NCT01960023

Safety and Efficacy Study of Neratinib and Cetuximab to Treat Patients With Quadruple Wild-Type Metastatic Colorectal Cancer

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

• Status: Withdrawn
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: NSABP Foundation Inc · Network
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Colorectal Cancer

Interventions

Type	Name	Description
DRUG	Cetuximab	400 mg/m2 IV loading dose followed by weekly cetuximab 250 mg/m2 IV until disease progression
DRUG	Neratinib	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.

Timeline

• Start date: 2013-10-01
• Primary completion: 2016-07-13
• Completion: 2016-07-13
• First posted: 2013-10-10
• Last updated: 2021-10-27

Locations

12 sites across 1 country: United States