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Study Title Principal Investigator
2N-13-6 A Randomized Phase II Study of Epigenetic Priming with Azacitidine and Entinostat Prior to Nivolumab versus Nivolumab Alone in Subjects with Recurrent Metastatic Non-Small Cell Lung Cancer
Lung cancer is the most common cause of death from cancer in both men and women. Over 160,000 people in the United States died from lung cancer in 2011. Most non-small cell lung cancer(NSCLC) patients present with advanced disease. Metastatic disease is typically treated with chemotherapy alone and is considered incurable with current therapy. New, effective therapies and strategies for lung cancer are a critical need. Azacitidine is an agent that that has been shown to inhibit cancer cell growth by interfering with DNA processes for gene expression. Entinostat is an agent that inhibits cancer cell growth and promotes cell death by repressing the transfer of genetic information. Nivolumab is a monoclonal antibody (a protein that attaches to specific proteins called antigens) that has been shown to have activity against solid tumors including NSCLC. A previous study has shown that advanced lung cancer patients who have received multiple prior therapies showed responses to treatment after initial treatment with azacitidine and entinostat. The most notable responses were in those patients who received Nivolumab or a similar agent after receiving azacitidine and entinostat. In this trial, participants will receive azacitidine for injection and entinostat and then receive Nivolumab or receive Nivolumab alone. The primary objective is to evaluate the number of patients whose disease does not worsen at 32 weeks from the time of randomization. Participants will be randomized to receive either azacitidine for injection and entinostat followed by Nivolumab or Nivolumab alone. During the study, participants in both groups will have the following procedures done during each cycle: physical exam, vital signs, blood tests, performance status, assessment of side effects, review of medications, and tumor assessments with radiographic scans. All participants will stop taking study drug(s) if they do not study drugs for more than 6 weeks, their disease worsens, they have another illness which prevents them from taking the study drug(s), they cannot tolerate the side effects, pregnancy, imprisonment, they withdraw from the study, or their study doctor thinks that being on the study is no longer in their best interest. All participants will be followed every 3 months until death or for 5 years, whichever occurs first.The primary endpoint of being progression-free at 32 weeks after randomization will be assessed from baseline scans at randomization (i.e., within 4 weeks prior to starting epigenetic therapy). All participants included in the study must be assessed for response to treatment (nivolumab), even if there are major protocol treatment deviations or if they are ineligible. All participants will be evaluable for side effects from the time of their first treatment with any study therapy. Progression-free survival and overall survival will be estimated using the Kaplan-Meier method. Toxicities will be categorized for azacitidine/entinostat, and for Nivolumab, by frequency and type, and reported in tabular form.
Recruiting | Lung Cancer | Multisite
Barbara Gitlitz
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2N-15-5: 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.
Recruiting | Lung Cancer | Multisite
Barbara Gitlitz
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SWOG-S0905: 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
OBJECTIVES: I. To establish the maximum tolerated dose and the recommended phase II dose of cediranib maleate in combination with pemetrexed disodium and cisplatin in patients with malignant pleural mesothelioma. (Phase I) II. To compare the progression-free survival of patients treated with pemetrexed disodium and cisplatin with vs without cediranib maleate. (Phase II) III. To compare the overall survival of patients treated with these regimens. (Phase II) IV. To assess the safety and toxicity profile of these regimens. V. To assess the response rate (confirmed and unconfirmed, complete and partial responses) and disease control rate (responsive or stable disease) using RECIST criteria and modified RECIST criteria for pleural tumors in a subset of patients with measurable disease. (Phase II) VI. To assess the rate of agreement between local and central pathology review of mesothelioma and its histologic subtypes. (Phase II) VII. To collect specimens for banking for use in future research studies. (Phase II) OUTLINE: This is a multicenter, phase I dose-escalation study of cediranib maleate followed by a phase II randomized study. Patients enrolled in the phase II portion of the study are stratified according to Zubrod performance status (0-1 vs 2) and histologic subtype (epithelioid vs biphasic/sarcomatoid). PHASE I: Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and oral cediranib maleate once daily on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive oral cediranib maleate alone once daily 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 oral cediranib maleate once daily at the maximum tolerated dose determined in phase I on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive oral cediranib maleate alone once daily in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive pemetrexed disodium and cisplatin as in arm I and oral placebo once daily on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive oral placebo alone once daily in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed up periodically for up to 3 years.
Active, not recruiting | Lung Cancer | Multisite
Stephen Liu
2N-15-12: 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
| Lung Cancer | Multisite
Jorge Nieva
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A Phase III Double-Blind Trial for Surgically Resected Early Stage Non-Small Cell Lung Cancer: Crizotinib versus Placebo for Patients with Tumors Harboring the Anaplastic Lymphoma Kinase (ALK) Fusion Protein
This randomized phase III trial studies how well Crizotinib works and compares it to placebo in treating patients with stage IB-IIIA non-small cell lung cancer that has been removed by surgery and has a mutation in a protein called Anaplastic Lymphoma Kinase (ALK). Mutations, or changes, in ALK can make it very active and important for tumor cell growth and progression. Tumors with this mutation may respond to treatments that target the mutation, such as Crizotinib. Crizotinib may stop the growth of tumor cells by blocking the ALK protein from working. Objectives: The primary objective is to evaluate whether adjuvant therapy with Crizotinib will result in improved overall survival (OS) over placebo for patients with stage IB >= 4 cm, II and IIIA, anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) following surgical resection. Study Population: Participants 18 years and older who have undergone complete surgical resection of their stage IB ( 4 cm), II, or IIIA NSCLC and have had negative margins. N3 disease is not allowed. Study 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 receive placebo PO BID on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Follow up: After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then yearly for 5 years. Endpoint: Overall survival (OS) is defined as the time from randomization to death from any cause. Patients that have not had an event reported at analysis will be censored at their date of last follow up. Analysis: The primary analysis will include all patients who testing positive for ALK at the central reference lab (Response Genetics), however patients with a local positive test but negative central test can still be randomized on the trial and will be included in a secondary analysis. Secondary analyses will typically include the primary analysis population. Exception to this include: analysis of toxicity data, which will include all patients from the primary analysis who received study drug regardless of eligibility.
Recruiting | Lung Cancer | Multisite
Barbara Gitlitz
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Assessing the Patient Experience in Cancer Care: An Observational Communication Study
Recruiting | Brain Cancer | Multisite
Jon Tilburt
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)
Background:Combined modality therapy with chemotherapy and radiation has become the standard of care for the treatment of patients with locally advanced NSCLC.The Cancer and Leukemia Group B (CALGB) conducted a randomized Phase II study of two cycles of induction chemotherapy followed by two additional cycles of the same drugs with concomitant radiotherapy for patients with locally advanced NSCLC. The results of this trial demonstrated similar survival rates between the 2 arms.We propose to use a backbone of standard chemoradiotherapy with carboplatin and paclitaxel to investigate the addition of oral ABT-888. ABT-888 potentiates the anti-cancer effects of various cytotoxic agents including carboplatin in preclinical studies.Objectives:To establish the MTD and the recommended Phase II dose of ABT-888 when given concurrently with standard carboplatin/paclitaxel and radiotherapy in patients with unresectable Stage III non-small cell lung cancer (NSCLC).Study Population:Patients must have histologically or cytologically-proven new diagnosis of unresectable Stage IIIA/IIIB*, non-small cell lung cancer (adenocarcinoma, bronchioloalveolar cell carcinoma, large cell carcinoma, squamous cell carcinoma, or mixed). Patients age is 18 years and over.Primary Endpoints: a. Measurable disease: 1. Lesions that can be accurately measured in at least one dimension 2. Malignant lymph nodes b. Non-measurable disease: 1. All other lesions (or sites of disease), including small lesionsDescription of Study Arms:Phase I portion:First Registration: Chemoradiation Phase 6 weeks of external beam radiation + paclitaxel + carboplatin + ABT-888 at assigned dose level. Re-evaluation and Second RegistrationConsolidation Phase (ABT-888 + carboplatin + paclitaxel) (Two 21-day cycles)Phase II portion:First Registration/Randomization: Chemoradiation Phase 6 weeks of external beam radiation + paclitaxel + carboplatin + ABT-888/placebo at assigned dose level.Re-evaluation and Second Registration:ABT-888 Carboplatin Paclitaxel (2 cycles) OR Placebo Carboplatin Paclitaxel (2 cycles) Only Arm 2 will be done at USC.Intervention:Emergency unblinding will proceed in the event of an emergency or severe adverse reaction necessitating identification of the medication for the welfare of the patient.Toxicities attributable to the study regimen will undergo dose limiting. (DLT) Patient will be removed from the study for progression of disease or symptomatic deterioration, grade 3 or worse infusion reactions and unacceptable toxicity.Follow-up:All patients will be followed until death or 5 years after registration, whichever occurs first.Statistics/Analysis:This study will initially be open in limited institutions, with an expected accrual of 10-30 patients in the Phase I portion of the trial. The estimated accrual rate for this part of the study is 2-3 patients/ month. The Phase II portion of the trial will be open Group-wide. Based on data from previous studies in similar patient populations the estimated accrual rate is 8-9 patients/month for the phase II portion of the study.Primary analyses will be performed on an intent-to-treat basis. A stratified log-rank test at the 10% level will be used to test the primary hypothesis. The final analysis will take place upon the observation of 68 progression events.
Recruiting | Lung Cancer | Multisite
Barbara Gitlitz
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A Phase 1/2 Study of the Safety, Tolerability and Efficacy of Epacadostat Administered in Combination with Nivolumab in Select Advanced Cancers
Recruiting | Brain Cancer | Multisite
Heinz-Josef Lenz
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2N-16-3: 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)
| Lung Cancer | Multisite
Jorge Nieva
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2N-15-2: A Phase 2 Study of MM-121 in Combination with Docetaxel or Pemetrexed versus Docetaxel or Pemetrexed 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 that have progressed following no more than three systemic therapies for locally advanced or metastatic disease, of which one must have been an anti-PD-1 or anti-PD-L1 therapy. All patients will initially be screened for heregulin status. Eligible patients will be randomized to receive MM-121 in combination with investigator's choice of either docetaxel or pemetrexed versus docetaxel or pemetrexed alone.
Recruiting | Lung Cancer | Multisite
Jorge Nieva
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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.
Recruiting | Lung Cancer | Multisite
Julie Brahmer
2N-15-11-A Phase 3 Randomized, Open Label, Multi-Center, Global Study of MEDI4736 in combination with Tremelimumab Therapy vs Standard of Care Platinum-Based Chemotherapy in First-Line Treatment of Patients with Advanced or Metastatic Non-Small-Cell Lung cancer (NSCLC) (NEPTUNE)
Patients will be randomized in a 1:1 to receive treatment with MEDI4736 + 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.
| Lung Cancer | Multisite
Barbara Gitlitz
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2N-14-3: 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.
Withdrawn | Lung Cancer | Not Multisite
Eugene Chung
Early Diagnosis of Pulmonary Nodules Using A Plasma Proteomic Classifier
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.
Active, not recruiting | Lung Cancer | Multisite
Alex Balekian
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2O-14-1 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)
Randomization will be stratified by the type of relapse after primary treatment (sensitive or resistant/refractory disease) and presence of brain metastases.
Active, not recruiting | Lung Cancer | Multisite
Barbara Gitlitz
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SWOG-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.
Recruiting | Colon / Rectal Cancer | Multisite
Heinz-Josef Lenz
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2N-15-7: A Phase 2 Study of TH-4000 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.
Active, not recruiting | Lung Cancer | Multisite
Barbara Gitlitz
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2N-13-3 PhII-125 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.
Active, not recruiting | Lung Cancer | Multisite
Barbara Gitlitz
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2N-12-3-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
Active, not recruiting | Lung Cancer | Multisite
Barbara Gitlitz
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2L-14-1 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.
Recruiting | Lung Cancer | Multisite
Barbara Gitlitz
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2N-12-5: 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
Active, not recruiting | Lung Cancer | Multisite
Barbara Gitlitz
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2N-11-2 PhII-120 Randomized Phase II Study of AZD6244 (mitogen-activated protein kinase inhibitor) MEK-Inhibitor with erlotinib in KRAS wild type Advanced Non-Small Cell Lung Cancer (NSCLC) and a Randomized Phase II Study of AZD6244 with erlotinib in mutant KRAS Advanced NSCLC.
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.
Active, not recruiting | Lung Cancer | Multisite
Barbara Gitlitz
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0S-15-5 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.
Recruiting | Lung Cancer | Multisite
Anthony El-Khoueiry
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2N-12-2-Protocol 9090-08: 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.
Terminated | Lung Cancer | Multisite
Barbara Gitlitz
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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
Active, not recruiting | Lung Cancer | Multisite
Barbara Gitlitz
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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
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0C-16-2 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
| Lung Cancer | Multisite
Heinz-Josef Lenz
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0C-15-2: STARTRK-2 (Studies of Tumor Alterations Responsive to Targeting Receptor Kinases-2) 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
| Brain Cancer | Multisite
Barbara Gitlitz
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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 determine the efficacy of SBRT when administered at the MTD in these patients. (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) in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed periodically.
Active, not recruiting | Lung Cancer | Multisite
Quynh Nguyen
0S-15-1: A Multi-Center Study of the Brutons Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Combination with MEDI4736, in Subjects with Relapsed or Refractory Solid Tumors
Active, not recruiting | Lung Cancer | Multisite
Heinz-Josef Lenz
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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
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2N-12-6: 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.
Active, not recruiting | Lung Cancer | Multisite
Barbara Gitlitz
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2N-15-3: 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
Completed | Lung Cancer | Multisite
Jorge Nieva
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Randomized Double Blind Placebo Controlled Study of Erlotinib or Placebo in Patients with Completely Resected Epidermal Growth Factor Receptor (EGFR) Mutant Non-Small Cell Lung Cancer (NSCLC)
This is a prospective, randomized Phase III trial comparing personalized adjuvant therapy with erlotinib versus placebo in completely resected NSCLC stage IB (tumors 4 cm)-IIIA (excluding N3 disease and T1aN0M0) patients with EGFR mutation. Primary Objective: Primary objective is to determine whether adjuvant therapy with erlotinib will result in improved overall survival (OS) over placebo for patients with completely resected stage IB-IIIA patients with EGFR mutation. We hypothesize that personalized adjuvant therapy would significantly improve the overall survival in patients with resected NSCLC both for those where post-operative chemotherapy is generally not recommended and for patients after treatment with platinum based chemotherapy. Study Population: Participants, 18 years or older previously treated to A151216 with a result of EGFR exon 19 deletion or L848R mutation; Completely resected NSCLC with negative margins; complete recovery from surgery; no interstitial and fibrosis or lung disease. Study Arms: Arm 1: Treat with erlotinib at 150 mg orally once daily for up to 2 years or until disease progression or excessive toxicity. One cycle = 21 days. Arm 2: Treat with placebo at 150 mg orally once daily for up to 2 years or until disease progression or excessive toxicity. One cycle = 21 days. Follow-up: Follow-up every 6 months for 5 years following randomization. Once a patient progresses follow only for survival every 6 months. Primary endpoint: To assess whether completely resected NSCLC stage IB-IIIA patients with an EGFR mutation treated with erlotinib following complete resection have longer overall survival (OS) than patients treated with placebo alone. Analysis: The final analysis will take place once 183 deaths are observed. All analyses will be based on the intention to treat principle, and will include all randomized patients, except patients who withdraw consent prior to receiving treatment.
Recruiting | Lung Cancer | Multisite
Barbara Gitlitz
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18M-13-1 PhII-128 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
Barbara Gitlitz
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Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST)
This research trial studies genetic testing in screening patients with stage IB-IIIA non-small cell lung cancer that has been or will be removed by surgery. Studying the genes in a patient's tumor cells may help doctors select the best treatment for patients that have certain genetic changes. Objective: The primary objectives are to centrally genotype resected lung adenocarcinomas for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangements to facilitate accrual to randomized adjuvant studies, and 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). Intervention: Cytology specimen collection procedure; correlative studies; cytologic sampling; and laboratory biomarker analysis. Study Population: Participants 18 years or older with stage IB-IIIA non-small cell lung cancer. Study Methodology: Patients undergo collection of blood and tissue samples for EGFR and ALK testing via direct sequencing and fluorescence in situ hybridization (FISH). Patients that have had surgery prior to pre-registration will submit samples from the previous surgery for testing. Follow up: After completion of study, patients that are not enrolled on either A081105 or E4512 are followed up every 6 months for 5 years. Primary Endpoint: 1. Central clinical genotyping to facilitate accrual to the adjuvant Intergroup studies, E4512 and A081105, as measured by rate of accrual [ Time Frame: Up to 4 years ] 2. Feasibility of research grade FFPE tissue collection for CCG analysis, as measured by adequate specimens collected per month [ Time Frame: Up to 4 years ] Statistics: It is estimated that up to 8000 patients may need to be genotyped in order to fully accrue to the EGFR (estimated prevalence 15%) and ALK (estimated prevalence 5%) studies. Analysis: Accrual rate to the adjuvant erlotinib and crizotinib studies will be monitored every 3 months, and discussed between the study teams coordinating the ALCHEMIST study and the adjuvant studies. If accrual is inadequate, then the ALCHEMIST study will initiate strategies to improve accrual, including opening the screening study at new centers and developing strategies for genotyping at participating centers to improve catchment.
Recruiting | Lung Cancer | Multisite
Barbara Gitlitz
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Phase II/III Biomarker-Driven Master Protocol for Second Line Therapy of Squamous Cell Lung Cancer
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 (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 Response Evaluation Criteria In Solid Tumors (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 12/2015) 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 12/2015) 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: 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: 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: 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 11/2014): 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. 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.
Recruiting | Lung Cancer | Multisite
Jorge Nieva
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