0C-14-11: A Phase 1, Open-Label, Dose Escalation Study of Pf-04518600 as a Single Agent and In Combination with PF-05082566 In Patients with Selected Locally Advanced or Metastatic Carcinomas
This is a Phase 1, open label, multi-center, multiple dose, dose escalation, safety,pharmacokinetic, and pharmacodynamic study of PF-04518600in combination with PF-05082566 . PF-04518600 and PF-05082566 are an antibodies (a type of protein) which haves been shown to stimulate the immune system.This clinical trial willinclude four parts:Participants in Parts A1 and A2 will be given PF-04518600 alone. Participants in Parts B1 and B2 will be given PF-04518600 combined with PF-05082566. Participants in Part A2 and B2 will receive doses closer to the maximum tolerated dose that has been identified in the first parts A1 and B1.
Primary objective of Monotherapy Part 1 is to assess safety, and tolerability at increasing dose levels of PF-04518600 in participants with selected advanced or metastatic solid tumors in order to establish the MTD.Primary objective of Phase 2 is to establish the Recommended Phase 2 Dose (RP2D) of PF-04518600 in participants with selected advanced or metastatic solid tumors.
Primary Objective of combination theray is to assess safety and tolerability at increasing dose levels of PF-04518600 in combination with PF-05082566 in patients with selected advanced or metastatic solid tumors and to estimate MTD of the combination.
Participants will receive doses of PF-04518600 intravenously (IV) over 60 minutes every 14 days.The initial starting dose is 0.01 mg/kg, and PF-04518600 will be given once in 14 day cycles
In Parts B1 and B2, PF-05082566 will be administered on Day 1 of every other cycle (every 28 days) per DAI as an intravenous (IV) infusion over 60 minutes (5 minutes). PF-05082566 will be administrated intravenously using a flat dose.
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
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.
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.
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
After completion of study treatment, patients are followed up periodically.
A Phase II-R and a Phase III Trial Evaluating Both *Erlotinib (PH II-R) and Chemoradiation (PH III) as Adjuvant Treatment For Patients With Resected Head of Pancreas Adenocarcinoma
I. To determine whether the addition of erlotinib (erlotinib hydrochloride) to gemcitabine
(gemcitabine hydrochloride) adjuvant chemotherapy shows a signal for improved survival as
compared to gemcitabine alone following R0 or R1 resection of head of pancreas
adenocarcinoma (including adenocarcinoma of the head, neck, and uncinate process). (Phase
II-R) II. To determine whether the use of concurrent fluoropyrimidine and radiotherapy
following adjuvant gemcitabine hydrochloride-based chemotherapy further enhances survival
for such patients who are without evidence of progressive disease after 5 cycles of
gemcitabine based chemotherapy. (Phase III)
I. To evaluate disease-free survival of adjuvant chemotherapy followed by radiotherapy and
concurrent fluoropyrimidine for patients with resected head of pancreas adenocarcinoma who
are disease free after 5 cycles of adjuvant chemotherapy.
II. To evaluate disease-free survival of standard adjuvant gemcitabine chemotherapy with and
without erlotinib for patients with resected head of pancreas adenocarcinoma.
III. To evaluate adverse events with and without erlotinib for patients with resected head
of pancreas adenocarcinoma.
IV. To evaluate adverse events of adjuvant chemotherapy with or without radiation therapy
and concurrent fluoropyrimidine for patients with resected head of pancreas adenocarcinoma
who are disease free after adjuvant chemotherapy.
V. To evaluate preoperative cross-sectional imaging of the primary head of pancreas
adenocarcinoma in order to determine the frequency with which objective criteria of
resectability are present.
VI. To determine if patients reporting low baseline fatigue, as measured by the Functional
Assessment of Chronic Illness Therapy (FACIT)-Fatigue, predicts survival and to explore
correlations between baseline fatigue, as measured by Patient-Reported Outcomes Measurement
Information System (PROMIS), and survival.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days
1, 8, and 15. Treatment repeats every 28 days for 5 courses in the absence of disease
progression or unacceptable toxicity.
ARM II: Patients receive gemcitabine hydrochloride as in arm I and erlotinib hydrochloride
orally (PO) once daily on days 1-28. Treatment repeats every 28 days for 5 courses in the
absence of disease progression or unacceptable toxicity. (NOTE: Phase II-R erlotinib
hydrochloride randomization completed, Arm 2 closed to accrual effective 2/19/2014)
Patients with no disease progression after treatment in arm I or II are then stratified
according to their first randomization treatment arm (arm I vs arm II) and randomized to 1
of 2 additional treatment arms (arm III or IV).
ARM III: Patients receive 1 course of the same treatment that they receive in arm I or II.
ARM IV: Patients receive 1 course of the same treatment that they receive in arm I or II.
Beginning within 7-21 days after completion of chemotherapy, patients undergo radiotherapy
(3-dimensional conformal radiotherapy or intensity-modulated radiotherapy) 5 days per week
for 5.5 weeks (28 fractions). During radiotherapy, patients receive either capecitabine PO
twice daily (BID) 5 days per week or fluorouracil IV continuously for 5.5 weeks or until
radiotherapy is completed.
After completion of study treatment, patients are followed up periodically.
Phase I/II Trial of Cediranib Alone or Cediranib and Lenalidomide in Iodine 131-Refractory Differentiated Thyroid Cancer
I. Determine the maximum tolerated dose (MTD) of cediranib (cediranib maleate) plus
lenalidomide. (Phase I) II. Determine the progression-free survival rates of single agent
cediranib in patients with iodine refractory, unresectable differentiated thyroid cancer
(DTC) who have evidence of disease progression within 12 months of study enrollment. (Phase
II) III. Determine the progression-free survival rates of cediranib in combination with
lenalidomide in patients with iodine refractory, unresectable DTC who have evidence of
disease progression within 12 months of study enrollment. (Phase II) IV. Compare the
progression-free survival curves of single agent cediranib to combination therapy with
cediranib with lenalidomide. (Phase II)
I. Determine the response rate of cediranib in combination with lenalidomide in patients
with iodine refractory, unresectable DTC who have evidence of disease progression within 12
months of study enrollment. (Phase I) II. Determine the toxicity, duration of response,
progression free survival, and overall survival in patients with DTC treated with cediranib
plus lenalidomide. (Phase I) III. Determine response rates and duration of response, early
tumor size changes, the toxicity, and overall survival in patients with DTC treated with
cediranib or cediranib plus lenalidomide. (Phase II) IV. Determine whether the presence of
v-raf murine sarcoma viral oncogene homolog B1 (B-RAF) or V-Ki-ras2 Kirsten rat sarcoma
(K-RAS) mutations in patients with DTC predict response to cediranib or cediranib plus
lenalidomide. (Phase II)
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
Phase I: Patients receive cediranib maleate orally (PO) once daily (QD) on days 1-28 and
lenalidomide PO QD on days 1-21 or 1-28. Courses repeat every 4 weeks in the absence of
disease progression or unacceptable toxicity.
Phase II: Patients are randomized to 1 of 2 treatment arms.
ARM A: Patients receive cediranib maleate PO QD on days 1-28. Courses repeat every 4 weeks
in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive cediranib maleate PO and lenalidomide PO as in Phase I.
After completion of study treatment, patients are followed up periodically.
7H-14-1 An Open Label, Randomized Phase 3 Clinical Trial of Nivolumab vs Therapy of Investigator's Choice in Recurrent or Metastatic Platinum-refractory Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Head and neck carcinomas (HNC) describe cancers of the upper digestive tract which include squamous cell cancers (SCCHN) of the mouth, throat, and vocal chords. At present, there is no effective standard of care that provides survival benefits beyond 4 - 6 months in second line treatment of SCCHN that spreads or returns and does not respond to platinum treatment (refractory). Nivolumab is a drug that binds to a tumor cell receptor that blocks the immune system, thus allowing the immune system to attack tumor cells. Nivolumab has demonstrated clinical activity across several tumor types, but there has been no clinical trial so far to study the clinical benefit of nivolumab in SCCHN. Cetuximab, methotrexate, and docetaxel, which appear to be the most active in the platinum refractory setting, have approved indications as single agents for treating SCCHN and will be used as the Investigator's Choice in this study. The objective of this study is to compare progression free survival (PFS) and overall survival (OS) of Nivolumab to Investigators Choice in subjects who have tumor progression within 6 months of last dose of platinum therapy.
Patients who will be enrolled for this study will have laboratory confirmed SCCHN whose disease has spread or returned within 6 months of being treated with a platinum based therapy. Participants will be randomized to receive one of the following: nivolumab, cetuximab, methotrexate, or docetaxel. During the study, participants in all groups will have the study procedures done during each cycle as stated in the protocol. All participants will stop taking study drug(s) if their disease worsens, they have another illness which prevents them from taking the study drug(s), they cannot tolerate the side effects, they withdraw from the study, their study doctor thinks that being on the study is no longer in their best interest, or the sponsor stops the study. All participants will be followed for 35 days and 80 days after stopping the study drug(s), and then every 3 months until death.
Subject characteristics including demographics, baseline performance status, disease
characteristics and baseline laboratory parameters will be summarized by randomized treatment
arm, as well as pooled across randomized treatment arm. A two-sided 0.03 log-rank test will be used to do a formal comparison of PFS across all treatment arms. Median PFS will be estimated via the Kaplan-Meier product limit method. Two-sided 95% confidence intervals (CI) for the median PFS will be computed for each randomized arm. Kaplan-Meier plots of PFS will be presented. Hazard ratios (HR) and corresponding two-sided (1-adjusted )% CI will be estimated using a Cox proportional hazards model, with treatment arm as a single covariate, stratified by the above factor, corresponding to each comparison of PFS. OS will be compared between the treatment arms among all randomized subjects using a two sided, = 0.02 level log-rank test (adjusted for interim analysis), stratified using the same factor as in PFS.
RTOG 0920 - A PHASE III STUDY OF POSTOPERATIVE RADIATION THERAPY (IMRT) +/- CETUXIMAB FOR LOCALLY-ADVANCED RESECTED HEAD AND NECK CANCER
- Determine whether the addition of cetuximab to postoperative intensity-modulated
radiotherapy (IMRT) will improve overall survival (OS) in patients with locally
advanced squamous cell carcinoma of the head and neck at intermediate risk following
- Assess the impact of the addition of cetuximab to postoperative IMRT on disease-free
survival (DFS) of these patients.
- Assess the impact of the addition of cetuximab to postoperative IMRT on acute and late
dysphagia, xerostomia, skin toxicity, and other toxicities according to common Toxicity
Criteria for Adverse Effects (CTCAE), v. 4 and their relationships with
patient-reported outcomes at 3, 12, and 24 months.
- Analyze tumor for epidermal growth factor receptor (EGFR), specifically the extent of
EGFR overexpression by immuno-histochemistry (IHC) and FISH analysis, EGFRvIII
expression, as well as the association of these assay data with OS and DFS.
- Analyze tumor for human papillomavirus (HPV) infection (as defined by in situ
hybridization), specifically, within the cohort of patients with oropharynx cancer, to
perform an exploratory analysis of the impact of HPV on DFS and OS of this patient
- Analyze tumor DNA for TP53 mutations as a predictor of response to cetuximab and
- Analyze germline DNA of polymorphic variants in EGFR intron repeats as a predictor of
response to cetuximab.
- Assess the impact of the addition of cetuximab to postoperative IMRT on loco-regional
- Assess the impact of the addition of cetuximab to postoperative IMRT on
patient-reported quality of life, swallowing, xerostomia, and skin toxicity based on
head and neck specific instruments, including the Performance Status Scale for Head and
Neck Cancer (PSS-HN), the Functional Assessment of Cancer Therapy-Head & Neck
(FACT-H&N), the University of Michigan Xerostomia-Related Quality of Life Scale
(XeQOLS), and the Dermatology Life Quality Index (DLQI).
- Assess the impact of the addition of cetuximab to postoperative IMRT on cost-utility
analysis using the EuroQol (EQ-5D).
- Evaluate the utility of image-guided radiotherapy (IGRT) as a means of enhancing the
efficacy (i.e., loco-regional control) of IMRT while reducing the acute and/or late
toxicity (particularly xerostomia) and improving patient-reported outcomes
(particularly XeQOLS scores).
- Retrospectively compare the loco-regional control rate in patients treated with IMRT
alone (no IGRT or cetuximab) with similar patients treated with external beam
radiotherapy alone in the postoperative clinical trial Radiation Therapy Oncology Group
OUTLINE: This is a multicenter study. Patients are stratified according to clinical stage
(T2-3 vs T4a), EGFR expression (high [≥ 80% of cells staining positive] vs low [< 80% of
cells staining positive] vs not evaluable), primary site of disease (oral cavity vs larynx
vs oropharynx p16+ vs oropharynx p16- vs oropharynx, p16 not evaluable), and use of
image-guided radiotherapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients undergo intensity-modulated radiotherapy (IMRT) once daily 5 days a
week for 6 weeks in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients undergo IMRT as in arm I. Patients also receive cetuximab IV over 1-2
hours once weekly beginning at least 5 days prior to the start of IMRT and continuing
for 4 weeks after the completion of IMRT (for a total of 11 doses) in the absence of
disease progression or unacceptable toxicity.
Quality of life is assessed at baseline and at 3, 12, and 24 months.
Tissue samples are collected periodically for further laboratory analysis.
After completion of study treatment, patients are followed up at 1 and 3 months, every 3
months for 2 years, every 6 months for 3 years, and then annually thereafter.
RTOG 1008: A RANDOMIZED PHASE II/III STUDY OF ADJUVANT CONCURRENT
RADIATION AND CHEMOTHERAPY VERSUS RADIATION ALONE
IN RESECTED HIGH-RISK MALIGNANT SALIVARY GLAND TUMORS
Background:Malignant tumors of the salivary gland are rare cancers that represent less than 5% of all newly diagnosed head and neck malignancies. Memorial Sloan Kettering Cancer Center reported treating 1,278 patients for malignant tumors of the salivary gland from 1939 to 1973 and identified the parotid gland followed by the submandibular glands as the most common primary sitesSurgery remains the definitive treatment of choice in patients with salivary gland malignancies without evidence of distant hematogenous metastasis. Outcomes after surgery in early stage disease are excellent. There is little high level clinical evidence to support the use of postoperative radiation. The data are limited to retrospective series that describe improved local control rates compared to surgical resection aloneHigh risk resected salivary gland malignancies represent a clinical scenario with potential for improving outcomes through multimodality therapy.Objectives:Determine the feasibility of conducting a cooperative group prospective clinical trial in patients with resected malignant salivary gland tumors; Acquire preliminary efficacy data comparing postoperative radiotherapy alone to concurrent chemotherapy and radiation using weekly cisplatin.Description of Study Arms:Arm 1: Radiation: 60-66 Gy in 2 Gy daily fractions Cisplatin: 40 mg/m weekly during radiation for 7 dosesArm 2: Radiation: 60-66 Gy in 2 Gy daily fractionsEndpoints:The primary endpoint is progression-free survival (PFS), defined by the events of local-regional progression or recurrence, distant metastasis, or death from any cause. Primary interest will focus on 2-year PFS because the recurrence/failure rate is highest during this time interval, so as to expedite the design of subsequent clinical trials in this disease.Follow-up:Follow-up: 3 months following radiation therapy. Then at months 6, 9, 12, 18, and 24 from the start of radiation for years 1 and 2, every 6 months for years 3 and 4, and then yearly for the lifetime of the subject.Statistics/Analysis:The principal comparison will be between the 2 protocol arms, since there is no prospective cooperative group experience using post-operative adjuvant radiation therapy alone in patients with resected high-risk malignant salivary gland tumors. The PFS rates for each regimen will be directly compared.
0C-14-9: A Modular Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Ascending Doses of AZD6738 in combination with Cytotoxic Chemotherapy and/or DNA Damage Repair/Novel Anti-cancer Agents in Patients with Advanced Solid Malignancies
AZD6738 is an orally dosed selective and potent inhibitor of Rad3 Related (ATR) kinase with good selectivity against other Pi3 kinase family members. ATR inhibitors are expected to cause growth inhibition in tumour cells dependent upon ATR for DNA repair. The mechanism of action of AZD6738 suggests the potential to combine it with a number of anti-cancer treatments, resulting in either synergistic or additive activity. The primary objective is evaluation of the safety, tolerability, pharmacokinetics and anti-tumour activity of AZD6738 at increasing doses, in combination with different cytotoxic chemotherapies or novel anti-cancer agents, in patients with advanced malignanciesSecondary objective is to characterise the PK and pharmacodynamics (PDc) of AZD6738 , following a single dose and at steady state after multiple dosing, when given orally in combination with cytotoxic chemotherapy and novel anti-cancer agents. The study will consist of a number of study modules, each evaluating the safety and tolerability of a specific combination agent. An oral formulation of AZD6738 will be used. The inital module will be in combination with carboplatin; the starting dose of 20mg AZD6738 BD will be escalated to reach a maximum tolerated dose in patients with advanced solid malignancies, as defined by dose-limiting toxicity. Additional modules may be added to explore potential food effects at a later date. An expansion cohort(s) in module 1 will enroll additional patients including, but not exclusive to, patients with ATM (ataxia telangiectasia mutated) deficient NSCLC (non-small cell lung cancer) adenocarcinoma, to explore further the safety, tolerability, pharmacokinetics and biological activity at selected dose(s) or alternate dosing schedules. An expansion cohort(s) in module 2 will enroll additional patients including, but not exclusive to, patients with ATM deficient gastric adenocarcinoma, to explore further the safety, tolerability, pharmacokinetics and biological activity at selected dose(s) or alternate dosing schedules. Module 2 has the following partsPart A1: AZD monotherapyPart A2: AZD + OlaparibPart B: Expansion with gastric adenocarcinomaB1: no prior T/M with PARP inhibitor,B2: Any previous treatment with a PARP inhibitorAn expansion cohort(s) in module 3 will enroll additional patients including, but not exclusive to, patients with Head and Neck Squamous Cell Carcinoma, to explore further the safety, tolerability, pharmacokinetics and biological activity at selected dose(s) or alternate dosing schedulesPrimary endpoint is safety and tolerability
A Multicenter Trial of FDG-PET/CT Staging of Head and Neck Cancer and Its Impact on the N0 Neck Surgical Treatment in Head and Neck Cancer Patients
- Determine the negative predictive value of PET/CT imaging based upon pathologic
sampling of the neck lymph nodes in patients with head and neck cancer planning to
undergo N0 neck surgery.
- Determine the potential of PET/CT imaging to change treatment.
- Estimate the sensitivity and diagnostic yield of PET/CT imaging for detecting occult
metastasis in the clinical N0 neck (both by neck and lymph node regions) or other local
- Determine the effect of other factors (e.g., tumor size, location, secondary primary
tumors, or intensity of FDG uptake) that can lead to identification of subsets of
patients that could potentially forego neck dissection or that can provide preliminary
data for subsequent studies.
- Compare the cost-effectiveness of using PET/CT imaging for staging head and neck cancer
vs current good clinical practices.
- Evaluate the incidence of occult distant body metastasis discovered by whole-body
- Correlate PET/CT imaging findings with CT/MRI findings and biomarker results.
- Evaluate the quality of life of these patients, particularly of those patients whose
management could have been altered by imaging results.
- Evaluate PET/CT imaging and biomarker data for complementary contributions to
metastatic disease prediction.
- Compare baseline PET/CT imaging and biomarker data with 2-year follow up as an adjunct
assessment of their prediction of recurrence, disease-free survival, and overall
- Determine the proportion of neck dissections that are extended (i.e., additional levels
that clinicians intend to dissect beyond the initial surgery plan) based on
local-reader PET/CT imaging findings shared with the surgeon before dissection.
- Estimate the optimum cutoff value of standardized uptake values for diagnostic accuracy
of PET/CT imaging.
- Evaluate the impact of PET/CT imaging on the N0 neck across different tumor subsites
(defined by anatomic location).
OUTLINE: This is a multicenter study.
Patients undergo fludeoxyglucose F 18-PET/CT imaging. Approximately 14 days later, patients
undergo unilateral or bilateral neck dissection.
Patients complete quality-of-life questionnaires at baseline and at 1, 12, and 24 months
Patients undergo blood and tissue sample collection periodically for biomarker analysis.
Patients are followed up periodically for up to 2 years after surgery.
0C-14-2: An Open-Label, Phase 2 Study of Neratinib in Patients with Solid Tumors with Somatic Human Epidermal Growth Factor Receptor (Egfr, Her2, Her3) Mutations or EGFR Gene Amplification
This is an open-label, non-randomized, multicenter, multinational, Phase 2 study exploring the efficacy and safety of neratinib as monotherapy or in combination with other therapies in patients with ERBB mutation-positive or EGFR gene amplified solid tumors.
Neratinib (PB-272) is a small molecule that inhibits EGFR, HER2, and HER4. Aberrant expression of EGFR, HER2, and HER3 are linked to development of many epithelial cancers including colorectal, gastric, breast and head and neck cancers. Preclinical data suggest that neratinib will have antitumor activity in EGFR- and/or HER2-expressing carcinoma cell lines.
The study will include the following cohorts of patients with tumors harboring somatic ERBB (EGFR, ERBB2, ERBB3) mutations or EGFR gene amplification.
1. Bladder/Urinary Tract
ERBB2 Mutant - Neratinib 240mg daily + Paclitaxel 80mg/m^2 IV on Days 1, 8, and 15 of every 4 week cycle
2. Biliary Tract
ERBB2 mutant HR Negative- Neratinib 240mg daily
a. ERBB2 mutant HR Negative - Neratinib 240mg daily
b. ERBB2 mutant HR Positive - Neratinib 240mg daily + Fulvestrant 500mg on Days 1, 15 of the first month, then Day 1 of every 4 week cycle
ERBB2 mutant - Neratinib 240mg daily
ERBB2 mutant - Neratinib 240mg daily
ERBB2 mutant - Neratinib 240mg daily
7. Solid tumors (NOS)
ERBB2 Mutant - Neratinib 240 mg daily
*Cohorts given combination therapy are "Combination Therapy" and all cohorts given Neratinib alone are labeled "Monotherapy."
The following cohorts have closed to accrual:
1. EGFR mutation and/or EGFR amplification
Primary brain tumors
Cohort: Primary brain tumors (glioblastoma multiforme [GBM] Grade III, glioma, gliosarcoma)
Closed to Accrual
The trial will consist of a screening period, a treatment period, safety follow-up and end of treatment (EOT) assessments, follow-up for disease progression every 8 weeks, and a survival follow-up period.
Treatment will consist of neratinib by mouth with food once daily in the morning administered on a continuous basis or combination therapy as listed above.
The primary endpoint of this study for all cohorts is to determine the objective response rate at 8 weeks (ORR8) following treatment with neratinib.
The secondary objectives of this study are:
To determine the confirmed objective response rate (ORR) according to RECIST v1.1 or other defined response criteria with neratinib monotherapy and combination therapy.
To determine the clinical benefit rate (CBR) of neratinib monotherapy and combination therapy.
To determine PFS.
To determine change in tumor growth rate for patients with primary brain tumors.
To determine the duration of response (DOR) of neratinib monotherapy and combination therapy, defined as the time from which measurement criteria are met for overall response of CR and PR until the first date of documented disease progression.
To determine overall survival (OS).
To determine the role of dual modality PET/CT scans in measuring metabolic response to neratinib monotherapy and combination therapy.
To assess the safety profile and tolerability of neratinib monotherapy and combination therapy.
To assess Patient Reported Outcomes using the EuroQol EQ-5D-5L instrument.
A Simon 2-stage optimal design will be used to determine whether neratinib has sufficient activity to warrant further development in the following cohorts: colorectal, endometrial, gastroesophageal, ovarian, and listed breast cancers. At the end of the trial, a 2-sided 80% confidence interval for Objective Response Rate will be determined for each cohort separately using the method of Koyama and Chen (2008).
Patient-related outcomes (EQ-5D-5L instrument) will be summarized and plotted over time. Changes from baseline will be provided with both point estimates and confidence intervals.
All analyses are descriptive and no formal testing is planned.
Recruiting | Any Cancer Condition or Solid Tumor | Multisite
0C-13-4: A Phase I, Open-Label, Multiple-Ascending Dose Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of avelumab (MSB0010718C) in Subjects with Metastatic or Locally Advanced Solid Tumors and Expansion to Selected Indications
This is a Phase I, open-label, dose-escalation trial with consecutive parallel group expansion in nonsmall cell lung cancer (NSCLC), metastatic breast cancer (MBC), colorectal cancer (CRC), castrate-resistant prostate cancer (CRPC), melanoma, and ovarian cancer to assess clinical activity of avelumab (MSB0010718C) .USC will participate only in the expansion part of the study. Avelumab (MSB0010718C) is an experimental drug, which belongs to a family of molecules called anti-PD-L1 antibodies. PD-L1 is a cell surface protein, found in different human tumor types, which is considered to be able to inhibit an anti-tumor response of the immune system. Compared with anti-PD-1 antibodies that target T-cells, anti-PD-L1 antibodies that target tumor cells are expected to have less side effects, including a lower risk of autoimmune-related safety issues. Based on this theory, fully human IgG1 anti-PD-L1 antibody (MSB0010718C) has been produced.Subjects will receive avelumab (MSB0010718C) intravenously as a 1-hour infusion once every 2 weeks until confirmed CR (complete response), confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP (Investigational Medical Product) occurs Expansion phase will enroll 380 subjects in total out of which 30 will be from USC. Primary objective will be to determine the safety and clinical activity of avelumab (MSB0010781C) Primary endpoint is Occurrence of DLTs during the first 3 weeks of treatment in the dose escalation part.Subjects at the end-of-treatment visit will be followed up for disease progression (CT / MRI scans every 12 weeks) up to 1 year.Descriptive statistics and graphical representations will be the main analysis tools