Safety and Efficacy Study of Neratinib and Cetuximab to Treat Patients With Quadruple Wild-Type Metastatic Colorectal Cancer
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|ClinicalTrials.gov Identifier: NCT01960023|
Recruitment Status : Withdrawn (This registry was planned to report on the Phase II portion of the study. NSABP decided not to proceed with the Phase II portion of the study.)
First Posted : October 10, 2013
Last Update Posted : March 4, 2019
The FC-7 study is designed as an open label, single arm, Phase I/II dose-escalation study evaluating the combination of neratinib and cetuximab in patients with metastatic colorectal cancer primary tumor that is "quadruple wild-type " (wild-type KRAS, NRAS, BRAF, PIK3CA). The primary aim in the Phase I portion of this study is to determine the safety and tolerability of the two-drug combination. The primary aim of the Phase II part is to determine the overall objective response rate (complete and partial responses) by Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
Patients will receive concurrent therapy with cetuximab (400 mg/m2 IV loading dose followed by 250 mg/m2 IV weekly), and neratinib.
|Condition or disease||Intervention/treatment||Phase|
|Colorectal Cancer||Drug: Cetuximab Drug: Neratinib||Phase 1 Phase 2|
The neratinib dose-escalation using a 3+3 design will include 4 dose levels (120 mg, 160 mg, 200 mg, and 240 mg) as a daily oral dose. Up to 12 patients will be treated at the maximum tolerated dose (MTD).
The neratinib dose-escalation for the study will proceed on the basis of dose-limiting toxicity (DLT) during cycle 1. DLT will be defined as the occurrence of 1 or more of the following events during cycle 1: any grade diarrhea that is associated with fever or dehydration requiring IV fluids; grade 3 diarrhea lasting more than 2 days on optimal medical therapy; grade 4 diarrhea of any duration; grade 3 or 4 neutropenia associated with fever; grade 4 neutropenia lasting more than 7 days; grade 4 thrombocytopenia; grade 3 or 4 non-hematological toxicity (excluding grade 3 rash or allergic reaction/hypersensitivity); or any toxicity-related delay of more than 2 weeks to initiate cycle 2. Patients will be enrolled at the next dose level when all evaluable patients at the same dose level have completed the first treatment cycle. Enrolled patients will remain on the assigned dose level treatment until toxicity or disease progression.
The Phase II part of this study will proceed with a two-stage design with a maximum of 46 patients. Between 6 and 12 patients at the Phase I MTD level will be included in the Phase II, stage-one analysis.
Toxicity will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0.
Submission of tumor and blood samples for FC-7 correlative science studies will be a study requirement for all patients. A core biopsy procedure to procure fresh tumor samples from an accessible site of metastasis will be performed before study dose level assignment (after the patient has signed the consent form and has been screened for eligibility).
Optional biopsy samples of metastatic disease will be procured from consenting patients after Cycle 1 of treatment and at the time of disease progression.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Dose-Escalation Study Evaluating the Combination of Neratinib and Cetuximab in Patients With "Quadruple Wild-Type" (KRAS/NRAS/BRAF/PIK3CA Wild-Type) Metastatic Colorectal Cancer Resistant to Cetuximab|
|Study Start Date :||October 2013|
|Actual Primary Completion Date :||July 13, 2016|
|Actual Study Completion Date :||July 13, 2016|
Experimental: Arm 1: Cetuximab and Neratinib
Cetuximab 400 mg/m2 IV loading dose followed by weekly cetuximab 250 mg/m2 IV plus neratinib per oral daily until disease progression
400 mg/m2 IV loading dose followed by weekly cetuximab 250 mg/m2 IV until disease progression
Phase I portion of the study:
Dose level 1: 120 mg/day; Dose level 2: 160 mg/day; Dose level 3: 200 mg/day; Dose level 4: 240 mg/day
Phase II portion of the study: The recommended dose determined in the Phase I portion of the study.
- The safety and tolerability of cetuximab and neratinib during the Phase I portion of the study. [ Time Frame: From start of study therapy weekly through disease progression or end of therapy, approximately 2 years ]Number of patients experiencing dose limiting toxicities (DLT).
- Number of patients with Overall response rate (ORR)(complete response/partial response) and progression free survival (PFS) during the Phase II portion of the study [ Time Frame: From start of study through 16 weeks. ]Response as measured by RECIST 1.1 criteria.
- Progression-free survival (PFS). The time to progression and the time to progression based on tumor HER2 status. [ Time Frame: From start of study through disease progression or end of therapy, approximately 2 years ]
- Tumor measurement to determine objective tumor decrease and stable disease [ Time Frame: From start of study through desease progression or end of therapy, approximately 2 years ]Measurement of disease status by continuous tumor measurement.
- Measure molecular and genetic correlatives for neratinib and cetuximab [ Time Frame: Baseline (prior to treatment assignment), prior to therapy, after completion of cycle 1, and at disease progression approximately 2 years. ]
- The frequency and severity of adverse events to evaluate the overall toxicity in the Phase II portion of the study. [ Time Frame: From start of study therapy through 30 days after end of therapy, approximately 2 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01960023
|United States, Florida|
|University of Florida|
|Gainesville, Florida, United States, 32610|
|MD Anderson Cancer Center Orlando|
|Orlando, Florida, United States, 32806|
|United States, Idaho|
|Saint Luke's Mountain States Tumor Institute|
|Boise, Idaho, United States, 83712|
|United States, Illinois|
|Decatur Memorial Hospital|
|Decatur, Illinois, United States, 62526|
|United States, Michigan|
|Saint Joseph Mercy Hospital|
|Ann Arbor, Michigan, United States, 48106|
|Henry Ford Health System|
|Detroit, Michigan, United States, 48202|
|United States, North Carolina|
|Levine Cancer Institute|
|Charlotte, North Carolina, United States, 28204|
|Novant Health Presbyterian Medical Center|
|Charlotte, North Carolina, United States, 28204|
|United States, Pennsylvania|
|Thomas Jefferson University Hospital|
|Philadelphia, Pennsylvania, United States, 19107|
|Allegheny General Hospital|
|Pittsburgh, Pennsylvania, United States, 15215|
|University of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15232|
|Reading Hospital and Medical Center|
|West Reading, Pennsylvania, United States, 19611|
|Principal Investigator:||Norman Wolmark, MD||NSABP Foundation Inc|