NCT01079780

Irinotecan Hydrochloride and Cetuximab With or Without Ramucirumab in Treating Patients With Advanced Colorectal Cancer With Progressive Disease After Treatment With Bevacizumab-Containing Chemotherapy

A Randomized Phase II Study of Irinotecan and Cetuximab With or Without the Anti-Angiogenic Antibody, Ramucirumab (IMC-1121B), in Advanced, K-ras Wild-Type Colorectal Cancer Following Progression on Bevacizumab-Containing Chemotherapy

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 136 (actual)
• Sponsor: Eastern Cooperative Oncology Group · Network
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Drugs used in chemotherapy, such as irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab and ramucirumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab and ramucirumab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. It is not yet know whether giving cetuximab and irinotecan hydrochloride together is more effective with or without ramucirumab in treating colorectal cancer. PURPOSE: This randomized phase II trial is studying the side effects and how well giving cetuximab and irinotecan hydrochloride with or without ramucirumab work in treating patients with advanced colorectal cancer with progressive disease after treatment with bevacizumab-containing chemotherapy.

Detailed description

OBJECTIVES: * To evaluate the progression-free survival of patients with advanced K-ras wild-type colorectal cancer, following progression on bevacizumab-contained chemotherapy, treated with irinotecan hydrochloride and cetuximab with versus without ramucirumab as second-line therapy. * To evaluate the response rate in patients treated with these regimens. * To evaluate the grade 3-4 toxicity rates of these regimens in these patients. * To evaluate the overall survival of patients treated with these regimens. OUTLINE: This is a multicenter, randomized study. Patients are stratified according to performance status (0 vs 1), discontinuation of oxaliplatin before disease progression (yes vs no), and time to disease progression since last treatment (≤ 6 months vs \> 6 months). Patients are randomized to 1 of 2 treatment arms. * Arm A: Patients receive cetuximab IV over 60-120 minutes and irinotecan hydrochloride over 60-90 minutes on day 1. * Arm B: Patients receive ramucirumab IV over 60 minutes on day 1 and cetuximab and irinotecan hydrochloride as in arm A. Arm B was closed early due to excessive toxicities and Arm C was then added to the study with reduced dose of protocol drugs. * Arm C: Patients receive reduced dose of ramucirumab, cetuximab and irinotecan hydrochloride as in arm B. In all arms, courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed up periodically for 5 years.

Conditions

• Colorectal Cancer

Interventions

Type	Name	Description
BIOLOGICAL	cetuximab	Given IV
BIOLOGICAL	ramucirumab	Given IV
DRUG	irinotecan hydrochloride	Given IV

Timeline

• Start date: 2011-01-18
• Primary completion: 2021-02-22
• Completion: 2021-08-17
• First posted: 2010-03-03
• Last updated: 2023-06-28
• Results posted: 2022-06-10

Locations

255 sites across 1 country: United States

Regulatory

• FDA-regulated drug study