJECTIVES: I. Determine whether the 12-month intracranial relapse rate following hippocampal avoidance (HA)-prophylactic cranial irradiation (PCI) is non-inferior compared to the rate following PCI for patients with small cell lung cancer (SCLC). (Randomized Phase II Component [Non-Inferiority]) II. Determine whether HA-PCI reduces the likelihood of 6-month deterioration from baseline in Hopkins Verbal Learning Test (HVLT)-Revised (R) delayed recall compared to PCI for patients with SCLC. (Phase III Component [Efficacy]) SECONDARY OBJECTIVES: I. Compare time to cognitive failure, as measured by a battery of tests (HVLT-R, Controlled Oral Word Association [COWA] test, and Trail Making Test [TMT] parts A and B), after PCI versus HA-PCI in SCLC. II. Compare time to cognitive failure as separately measured by each test (HVLT-R for Total Recall and Delayed Recognition, COWA test, and TMT parts A and B), after PCI versus HA-PCI for SCLC. III. Compare patient-reported cognitive functioning and other quality of life domains (assessed by the European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire [QLQ]-Core [C]30 and BN20) between PCI versus HA-PCI for patients with SCLC. IV. Compare overall survival after PCI versus HA-PCI for patients with SCLC. V. Compare 12-month intracranial relapse rate (at completion of phase III) and time to intracranial relapse after PCI versus HA-PCI for patients with SCLC. VI. Evaluate adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) criteria. VII. Correlate changes in health-related quality of life (HRQOL) domains with changes in cognitive testing outcomes following PCI versus HA-PCI for patients with SCLC. VIII. Assess cost-effectiveness of HA-PCI (intensity modulated radiation therapy [IMRT]) and PCI (3-dimensional conformal radiation therapy [3DCRT]) using the EuroQual (EQ)-5-Dimensions (5D)-5L. TERTIARY OBJECTIVES: I. Collect serum, whole blood, and urine for future translational research analyses. II. Evaluate baseline magnetic resonance (MR) imaging biomarkers of white matter injury and hippocampal volumetry as potential predictors of cognitive decline and differential benefit from HAPCI as compared to PCI. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients undergo PCI using 3DCRT daily for 2 weeks. ARM II: Patients undergo PCI with HA using IMRT daily for 2 weeks. After completion of study treatment, patients are followed every 3 months for 1 year, then every 6 months until 3 years and then annually until death.
Open | Lung Cancer | Multisite
Vinai Gondi
Dynamic Perfusion Computed Tomography Changes After Stereotactic Body Radiation Therapy for Localized Non-small Cell Lung Cancer
PRIMARY OBJECTIVES: I. To describe perfusion computed tomography (CT) parameters and their changes in non-small cell lung cancer (NSCLC) tumors prior to, during, 1 month after, and 3 months after stereotactic body radiation therapy (SBRT). SECONDARY OBJECTIVES: I. To correlate tumor perfusion parameters with clinical tumor response on follow up per standard of care. TERTIARY OBJECTIVES: I. To correlate changes in serum levels of deoxyribonucleic acid (DNA) methylation and circulating tumor cell (CTC) with clinical response rates and perfusion parameters. OUTLINE: Patients undergo dynamic perfusion computed tomography (DPCT) at baseline, during SBRT (after 2 of 3 fractions or 3 of 5 fractions), and then at 1 and 3 months post stereotactic body radiation therapy. After completion of study, patients are followed up at 6, 12, 18, and 24 months.
Open | Lung Cancer | Not Multisite
Christopher Lee
Collaborative Advanced Stage Tissue Lung Cancer (CASTLE) Network
Because of the historically poor outcomes of lung cancer patients, suboptimal therapeutic efficacy, and significant side effects of chemotherapy, and the need to choose more efficacious treatment regimens, and patients most likely to benefit from them, there is a need to predict a priori whether an individual patient's tumor will respond to a particular therapeutic agent. However, virtually all lung cancer tumor samples available today are from resection specimens so direct, intra-patient molecular-clinical therapy correlations are impossible. Without the critical mass of tissue and data necessary to identify optimal molecular targets for lung cancer and drugs active against these targets, new discoveries that offer the only hope of long-term survival for many lung cancer patients remain elusive. This study facilitates the collection of biospecimens from advanced lung cancer patients and routine determination of a panel of documented clinically significant biomarkers. In addition, it will centrally integrate and standardize research tissue samples with corresponding proteomic, genomic, molecular and clinical data across a multitude of institutions and oncology networks
Open | Lung Cancer | Multisite
LUX-Lung 8: A Randomized, Open-label Phase III Trial of Afatinib Versus Erlotinib in Patients With Advanced Squamous Cell Carcinoma of the Lung as Second-line Therapy Following First-line Platinum-based Chemotherapy
Completed | Lung Cancer | Multisite
Boehringer Ingelheim
The Use of Social Media Listening for Targeted Recruitment of Twitter Users in LA County in Cancer Trials Compared to Historic Recruitment Data: A Mixed-Methods Study
PRIMARY OBJECTIVES: I. Examine the feasibility (acceptance among University of Southern California [USC] Norris study team members and Twitter users in Los Angeles [LA] county) of targeted social media listening (SML) via Twitter as a tool for enhancing recruitment to cancer trials. II. Gain preliminary data on the impact (i.e., numbers recruited versus projected accrual compared to historic recruitment) of targeted social media listening (SML) as a tool for enhancing recruitment to cancer trials among Twitter users in LA county. III. Estimate the effect size of the number of people enrolled associated with the use of targeted social media listening (SML) via Twitter as a tool for enhancing recruitment to cancer trials. OUTLINE: Patients who mention specific cancer disease keywords and/or hashtags are identified and receive a message via Twitter. Patients are then contacted for recruitment into a clinical trial.
Open | Breast Cancer | Not Multisite
Thomas Buchanan
View Research Profile
Longitudinal Monitoring of Tumor Specific Mutations in Patients With Lung Cancer
PRIMARY OBJECTIVES: I. To evaluate the ability of next generation sequencing (NGS) to monitor the evolution of cancer-specific mutations in patients undergoing treatment for non-small cell lung carcinoma and for whom the molecular profile of the tumor cells prior to treatment is known. II. Compare the sensitivity of digital droplet polymerase chain reaction (ddPCR) to that of NGS for detecting the appearance of EGFR T790M mutations in patients treated with an EGFR tyrosine kinase inhibitor. OUTLINE: Patients undergo collection of blood samples at baseline and every 12 weeks for up to 6 times.
Open | Lung Cancer | Not Multisite
Pamela Ward
A Phase 1b/2 Study of OMP-59R5 in Combination With Etoposide and Platinum Therapy in Subjects With Untreated Extensive Stage Small Cell Lung Cancer (PINNACLE)
Recruiting | Lung Cancer | Multisite
Barbara Gitlitz
Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST)
PRIMARY OBJECTIVES: I. To centrally test resected non-small cell lung cancer (NSCLC) for genetic mutations to facilitate accrual to randomized adjuvant studies. II. To obtain clinically annotated tumor tissue and patient-matched non-malignant deoxyribonucleic acid (DNA) from peripheral blood, as well as detailed epidemiologic and clinical follow-up data, to allow clinically annotated advanced genomic analyses in concert with the National Cancer Institute (NCI) Center for Cancer Genomics (CCG). SECONDARY OBJECTIVES: I. To characterize the natural history of molecularly characterized NSCLC to allow subsequent development of targeted therapies against genotype-defined subpopulations in the adjuvant and recurrent settings. II. To cross-validate local genotyping assays for epidermal growth factor receptor (EGFR) and anaplastic lymphoma receptor tyrosine kinase (ALK) with a central reference standard. EXPLORATORY OBJECTIVES: I. To study the genomic evolution of lung cancers by comparing genomic characteristics at resection and at recurrence. II. To understand reasons behind lack of enrollment to adjuvant targeted therapy studies for potentially eligible patients. III. To study the clinical significance of circulating tumor DNA within the plasma cell-free DNA (cfDNA) from early stage lung cancer patients. OUTLINE: STEP 1 (SCREENING): Patients undergo collection of blood and tissue samples for EGFR, ALK, and programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1)/cytotoxic t-lymphocyte-associated protein 4 (CTLA-4) testing via direct sequencing, fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Patients that have had surgery prior to pre-registration will submit samples from the previous surgery for testing. STEP 2 (TREATMENT): Patients with a mutation targeted by one or more of the investigational drugs used in this study or those without mutations are assigned to 1 of 3 treatment subprotocols. A081105: Patients are randomized to 1 of 4 treatment arms. ARM A (BLINDED ERLOTINIB- CLOSED 06/14/17): Blinded patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. ARM B (PLACEBO- CLOSED 06/14/17): Patients receive placebo PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. ARM C (UNBLINDED ERLOTINIB): Unblinded patients receive erlotinib hydrochloride PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. ARM D (OBSERVATION): Patients (including patients previously randomized to placebo) undergo observation at least every 6 months for 2 years. E4512: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive crizotinib PO twice daily (BID) on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. ARM B: Patients undergo observation. EA5142: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. ARM II: Patients are followed serially with imaging for 1 year. After completion of study, patients that are not enrolled on either A081105, E4512, or EA5142 are followed up every 6 months for 5 years.
Open | Lung Cancer | Multisite
Geoffrey Oxnard
A Phase III, Double-Blinded, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Neoadjuvant Treatment With Atezolizumab or Placebo in Combination With Platinum-Based Chemotherapy in Patients With Resectable Stage II, IIIA, or Select IIIB Non−Small Cell Lung Cancer
Open | Lung Cancer | Multisite
Clinical Trials
Randomized Phase II Study of AZD6244 MEK-Inhibitor With Erlotinib in KRAS Wild Type and KRAS Mutant Advanced Non-Small Cell Lung Cancer
Background: Lung Cancer is the leading cause of death among both men and women. Of the approximately 172,000 patients that are diagnosed every year with non small cell lung cancer (NSCLC) in the US, 55% present with advanced stage disease. The current treatment for advanced NSCLC is first line chemotherapy with a platinum-based doublet. Second line treatment for recurrent or progressive disease includes treatment with chemotherapy or treatment with an oral EGFR (epidermal growth factor receptor) tyrosine kinase inhibitor. Several mechanisms of resistance to EGFR tyrosine kinase inhibitors have been discovered. Presence of KRAS mutations is one of them. AZD6244 (ARRY-142886) is an investigational drug that is orally available and targets the critical kinase (MEK) in the mitogen-activated protein (MAP) kinase signal transduction pathway which is activated in NSCLC and is downstream of EGFR. Objectives: - Determine the progression free survival (PFS) using the combination of AZD6244 and erlotinib in patients with wild type KRAS advanced NSCLC - Determine the clinical response rate (PR (partial response) + CR (complete response)) either monotherapy AZD6244 or the combination AZD6244 plus erlotinib in patients with mutated KRAS advanced NSCLC - Evaluate disease control rate (PR+CR+SD (stable disease)) and overall survival in both patient groups. - Determine a safety profile for use of AZD6244 in combination with erlotinib in patients with advanced NSCLC. - Measure serological markers to evaluate if these markers are correlated with tumor response. - Measure changes in a tumors MIB-1 (Ki-67) rate and pERK levels in response to treatment with AZD6244. Eligibility: - Patients with pathologically confirmed NSCLC not amenable to potentially curative therapy and having progressed after being treated with at least one prior platinum containing chemotherapy regimen, or having refused cytotoxic chemotherapy. - Progressive disease should be documented prior to enrollment on the study. - Patient should not have more than 2 prior chemotherapy regimens. - Measurable disease by RECIST (Response Evaluation Criteria in Solid Tumors) criteria. - Adequate renal, cardiac, hepatic and hematopoietic functions - No major surgery, radiotherapy, or chemotherapy within 28 days of enrollment. Design: - Patients will be stratified on the basis on their KRAS mutational status. Wild-Type KRAS patients will be randomized to receive either single agent erlotinib 150 mg/day or the combination of erlotinib 100 mg/day plus AZD6244 at 150 mg/day. KRAS mutant patients will be randomized to receive AZD6244 monotherapy at a dose of 75 mg twice per day, or the combination AZD6244 at 150 mg/day plus erlotinib 100 mg/day. - Treatment will continue until disease progression. - Toxicity will be assessed every cycle by the CTCAE (Common Terminology Criteria for Adverse Events) Version 4.0. - Tumor assessments by RECIST 1.1 criteria will be performed every 2 cycles (one cycle is 28 days). - Correlative studies including initial tumor mutational analysis and tissue immunohistochemistry (IHC) studies will be done on existing tumor blocks, or re-biopsied tissue prior to enrollment. - Patients will be evaluated for the potential to undergo repeat tumor biopsy after 1 cycle of therapy. Tumors will be assessed for MIB-1 (Ki-67) and pERK levels by IHC. - The study will accrue up to 40 patients with wild-type KRAS NSCLC and up to 60 patients with mutated KRAS NSCLC.
Not recruiting | Lung Cancer | Multisite
Arun Rajan
A Phase 1/2, Open-Label, Safety, Pharmacokinetic and Preliminary Efficacy Study of Oral Rociletinib in Patients With Previously Treated Mutant EGFR Non-Small Cell Lung Cancer (NSCLC)
Lung cancer remains the most common cancer worldwide with non-small cell lung cancer accounting for 85% of cases. Cytotoxic chemotherapy has been the mainstay of patients with NSCLC; however, survival rates remain low and toxicity is significant. Molecularly targeted therapies have proven to be superior to chemotherapy for NSCLC patients whose tumors have mutations in EGFR. Recent studies have established tyrosine kinase inhibitors (TKIs) as the gold standard for treating EGFR-mutation-positive NCSLC. However, patients on TKIs eventually progress, and in approximately 50% of cases, progression is due to development of an additional mutation called T790M. There are currently no approved therapies for patients who progress on TKIs. Rociletinib may provide an effective therapy for a patient population with few alternative treatment options. Nonclinical data demonstrate that rociletinib inhibits T790M. It is anticipated that rociletinib may promote cell death in tumor cells with the T790M mutation, thus providing possible therapeutic benefit in patients who have developed T790M-mediated resistance to first generation TKIs. This is a two-part, open-label study of oral rociletinib administered daily in previously treated NSCLC patients who have documented evidence of an activating mutation in the EGFR gene and have failed treatment with an EGFR inhibitor such as erlotinib, gefitinib or afatinib. This study will include 2 parts: Phase 1 (completed enrolment): Dose-escalation Period with 21-day cycles; optional Treatment Extension Period starting on Day 22 Phase 2 (currently enrolling): Evaluation of activity and safety in patients with the T790M EGFR mutation who have: Cohort A - Progressed on EGFR directed therapy (irrespective of the number and order of previous lines of NSCLC therapy) or Cohort B - Progression on the first single agent EGFR directed therapy received and also had no more than one previous line of chemotherapy
Not recruiting | Lung Cancer | Multisite
Barbara Gitlitz
A Phase 2 Study of ARQ 197 in Patients With Previously-Treated Malignant Mesothelioma
PRIMARY OBJECTIVES: I. To determine the objective response rate of patients with malignant mesothelioma who are treated with ARQ 197 (tivantinib). SECONDARY OBJECTIVES: I. To determine the progression-free survival of patients with malignant mesothelioma who are treated with ARQ 197. II. To determine the toxicity experienced by patients with malignant mesothelioma who are treated with ARQ 197. III. To determine median and overall survival of patients with malignant mesothelioma who are treated with ARQ 197. TERTIARY OBJECTIVES: I. To determine the frequency of mesenchymal-epithelial transition (MET) gene amplification in malignant mesothelioma patient tumor samples, and to correlate the results with MET immunohistochemistry (IHC). II. To determine whether MET gene amplification results in increased sensitivity to ARQ 197 as observed by improved clinical outcomes (response rate [RR] and progression free survival [PFS]) compared to those without MET gene over-expression/amplification. III. To determine whether high baseline serum hepatocyte growth factor (HGF), as well as changes in serum HGF during treatment at pre-defined early time points, correlate with treatment efficacy and clinical outcome, as measured by response rate and progression-free survival. IV. To identify mutations by sequencing of specific areas of the MET gene in tumor samples (semaphorin [SEMA], jumonji [JM] and tyrosine kinase domains). V. To perform immunohistochemistry (IHC) of mesothelioma tumors for HGF, MET and phosphorylated (p)-MET (pY1003 and pY1230/34/35). VI. To assess serum HGF and serum soluble MET levels by enzyme linked immunosorbent assay (ELISA) (R&D systems) pre-treatment, after 2 cycles and at disease progression. OUTLINE: Patients receive tivantinib orally (PO) twice daily (BID). Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 1 year.
Terminated | Lung Cancer | Multisite
Hedy Kindler
A Dose Finding Study Followed by Phase II Randomized, Placebo-Controlled Study of Veliparib (ABT-888) Added to Chemoradiotherapy With Carboplatin and Paclitaxel for Unresectable Stage III Non-small Cell Lung Cancer (NSCLC), (NCI Study Number 8811)
PRIMARY OBJECTIVES: I. To establish the maximum tolerated dose (MTD) and the recommended phase II dose of ABT-888 (veliparib) when given concurrently with standard carboplatin/paclitaxel and radiotherapy in patients with unresectable stage III non-small cell lung cancer (NSCLC). (Phase I) II. To assess whether carboplatin/paclitaxel plus ABT-888 compared with carboplatin/paclitaxel plus placebo improves progression-free survival (PFS) in patients with unresectable stage III NSCLC. (Phase II) III. To compare overall survival (OS) in patients treated with carboplatin/paclitaxel and radiotherapy plus ABT-888 to those treated with carboplatin, paclitaxel and radiotherapy plus placebo. (Phase II) IV. To assess the response rate (confirmed and unconfirmed, complete and partial responses) and disease control rate in the subset of patients with measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. (Phase II) V. To assess the safety and toxicity profile of the regimen. (Phase II) SECONDARY OBJECTIVES: I. To collect tumor tissue from pretreatment biopsies (archival samples) for biomarker studies, including poly (ADP-ribose) polymerase 1 (PARP) activity by measuring the levels of poly-ADP-ribose, gamma-H2A histone family, member X (gamma-H2AX), and messenger ribonucleic acid (mRNA) expression levels of deoxyribonucleic acid (DNA) repair enzymes such as excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1)/x-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1). II. To collect blood samples for evaluation of gamma-H2AX (circulating tumor cells) and other relevant future studies. OUTLINE: This is a phase I, dose-escalation study of veliparib followed by a randomized phase II study. PHASE I: INDUCTION THERAPY: Patients undergo 3-dimensional conformal radiation therapy (3D-CRT) once daily (QD), 5 days a week, for 6 weeks. Patients also receive veliparib orally (PO) twice daily (BID) on days 1-43 and carboplatin intravenously (IV) over 30 minutes and paclitaxel IV over 1 hour on days 1, 8, 15, 22, 36, and 43 in the absence of disease progression or unacceptable toxicity. Patients without disease progression after completion of chemoradiotherapy undergo consolidation therapy. CONSOLIDATION THERAPY: Beginning within 4-6 weeks of chemotherapy and radiation therapy, patients receive veliparib PO BID on days 1-7 (course 1) and 22-28 (course 2) and carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1 and on day 22 of course 2. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. PHASE II: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients undergo 3D-CRT and receive veliparib, carboplatin, and paclitaxel as in Phase I induction and consolidation therapy. ARM II: Patients undergo 3D-CRT as in arm I. Patients also receive placebo PO BID on days 1-43 and carboplatin and paclitaxel as in Phase I. Within 4-6 weeks after completion of chemotherapy and radiation therapy, patients receive placebo on days 1-7 and carboplatin and paclitaxel as in Phase I. After completion of study treatment, patients are followed up every 4 months for first 2 years and then every 6 months until 5 years.
Active, not recruiting | Lung Cancer | Multisite
Athanassios Argiris
A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GS-5745 as Monotherapy and in Combination With Chemotherapy in Subjects With Advanced Solid Tumors
Not recruiting | Lung Cancer | Multisite
Gilead Director
Phase II Trial of XL184 (Cabozantinib) Plus Erlotinib in Patients With Advanced EGFR-Mutant Non-small Cell Lung Cancer (NSCLC) Who Have Progressed on Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) Therapy
PRIMARY OBJECTIVES: I. To evaluate for efficacy by response rate (RR) when patients with advanced non-small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) mutation who have progressed following EGFR tyrosine kinase inhibitor (TKI) therapy are treated with XL184 (cabozantinib [cabozantinib-s-malate]) and erlotinib (erlotinib hydrochloride). SECONDARY OBJECTIVES: I. Determine progression free survival (PFS) for combination XL184 (cabozantinib) and erlotinib in EGFR mutation positive patients following progression on erlotinib. II. Assess overall survival. III. Evaluate change in tumor growth rate on XL184 (cabozantinib) and erlotinib. IV. Evaluate type, severity, duration and outcome of toxicities. V. Correlate outcome with tumor biomarkers such as met proto-oncogene (MET) amplification, T790M mutation, and serum markers of the vascular endothelial growth factor (VEGF) and MET pathways in a preliminary manner. OUTLINE: Patients receive cabozantinib-s-malate orally (PO) daily and erlotinib hydrochloride PO once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 12 weeks for 1 year and then annually thereafter.
Not recruiting | Lung Cancer | Multisite
Karen Reckamp
A Randomized, Phase IIB/III Study of Ganetespib (STA-9090) in Combination With Docetaxel Versus Docetaxel Alone in Subjects With Stage IIIb or IV Non-Small-Cell Lung Cancer
Preliminary signals of clinical activity of ganetespib as a single agent have been observed in NSCLC. A novel approach to treatment of NSCLC is the combination of Hsp90 inhibitors, such as ganetespib, and taxanes. Such combinations have shown potential for synergy in preclinical and clinical evaluations with other Hsp90 inhibitors. Preclinical studies with ganetespib and taxanes have indicated that the combination of these drugs was more effective than either drug alone at inducing cell death, and an ongoing phase 1 study indicates that the combination is well tolerated and warrants systematic evaluation in a larger study.
Not recruiting | Lung Cancer | Multisite
Barbara Gitlitz
A Randomized Phase II Trial of Cytotoxic Chemotherapy With or Without Epigenetic Priming in Patients With Advanced Non-small Cell Lung Cancer
PRIMARY OBJECTIVES: I. Percentage of patients progression-free at 6 months from time of randomization. SECONDARY OBJECTIVES: I. Progression-free survival (PFS). II. Overall Survival (OS). OUTLINE: Patients are randomized to 1 of 3 treatment arms. ARM A: Patients receive azacitidine subcutaneously (SC) on days 1-6 and 8-10 and entinostat orally (PO) on days 3 and 10. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or progressive disease receive chemotherapy of the treating oncologist's choice comprising irinotecan hydrochloride intravenously (IV) on day 1, docetaxel IV on day 1, pemetrexed disodium IV on day 1, or gemcitabine hydrochloride IV on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive azacitidine PO on days 1-21 and entinostat PO on days 3 and 10. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or progressive disease receive chemotherapy of the treating oncologist's choice as in Arm A. ARM C: Patients receive chemotherapy of the treating oncologist's choice as in Arm A. After completion of treatment, patients are followed up every 3-6 months for 24 months and then yearly thereafter.
Not recruiting | Lung Cancer | Multisite
Julie Brahmer
An Open-label, Randomized Phase 3 Efficacy Study of ASP8273 vs Erlotinib or Gefitinib in First-line Treatment of Patients With Stage IIIB/IV Non-small Cell Lung Cancer Tumors With EGFR Activating Mutations
Not recruiting | Lung Cancer | Multisite
Medical Monitor
A Phase 2 Study of MEDI4736 (Durvalumab) and Tremelimumab Alone or in Combination With High or Low-Dose Radiation in Metastatic Colorectal and NSCLC
PRIMARY OBJECTIVES: I. To assess safety and tolerability of combined checkpoint blockade with MEDI4736 (durvalumab) and tremelimumab alone or with high or low-dose radiation in non-small cell lung cancer (NSCLC). (NSCLC Cohort) II. To compare the overall response (excluding the irradiated lesion[s]) between combined checkpoint blockade with MEDI4736 and tremelimumab alone or combined checkpoint blockade with low or high dose radiation. (NSCLC Cohort) III. To assess safety and tolerability of combined checkpoint blockade with MEDI4736 and tremelimumab with high or low-dose radiation. (Colorectal Cohort) IV. To determine the overall response rate (excluding the irradiated lesion[s]) with combined checkpoint blockade with MEDI4736 and tremelimumab with either low or high dose radiation. (Colorectal Cohort) SECONDARY OBJECTIVES: I. To estimate median progression-free survival and overall survival. (NSCLC Cohort) II. To determine local control within the irradiated field(s) and abscopal response rates. (NSCLC Cohort) III. To evaluate associations between PD-L1 expression as well as levels of infiltrating CD3+, CD8+ T-cells and overall response. (NSCLC Cohort) IV. To explore changes in PD-L1 expression, circulating T-cell populations, T-cell infiltration, ribonucleic acid (RNA) expression, spatial relationship of immune markers, and mutational burden as a result of low or high dose radiation. (NSCLC Cohort) V. To estimate median progression-free survival and overall survival. (Colorectal Cohort) VI. To determine local control within the irradiated field and abscopal response rates. (Colorectal Cohort) VII. To evaluate associations between PD-L1 expression as well as levels of infiltrating CD3+ CD8+ T-cells and overall response. (Colorectal Cohort) VIII. To evaluate changes between PD-L1 expression as well as levels of infiltrating CD3+, CD8+ T-cells induced by targeted low or high dose radiation. (Colorectal Cohort) IX. To explore changes in circulating T-cell populations, T-cell infiltration, RNA expression, spatial relationship of immune markers, and mutational burden as a result of low or high dose radiation. (Colorectal Cohort) OUTLINE: Patients with NSCLC are randomized to Arm A, B, or C. Patients with colorectal cancer are randomized to Arm B or C. COHORT 1: Patients with NSCLC are randomized to 1 of 3 arms. ARM A: Patients receive tremelimumab intravenously (IV) and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses. ARM B: Patients receive tremelimumab and durvalumab and as in Arm A. Beginning at week 2, patients receive high dose radiation therapy once per day (QD) over 10 days for up to 3 fractions. ARM C: Patients receive tremelimumab and durvalumab and as in Arm A. Beginning at week 2, patients receive low dose radiation therapy every 6 hours twice per day (BID) on weeks 2, 6, 10 and 14. After completion of study treatment, patients are followed for up to 12 weeks.
Open | Lung Cancer | Multisite
Jonathan Schoenfeld
Phase I Study of TRC102 in Combination With Cisplatin and Pemetrexed in Patients With Advanced Solid Tumors / Phase II Study of TRC102 With Pemetrexed in Patients Refractory to Pemetrexed and Cisplatin or Carboplatin
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) for the combination of methoxyamine (TRC102) with pemetrexed (pemetrexed disodium) and cisplatin in patients with advanced solid tumors. (Arm A) II. To describe the toxicities of TRC102 combined with pemetrexed and cisplatin at each dose studied. (Arm A) III. To describe responses to the drug combination at each dose level. (Arm A) IV. To detect activity of the combination of TRC102 and pemetrexed, as evidenced by tumor response in patients with advanced malignant mesothelioma previously treated with pemetrexed and cisplatin. (Arm B) SECONDARY OBJECTIVES: I. To describe pharmacokinetic parameters of TRC102 given concurrent with pemetrexed and cisplatin. II. To evaluate the pharmacodynamic parameters of TRC102 given concurrently with pemetrexed and cisplatin. III. To explore the feasibility of establishing pleural and peritoneal effluent-derived cell lines and to evaluate the response of cultured pleural and peritoneal mesothelioma cells to cisplatin, pemetrexed, and TRC102. IV. To document all objective clinical responses to TRC102 in combination with pemetrexed and cisplatin. OUTLINE: This is a phase I, dose-escalation study of methoxyamine, followed by a phase II study. Patients are assigned to 1 of 2 treatment arms. ARM A: Patients receive methoxyamine orally (PO) once daily (QD) on days 1-4, pemetrexed disodium intravenously (IV) over 10 minutes, and cisplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue methoxyamine and pemetrexed disodium beyond cycle 6 if the patient continues to benefit from treatment at the discretion of the treating physician. ARM B: Patients receive methoxyamine PO QD on days 1-4 and pemetrexed disodium IV over 10 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue methoxyamine and pemetrexed disodium beyond cycle 6 if the patient continues to benefit from treatment at the discretion of the treating physician. After completion of study treatment, patients are followed up for 8 weeks.
Open | Lung Cancer | Multisite
Marianna Koczywas
A Phase II Study of Olaparib Plus Cediranib in Combination With Standard Therapy for Small Cell Lung Cancer
PRIMARY OBJECTIVES: I. To determine whether the addition of cediranib maleate (cediranib) plus olaparib as maintenance therapy, in patients with small cell lung cancer (SCLC) who have stable disease or better (non-progressive disease or non-PD) after initial therapy, leads to improved median progression-free survival (PFS), PFS is measured in months from the time of randomization to maintenance therapy (after completion of initial therapy), compared to standard therapy (no maintenance treatment. SECONDARY OBJECTIVES: I. To evaluate the impact of cediranib plus olaparib maintenance therapy on median overall survival (OS) in patients with SCLC who have non-PD after initial therapy. II. To determine whether the addition of cediranib to cisplatin/carboplatin plus etoposide during initial therapy adds benefit to response rate, median PFS and median OS. III. To assess safety and tolerability of the combination of cediranib plus olaparib during maintenance therapy. IV. To evaluate potential biomarkers of clinical benefit to olaparib/cediranib combination, including tumor proteomic and genomic markers, and circulating levels of cytokines and angiogenic factors, that that may be associated with clinical benefit. OUTLINE: INITIAL THERAPY PHASE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive carboplatin intravenously (IV) over 60 minutes or cisplatin IV over 60 minutes on day 1 and etoposide IV over 60 minutes on days 1, 2, and 3. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive treatment as in Arm I and also receive cediranib maleate orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients in Arm I who have stable disease, partial, or a complete response are randomized to receive maintenance therapy or no maintenance therapy. Patients in Arm II are assigned to receive maintenance therapy. MAINTENANCE THERAPY: Patients receive cediranib maleate PO QD and olaparib PO twice daily (BID) on days 1-28. NO MAINTENANCE THERAPY: Patients are eligible to crossover to receive treatment with cediranib maleate and olaparib upon disease progression at the treating investigator's discretion. After completion of study treatment, patients are followed up every 3-4 months for at least 1 year.
Suspended | Lung Cancer | Multisite
Leena Gandhi
A Study of HSP90 Inhibitor AT13387 Alone and in Combination With Crizotinib in the Treatment of Non-small Cell Lung Cancer (NSCLC)
This is a 3-part phase 1-2 study in patients with anaplastic lymphoma kinase (ALK) + or other potentially crizotinib-sensitive NSCLC who have been receiving crizotinib. Part A is a single-arm, Phase 1, open-label, dose escalation design in patients with NSCLC who have already been receiving crizotinib for at least 8 weeks and continue to tolerate therapy. Part B is a Phase 2, open-label, randomized continuation design comparing crizotinib alone versus the combination of crizotinib + AT13387 at the maximum tolerated dose established in Part A. Part C is an open-label, randomized, Phase 2, Simon's 2 stage design evaluating single agent AT13387 or combination AT13387 + crizotinib at the MTD established in Part A in patients who progressed on crizotinib at any time.
Not recruiting | Lung Cancer | Multisite
Jean-Charles Soria
A Randomized Phase II Study of Epigenetic Therapy With Azacitidine and Entinostat With Concurrent Nivolumab Versus Nivolumab Alone in Subjects With Recurrent Metastatic Non-Small Cell Lung Cancer.
Objective response rate to Nivolumab preceded by epigenetic priming. Response will be assessed by RECIST 1.1 criteria, baseline scans for this assessment will be the baseline scans done within 4 weeks of enrollment.
Open | Lung Cancer | Multisite
Barbara Gitlitz
An Open Label, Multicenter, Single-Arm, Expanded Access Study of Alectinib for Patients With ALK-Rearranged Non-Small Cell Lung Cancer After Disease Progression on or Intolerance to Prior ALK Tyrosine Kinase Inhibitor Therapy
Not recruiting | Lung Cancer | Multisite
Clinical Trials
A Phase II Study of the BRAF Inhibitor Dabrafenib as a Single Agent and in Combination With the MEK Inhibitor Trametinib in Subjects With BRAF V600E Mutation Positive Metastatic (Stage IV) Non-small Cell Lung Cancer
Not recruiting | Lung Cancer | Multisite
Novartis Pharmaceuticals
A Phase III Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 in Combination With Tremelimumab Therapy Versus Standard of Care Platinum-Based Chemotherapy in First-Line Treatment of Patients With Advanced or Metastatic Non Small-Cell Lung Cancer (NSCLC)
Patients will be randomized in a 1:1 to receive treatment with durvalumab + tremelimumab combination therapy or SoC therapy. The primary objective of this study is to assess the efficacy of combination treatment compared with SoC in terms of Overall Survival (OS) in patients.
Active, not recruiting | Lung Cancer | Multisite
Tony Mok
Early Diagnosis of Pulmonary Nodules Using A Plasma Proteomic Classifier, Protocol Number 1001-12
Patients must present with previously non-diagnosed lung nodules as found on CT. There is no change to the typical standard of care that any of the investigating physicians and/or centers provide the patients enrolled in this study. The data from this study will not be used to diagnose cancer nor be used to influence treatment decisions for the study participants.
Completed | Lung Cancer | Multisite
Russell Hudnall
A Phase 2, Fast Real Time Assessment of Combination Therapies in Immuno-Oncology Study in Subjects With Advanced Non-Small Cell Lung Cancer (FRACTION-Lung)
Not recruiting | Lung Cancer | Multisite
Bristol-Myers Squibb
A Phase 1-2, Open-Label, Dose-Finding, Proof of Concept, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CX-2009 in Adults With Metastatic or Locally Advanced Unresectable Solid Tumors (PROCLAIM-CX-2009)
Open | Lung Cancer | Multisite
Matthias Will
A Phase II, Multi-center, Open-label, Five-arm Study to Evaluate the Efficacy and Safety of Oral Ceritinib Treatment for Patients With ALK-positive Non-small Cell Lung Cancer (NSCLC) Metastatic to the Brain and/or to Leptomeninges
Approximately 160 patients diagnosed with ALK-positive metastatic NSCLC (according to the 7th edition of the AJCC [American Joint Committee on Cancer] Cancer Staging Manual) and active lesions in the brain and/or diagnosed with leptomeningeal carcinomatosis will be included in the study, approximately 40 patients in Arm 1 and Arm 2, approximately 30 patients in Arms 3 and Arm 4, and approximately 20 patients in Arm 5. Additional patients may be enrolled in Arm 4 to achieve approximately 60 patients in Arms 3 and 4 together (i.e. ALKi naïve patients), if enrollment rate in Arm 3 is slow. - Arm 1 will include patients with metastases in the brain without evidence of leptomeningeal carcinomatosis, previously treated with radiation to the brain and with prior exposure to an ALKi. - Arm 2 will include patients with metastases in the brain without evidence of leptomeningeal carcinomatosis, previously untreated with radiation to the brain but with prior exposure to an ALKi. - Arm 3 will include patients with metastases in the brain without evidence of leptomeningeal carcinomatosis, previously treated with radiation to the brain but with no prior exposure to an ALKi. - Arm 4 will include patients with metastases in the brain without evidence of leptomeningeal carcinomatosis, previously untreated with radiation to the brain and with no prior exposure to an ALKi - Arm 5 will include any patients with leptomeningeal carcinomatosis with or without evidence of active lesion at the baseline Gadoliniumenhanced brain MRI. Note: Previous treatment with ALK inhibitors other than crizotinib is not allowed in Arms 1, 2, and 5. Ceritinib will be administered orally once daily at a dose of 750 mg (five 150 mg capsules) on a continuous dosing schedule. The treatment period will start on Cycle 1 Day 1. Complete tumor assessments including gadolinium enhanced brain MRI will be repeated at Week 8 (on Cycle 3 Day 1) and every 8 weeks (i.e. every 2 cycles) thereafter or earlier if clinically indicated. Safety evaluations will include (S)AEs, physical examination, vital signs, ECGs, laboratory parameters and WHO performance status. Blood and CSF samples for PK will also be collected.
Not recruiting | Lung Cancer | Multisite
Novartis Pharmaceuticals
A Randomized, Double-blind, Placebo-controlled, Phase 2 Clinical Trial of Alisertib (MLN8237) in Combination With Paclitaxel Versus Placebo in Combination With Paclitaxel as Second Line Therapy for Small Cell Lung Cancer (SCLC).
The drug tested in this study is called alisertib. Alisertib is being tested to treat people who have Small Cell Lung Cancer (SCLC). This study determined the safety and efficacy for alisertib when given twice a day along with paclitaxel. This open label study enrolled 178 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the two treatment groups—which remained undisclosed to the patient and study doctor during the study (unless there is an urgent medical need) and participants were stratified at baseline as to whether brain mets were present or not; whether they were sensitive to prior therapy or were relapsed/refractory to prior therapy; and by world region: - Alisertib 40 mg + Paclitaxel 60 mg/m^2 - Paclitaxel 80 mg/m^2 + Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient All participants received treatment until their disease progressed or they experienced unacceptable alisertib-related toxicity. This multi-center trial was conducted world-wide. The overall time to participate in this study was approximately up to 22 months. Participants made multiple visits to the clinic, and were contacted by telephone every month for 6 months after the end of treatment (EOT) for follow-up assessment of progression free survival and for overall survival every 2 months until death, study closure, or 14 months after randomization of the last participant.
Not recruiting | Lung Cancer | Multisite
Medical Science
A Phase 2, Multicenter Study of Autologous Tumor Infiltrating Lymphocytes (LN 144 or LN-145) in Patients With Solid Tumors
LN-144 (Lifileucel)/LN-145 is an adoptive cell transfer therapy that utilizes an autologous TIL manufacturing process for the treatment of patients with advanced unresectable or metastatic melanoma, advanced squamous cell carcinoma of the head and neck, and non-small cell lung cancer. The adoptive cell transfer therapy used in this study involves patients receiving a nonmyeloablative (NMA) lymphocyte depleting preparative regimen, followed by infusion of autologous TIL followed by the administration of a regimen of IL-2. Patients in Cohort 1 and 2 will receive TIL plus pembrolizumab, and patients in Cohort 3 will receive TIL as a single therapy.
Open | Lung Cancer | Multisite
Iovance Monitor
A Multi-Center Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Combination With Durvalumab (MEDI4736), in Subjects With Relapsed or Refractory Solid Tumors
Not recruiting | Breast Cancer | Multisite
Isaiah Dimery
A Phase 2 Study of TH-4000 (Tarloxotinib) in Patients With EGFR-Mutant, T790M-Negative, Advanced Non-Small Cell Lung Cancer Progressing on an EGFR Tyrosine Kinase Inhibitor
A single arm open label multi-center Phase 2 study in which the pharmacokinetics, safety, tolerability and efficacy of TH-4000 (Tarloxotinib) will be assessed in patients with EGFR mutant, T790M negative advanced NSCLC. Patients must have demonstrated progression during EGFR TKI therapy. Hypoxia PET scans will be obtained in select centers to analyze potential predictors of tumor response.
Not recruiting | Lung Cancer | Multisite
Stephen Liu
A MULTICENTER, OPEN-LABEL, PHASE 1B/2 STUDY TO EVALUATE SAFETY AND EFFICACY OF AVELUMAB (MSB0010718C) IN COMBINATION WITH CHEMOTHERAPY WITH OR WITHOUT OTHER ANTI-CANCER IMMUNOTHERAPIES AS FIRST-LINE TREATMENT IN PATIENTS WITH ADVANCED MALIGNANCIES
This is a Phase 1b/2, open label, multicenter, safety, clinical activity, pharmacokinetic (PK), and pharmacodynamics (PD) study of avelumab in combination with chemotherapy with or without other anti-cancer immunotherapies, as first-line treatment of adult patients with locally advanced or metastatic solid tumors. Initially, avelumab will be evaluated in combination with pemetrexed and carboplatin in patients with advanced non-squamous non-small cell lung cancer (NSCLC) (Cohort A1) and with gemcitabine and cisplatin in patients with cisplatin-eligible urothelial cancer (UC) (Cohort A2). Given the growing preclinical and clinical indications that combinations of anti-cancer immunotherapies potentially improve patient outcomes compared to results seen with single agents, in portions of the study to be added in the future, avelumab will be evaluated in combination with both standard-of-care chemotherapy and other anti-cancer immunotherapies in patients with advanced malignancies. Each cohort in the study will consist of a Phase 1b lead-in portion to evaluate safety and a Phase 2 cohort expansion to evaluate safety and efficacy. In the Phase 1b safety lead-in portion, up to 12 patients will be enrolled into each cohort and evaluated for dose-limiting toxicities (DLT) during the first 2 cycles of treatment. If investigational products administration in a cohort is deemed safe in the Phase 1b lead-in, enrollment may be expanded into the Phase 2 cohort expansion. Up to approximately 40 patients in each cohort (including those enrolled in the Phase 1b lead-in and those enrolled in the Phase 2 cohort expansion) will be enrolled and treated with avelumab plus chemotherapy in the initial portion of the study and, in future portions of the study, with avelumab plus chemotherapy with or without other anti-cancer immunotherapies. In the Phase 1b lead-in portions of NSCLC Cohort A1 and UC Cohort A2, avelumab is dosed at 800 mg fixed dose every 3 weeks. Under Protocol Amendment 4, avelumab is dosed at 1200 mg fixed dose every 3 weeks in the Phase 1b lead-in portions of NSCLC Cohort A3 and in UC Cohort A4, in combination with the same standard-of-care chemotherapy doublets used in Cohort A1 and Cohort A2, respectively. For each tumor type, the study treatment combination with the highest avelumab dose determined to be safe may be advanced into Phase 2 cohort expansion.
Open | Lung Cancer | Multisite
Pfizer Center
SHERLOC: A Phase 2 Study of MM-121 in Combination With Docetaxel Versus Docetaxel Alone in Patients With Heregulin Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer
This study is a randomized, open-label, international, multi-center, phase 2 study in patients with Heregulin-positive NSCLC histologically classified as adenocarcinoma that have progressed following no more than two systemic therapies for locally advanced or metastatic disease, one of which must have been a platinum containing regimen. All patients will initially be screened for heregulin status. Eligible patients will be randomized to receive MM-121 in combination with docetaxel versus docetaxel alone.
Not recruiting | Lung Cancer | Multisite
MM-121 Director
Randomized Study of Erlotinib vs Observation in Patients With Completely Resected Epidermal Growth Factor Receptor (EGFR) Mutant Non-Small Cell Lung Cancer (NSCLC)
PRIMARY OBJECTIVES: I. To assess whether adjuvant therapy with erlotinib (erlotinib hydrochloride) will result in improved overall survival (OS) over observation for patients with completely resected stage IB (>= 4 cm)-IIIA epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) (confirmed centrally) following complete resection and standard post-operative therapy. SECONDARY OBJECTIVES: I. To assess whether adjuvant therapy with erlotinib will result in improved disease free survival (DFS) over observation for patients with completely resected stage IB (>= 4 cm)-IIIA EGFR mutant NSCLC (confirmed centrally) following complete resection and standard post-operative therapy, both overall and within the stage subgroups: IB and II/IIIA. II. To evaluate the safety profile of erlotinib in the adjuvant setting. III. To assess whether adjuvant therapy with erlotinib will result in improved DFS rate at 2 years, and OS rate at 5 and 10 years over observation for patients with completely resected stage IB (>= 4 cm)-IIIA EGFR mutant NSCLC (confirmed centrally) following complete resection and standard post-operative therapy, both overall and within the stage subgroups: IB and II/IIIA. IV. To assess the primary and secondary objectives in all randomized patients, regardless of central confirmation of the EGFR mutant status. V. To study detection of circulating EGFR mutations in cell-free plasma deoxyribonucleic acid (DNA) as a prognostic marker in resected early stage NSCLC. OUTLINE: Patients are randomized to 1 of 4 treatment arms. ARM A (BLINDED ERLOTINIB- CLOSED 06/14/17): Blinded patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. ARM B (PLACEBO- CLOSED 06/14/17): Patients receive placebo PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. ARM C (UNBLINDED ERLOTINIB): Unblinded patients receive erlotinib hydrochloride PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. ARM D (OBSERVATION): Patients (including patients previously randomized to placebo) undergo observation at least every 6 months for 2 years. After completion of study treatment, patients are followed up every 6 months for 4 years and then yearly for 6 years.
Open | Lung Cancer | Multisite
Ramaswamy Govindan
Pivotal, Open-label, Randomized Study of Radiosurgery With or Without Tumor Treating Fields (TTFields) (150kHz) for 1-10 Brain Metastases From Non-small Cell Lung Cancer (NSCLC)
PAST PRE-CLINICAL AND CLINICAL EXPERIENCE: The effect of the electric fields (TTFields, TTF) has demonstrated significant activity in in vitro and in vivo NSCLC pre-clinical models both as a single modality treatment and in combination with chemotherapies. TTFields have also shown to inhibit metastatic spread of malignant melanoma in in vivo experiment. In a pilot study, 42 patients with advanced NSCLC who had had tumor progression after at least one line of prior chemotherapy, received pemetrexed together with TTFields (150 kHz) applied to the chest and upper abdomen until disease progression (Pless M., et al., Lung Cancer 2011). Efficacy endpoints were remarkably high compared to historical data for pemetrexed alone. In addition, a phase III trial of Optune® (200 kHz) as monotherapy compared to active chemotherapy in recurrent glioblastoma patients showed TTFields to be equivalent to active chemotherapy in extending survival, associated with minimal toxicity, good quality of life, and activity within the brain (14% response rate) (Stupp R., et al., EJC 2012). Finally, a phase III trial of Optune® combined with maintenance temozolomide compared to maintenance temozolomide alone has shown that combined therapy led to a significant improvement in both progression free survival and overall survival in patients with newly diagnosed glioblastoma without the addition of high grade toxicity and without decline in quality of life (Stupp R., et al., JAMA 2015). Applying TTFields at 150 kHz to the brain for the treatment of 1-5 brain metastasis from NSCLC using the NovoTTF-100M device has been demonstrated to be safe in a pilot study, where patients were randomize after local therapy of their brain metastasis by neurosurgery and/or stereotactic radiosurgery to receive either NovoTTF-100M treatment or supportive care alone. Eighteen (18) patients have been enrolled in the study. There have been no device-related serious adverse events (SAE) reported to date (Brozova H., et al., Neuro Oncol 2016). DESCRIPTION OF THE TRIAL: All patients included in this trial are patients with 1-10 brain metastases from NSCLC which are amenable to stereotactic radiosurgery (SRS). In addition, all patients must meet all eligibility criteria. Eligible patients will be randomly assigned to one of two groups: 1. Patients undergo SRS followed by TTFields using the NovoTTF-100M System 2. Patients undergo SRS alone and receive supportive care. Patients in both arms of the study may receive systemic therapy for their NSCLC at the discretion of their treating physician. Patients will be randomized at a 1:1 ratio. Baseline tests will be performed in patients enrolled in both arms. If assigned to the NovoTTF-100M group, the patients will be treated continuously with the device until second intracranial progression. On both arms, patients who recur anywhere in the brain will be offered one of the following salvage treatments (according to local practice) including, but not limited to: - Surgery - Repeat SRS - Whole brain radiotherapy (WBRT) Patients on the control arm will be offered to cross over to the NovoTTF-100M arm of the study and receive TTFields after salvage therapy for second intracranial progression if the investigator believes it is in the best interest of the patient and patient agrees. SCIENTIFIC BACKGROUND: Electric fields exert forces on electric charges similar to the way a magnet exerts forces on metallic particles within a magnetic field. These forces cause movement and rotation of electrically charged biological building blocks, much like the alignment of metallic particles seen along the lines of force radiating outwards from a magnet. Electric fields can also cause muscles to twitch and if strong enough may heat tissues. TTFields are alternating electric fields of low intensity. This means that they change their direction repetitively many times a second. Since they change direction very rapidly (150 thousand times a second), they do not cause muscles to twitch, nor do they have any effects on other electrically activated tissues in the body (brain, nerves and heart). Since the intensities of TTFields in the body are very low, they do not cause heating. The breakthrough finding made by Novocure was that finely tuned alternating fields of very low intensity, now termed TTFields (Tumor Treating Fields), cause a significant slowing in the growth of cancer cells. Due to the unique geometric shape of cancer cells when they are multiplying, TTFields cause electrically-charged cellular components of these cells to change their location within the dividing cell, disrupting their normal function and ultimately leading to cell death.. In addition, cancer cells also contain miniature building blocks which act as tiny motors in moving essential parts of the cells from place to place. TTFields interfere with the normal orientation of these tiny motors related to other cellular components since they are electrically-charged as well. As a result of these two effects, tumor cell division is slowed, results in cellular death or reverses after continuous exposure to TTFields. Other cells in the body (normal healthy tissues) are affected much less than cancer cells since they multiply at a much slower rate if at all. In addition TTFields can be directed to a certain part of the body, leaving sensitive areas out of their reach. Finally, the frequency of TTFields applied to each type of cancer is specific and may not damage normally dividing cells in healthy tissues. In conclusion, TTFields hold the promise of serving as a brand new treatment for brain metastases from NSCLC with very few side effects.
Open | Brain Cancer | Multisite
Minesh Mehta
Seamless Phase I/II Study of Stereotactic Lung Radiotherapy (SBRT) for Early Stage, Centrally Located, Non-Small Cell Lung Cancer (NSCLC) in Medically Inoperable Patients
OBJECTIVES: Primary - To determine the maximum tolerated dose (MTD) of stereotactic body radiotherapy (SBRT) in medically inoperable patients with centrally located stage I non-small cell lung cancer. (Phase I) - To estimate the local control rate of SBRT at the MTD in these patients. (Phase II) Secondary - To estimate the rates of adverse events (other than dose-limiting toxicity) of ≥ grade 3 that is possibly, probably, or definitely related to treatment and that occurs within 1 year after the start of SBRT in these patients. - To estimate the rates of late adverse events (i.e., occurs > 1 year after the start of SBRT) in these patients. - To estimate the local control and progression-free and overall survival rates in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients undergo stereotactic body radiotherapy every 2 days over 1½-2 weeks [total of 5 fractions (FX)] in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed every 3 months for 2 years, then every 6 months for 2 years, then annually.
Not recruiting | Lung Cancer | Multisite
Andrea Bezjak
A Phase I/Randomized Phase II Study of Cediranib (NSC#732208) Versus Placebo in Combination With Cisplatin and Pemetrexed in Chemonaive Patients With Malignant Pleural Mesothelioma
PRIMARY OBJECTIVES: I. To establish the maximum tolerated dose (MTD) and the recommended phase II dose of cediranib maleate (cediranib) in combination with cisplatin and pemetrexed disodium (pemetrexed). (Phase I) II. To assess the safety and toxicity of the regimen. (Phase I) III. To assess whether cisplatin/pemetrexed plus cediranib as compared to cisplatin/pemetrexed plus placebo improves progression-free survival in patients with malignant pleural mesothelioma. (Phase II) IV. To compare overall survival in patients treated with cisplatin/pemetrexed plus cediranib to those treated with cisplatin/pemetrexed plus placebo. (Phase II) V. To assess the safety and toxicity profile of the regimen. (Phase II) VI. To assess response rate (confirmed and unconfirmed, complete and partial responses) and disease control rate (response or stable disease) in the subset of patients with measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. (Phase II) VII. To assess response rate and disease control rate using modified RECIST criteria for pleural tumors in the subset of patients with measurable disease by modified RECIST criteria for pleural tumors. (Phase II) VIII. To assess the rate of agreement between local and central pathology review of mesothelioma and its histologic subtypes. (Phase II) IX. To collect specimens for banking for use in future research studies. (Phase II) OUTLINE: This is a phase I dose-escalation study of cediranib maleate followed by a phase II study. PHASE I (CLOSED): Patients receive pemetrexed disodium intravenously (IV) over 10 minutes and cisplatin IV over 2 hours on day 1 and cediranib maleate orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive cediranib maleate alone PO QD in the absence of disease progression or unacceptable toxicity. PHASE II: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and cediranib maleate PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive cediranib maleate alone PO QD in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive pemetrexed disodium and cisplatin as in arm I and placebo PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive placebo alone PO QD in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for 2 years and then at 3 years.
Not recruiting | Lung Cancer | Multisite
Anne Tsao
A Phase IIa Trial of sEphB4-HSA in Combination With Anti PD-1 Antibody (Pembrolizumab, MK3475) in Patients With Non-small Cell Lung and Head/Neck Cancer
PRIMARY OBJECTIVES: I. Determine the response rate of the combination of pembrolizumab and recombinant EphB4-HSA fusion protein (sEphB4-HSA) as combination therapy. SECONDARY OBJECTIVES: I. Determine the biomarkers of response. II. Determine the unique toxicities of the combination of pembrolizumab and sEphB4-HSA. OUTLINE: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 12 weeks.
Open | Lung Cancer | Not Multisite
Jorge Nieva
View Research Profile
Phase 1/2, First-in-Human, Dose-Escalation Study of X-396 (Ensartinib) in Patients With Advanced Solid Tumors and Expansion Phase in Patients With ALK-positive Non-Small Cell Lung Cancer
This is the first study of X-396 (ensartinib) in humans and the investigational drug will be given as a once or twice daily oral dose in 28 day cycles until there is disease progression or unacceptable safety issues. X-396 will be given to small groups of patients (1 - 6) at each dose level and the patients will be observed to see if there are any adverse safety effects. As long as there are no unacceptable safety issues after 28 days, the dose of X-396 will be increased for the next group of patients. This process will continue until the maximum tolerated dose (MTD) of X-396 is reached. Once the MTD is reached, up to 170 additional patients will also be given X-396 to further determine the activity of X-396 in patients with ALK-positive non-small cell lung cancer. These additional patients will be enrolled in the following expansion cohorts: ALK TKI-naïve patients, patients that progressed on crizotinib, patients that progressed on one or more 2nd generation ALK TKIs (patients may or may not have also received prior crizotinib), including patients with asymptomatic CNS metastases.
Suspended | Lung Cancer | Multisite
A Pilot Multi-arm Study of sEphB4-HSA in Combination With Different Chemotherapy Regimens in Patients With Specific Advanced or Metastatic Solid Tumors
PRIMARY OBJECTIVES: I. To document the safety and tolerability of sEphB4-HSA (recombinant ephB4-HSA fusion protein) intravenously (IV) weekly when administered in combination with: arm A) gemcitabine (gemcitabine hydrochloride) and nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation), arm B) docetaxel, arm C) gemcitabine and cisplatin. SECONDARY OBJECTIVES: I. To describe the adverse event profile of sEphB4-HSA IV weekly when administered in combination with: arm A) gemcitabine and nab-paclitaxel, arm B) docetaxel, arm C) gemcitabine and cisplatin. II. To characterize the pharmacokinetics of sEphB4-HSA when combined with: arm A) gemcitabine and nab-paclitaxel, arm B) docetaxel, arm C) gemcitabine and cisplatin. III. To assess, in a preliminary fashion, the anti-tumor efficacy of sEphB4-HSA in combination with the various chemotherapy regimens in each of the 4 cohorts separately: Arm A cohort 1-patients with advanced pancreatic cancer; Arm B cohort 2-patients with head and neck cancer; Arm B cohort 3-patients with non-small cell lung cancer; Arm C cohort 3: patients with cholangiocarcinoma. TERTIARY OBJECTIVES: I. To evaluate the expression of EPH receptor B4 (EphB4) and ephrinB2 in the archival tumor samples and explore potential associations with outcome. II. To bank specimens for future correlative biomarkers studies based on the results of ongoing biomarkers analyses in the phase I of sEphB4-HSA as a single agent. OUTLINE: This is a dose de-escalation study of recombinant EphB4-HSA fusion protein. Patients are assigned to 1 of 3 treatment arms. ARM A: Patients receive recombinant EphB4-HSA fusion protein IV over 1 hour on days 1, 8, 15, and 22 (beginning course 2), paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive recombinant EphB4-HSA fusion protein IV over 1 hour on days 1, 8, and 15 (beginning course 2) and docetaxel IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM C: Patients receive recombinant EphB4-HSA fusion protein IV over 1 hour on days 1, 8, and 15 (beginning course 2), cisplatin IV over 120 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. In all arms, patients with chemotherapy related toxicity may continue treatment with recombinant EphB4-HSA fusion protein alone. Patients with toxicity related to recombinant EphB4-HSA fusion protein may continue treatment with chemotherapy at the discretion of the investigator. After completion of study treatment, patients are followed up periodically.
Open | Lung Cancer | Multisite
Anthony El-Khoueiry
View Research Profile
S1013: A Prospective Study of Epidermal Growth Factor Receptor (HER-1/EGFR) Inhibitor-Induced Dermatologic Toxicity: Validation of the Functional Assessment of Cancer Therapy-EGFRI 18(FACT-EGFRI 18) Questionnaire for EGFRI-Induced Skin Toxicities
OBJECTIVES: Primary - To establish psychometric properties for the Functional Assessment of Cancer Therapy Epidermal Growth Factor Receptor Inhibitor (FACT-EGFRI 18) module (based on criterion validity, known group's validity, internal consistency reliability, and responsiveness to change) as a patient-reported outcome (PRO) measure of EGFRI-induced skin-related toxicity. Secondary - To document minimally important differences over time for the FACT-EGFRI 18 by comparing mean changes in this PRO measure to the patient's direct assessment of change using two anchor items (change in skin condition severity and impact). - To examine the association between toxicity profiles (severity and time to onset), and treatment profiles (e.g., delays and discontinuation) and the FACT-EGFRI 18 scores. - To assess degree of concordance between FACT-EGFRI 18 ratings and study site physician CTCAE Version 4.0 EGFRI-Induced Dermatologic Toxicity Grading Assessment ratings. - To evaluate feasibility outcomes. OUTLINE: This is a multicenter study. Patients complete the S1013 Functional Assessment of Cancer Therapy Epidermal Growth Factor Receptor Inhibitor (FACT-EGFRI 18) at baseline and prior to beginning therapy and clinical assessment. Patients also complete FACT-EGFRI 18 and the Changes in Skin Symptoms on days 1*, 8**, 15, 22, 29, 36, 43, 71, 99, and 127. Patients who do not develop any grade of papulopustular rash within 42 days are removed from study. Investigators performing the patients' clinical assessment complete the EGFRI-Induced Dermatologic Toxicity Grading Assessment on days 1, 8, 15, 22, 29, 36, 43, 71, 99, and 127, and the Treatment Form assessment on days 22, 43, 71, 99, and 127. Nurses or clinical trial administrators (CRA) also complete the S1013 Cover Sheet for Patient Complete Questionnaires accompanying the FACT-EGFRI 18 patients' questionnaires at each schedule assessment. NOTE: *Patients start EGFRI therapy. NOTE: **Change in Skin Symptoms questionnaire starts on Day 8.
Not recruiting | Colon / Rectal Cancer | Multisite
Laurence Baker
Molecular Analysis for Therapy Choice (MATCH)
PRIMARY OBJECTIVES: I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma. SECONDARY OBJECTIVES: I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma. II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms. IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens. OUTLINE: STEP 0 (Screening): Patients undergo biopsy along with molecular characterization of the biopsy material for specific, pre-defined mutations, amplifications, or translocations of interest via tumor sequencing and immunohistochemistry. Consenting patients also undergo collection of blood samples for research purposes. STEPS 1, 3, 5, 7 (Treatment): Patients are assigned to 1 of 35 treatment subprotocols based on molecularly-defined subgroup. (See Arms Section) STEPS 2, 4, 6 (Screening): Patients experiencing disease progression on the prior Step treatment or who could not tolerate the assigned treatment undergo review of their previous biopsy results to determine if another treatment is available or undergo another biopsy. Patients may have a maximum of 2 screening biopsies and 2 treatments per biopsy. STEP 8 (Optional Research): Consenting patients undergo end-of-treatment biopsy and collection of blood samples for research purposes. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 1 year.
Open | Breast Cancer | Multisite
Keith Flaherty
Maintenance Systemic Therapy Versus Local Consolidative Therapy (LCT) Plus Maintenance Systemic Therapy for Limited Metastatic Non-Small Cell Lung Cancer (NSCLC): A Randomized Phase II/III Trial
PRIMARY OBJECTIVES: Phase II To evaluate the impact of adding local consolidative therapy (LCT) to maintenance systemic therapy versus maintenance systemic therapy alone on progression-free survival for patients with metastatic non-small cell lung cancer (NSCLC) with no evidence of progression and limited metastatic sites after first-line systemic therapy. Phase III To evaluate the impact of adding LCT to maintenance systemic therapy versus maintenance systemic therapy alone on overall survival for patients with metastatic NSCLC with no evidence of progression and limited metastatic sites after first-line systemic therapy. SECONDARY OBJECTIVES: I. To evaluate the impact of adding LCT to maintenance systemic therapy versus maintenance systemic therapy alone on in-field local failure. II. To evaluate the impact of adding LCT to maintenance systemic therapy versus maintenance systemic therapy alone on the time to development of new lesions. III. To evaluate the impact of adding LCT to maintenance systemic therapy versus maintenance systemic therapy alone on toxicity. IV. To evaluate the impact of adding LCT to maintenance systemic therapy versus maintenance systemic therapy alone on duration of maintenance systemic therapy usage. V. To evaluate the effect of adding LCT to systemic therapy in limited stage IV NSCLC on Quality of Life (QOL) VI. To collect biospecimens and evaluate the correlation between clinical outcomes and circulating tumor DNA (ctDNA). OUTLINE: Patients are randomized into 1 of 2 arms. ARM 1 (CHEMOTHERAPY ALONE): ): Patients may receive docetaxel intravenously (IV) over 60 minutes on Day 1, erlotinib hydrochloride orally (PO) once daily (QD), or gemcitabine IV over 30 minutes on Days 1 and 8. Patients with non-squamous non-small cell lung cancer may receive pemetrexed disodium IV over 10 minutes on Day 1 alone or in combination with pembrolizumab IV over 30 minutes. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM 2 (SBRT AND CHEMOTHERAPY): Patients undergo LCT over 2-4 weeks. If LCT cannot be used to treat primary disease sites, patients also undergo intensity-modulated radiation therapy (IMRT) or 3-dimensional conformal radiation therapy (3DCRT) over 3-5 weeks. Within 2 weeks after completion of radiation therapy, patients receive chemotherapy as in Arm 1. Patients may possibly undergo surgery. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, then annually thereafter.
Open | Lung Cancer | Multisite
Puneeth Iyengar
A Randomized, Double-Blind, Placebo-Controlled Pilot Study of an Oral, Selective Peripheral Opioid Receptor Antagonist in Advanced Non-Small Cell Lung Cancer
PRIMARY OBJECTIVES: I. To determine feasibility and safety of long-term administration of two doses of a peripheral opioid receptor antagonist in patients with advanced non-small cell lung cancer (NSCLC) receiving first-line systemic therapy. SECONDARY OBJECTIVES: I. To explore whether patients randomized to one or both of the two study drug arms have less decline in health-related quality of life (HRQoL) than patients randomized to placebo. II. To estimate the difference in the pain levels and opioid/non-opioid analgesic requirements between patients receiving naloxegol or placebo. III. To estimate the difference in the adverse peripheral effects of opioids (e.g. constipation, nausea/emesis, dry mouth and urinary retention) between patients receiving naloxegol or placebo. IV. To explore whether there is a signal that naloxegol may be associated with longer progression-free survival (PFS) and overall survival (OS). V. To evaluate the difference in discontinuation rate of systemic therapy due to adverse events (AEs) and deaths attributable to systemic therapy. After completion of study treatment, patients are followed up every 3 months.
Open | Lung Cancer | Multisite
Pankaj Gupta
Powered by SC CTSI