NCT00265850

Cetuximab and/or Bevacizumab Combined With Combination Chemotherapy in Treating Patients With Metastatic Colorectal Cancer

A Phase III Trial of Irinotecan / 5-FU / Leucovorin or Oxaliplatin / 5-FU/ Leucovorin With Bevacizumab, or Cetuximab (C225), or With the Combination of Bevacizumab and Cetuximab for Patients With Untreated Metastatic Adenocarcinoma of the Colon or Rectum

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 2,334 (actual)
• Sponsor: Alliance for Clinical Trials in Oncology · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

PURPOSE: This randomized phase III trial is studying cetuximab and/or bevacizumab when given together with combination chemotherapy to compare how well they work in treating patients with metastatic colorectal cancer. RATIONALE: Monoclonal antibodies, such as cetuximab and bevacizumab, 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 may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as fluorouracil, leucovorin, oxaliplatin, and irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving monoclonal antibodies together with combination chemotherapy may kill more tumor cells. It is not yet known whether combination chemotherapy is more effective with cetuximab and/or bevacizumab in treating patients with colorectal cancer.

Detailed description

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to physician-selected chemotherapy (FOLFOX or FOLFIRI), prior adjuvant chemotherapy (yes vs no), and prior pelvic radiotherapy (yes vs no). Patients were randomized to 1 of 3 treatment arms. Primary Objective: * To determine if the addition of cetuximab to FOLFIRI or FOLFOX chemotherapy prolongs survival compared to FOLFIRI or FOLFOX with bevacizumab in patients with untreated, advanced or metastatic colorectal cancer who have K-ras wild type tumors. Secondary Objectives: * To evaluate response, progression-free survival (PFS), time to treatment failure (TTF), and duration of response (DR) among patients with unresectable advanced metastatic colon cancer treated with bevacizumab or cetuximab in addition to chemotherapy with FOLFIRI or FOLFOX * To evaluate toxicity and, in particular, 60-day mortality among patients with unresectable advanced metastatic colon cancer treated with bevacizumab or cetuximab in addition to chemotherapy with FOLFIRI or FOLFOX * To describe patients with unresectable locally advanced or metastatic colorectal cancer rendered "resectable" with chemotherapy There are premedication guidelines that were established for patients assigned to receive cetuximab. All patients must be premedicated with diphenhydramine hydrochloride 50 mg (or a similar agent) IV prior to the first dose of cetuximab in an effort to prevent an infusion or hypersensitivity reaction. Premedication is also recommended prior to subsequent doses, but at the investigator's discretion the dose of diphenhydramine (or a similar agent) may be reduced. Pretreatment with acetaminophen may also be used. There are bevacizumab administration instructions for patients for whom surgery is being contemplated or required. For patients for whom elective surgery is contemplated, bevacizumab is to be discontinued for at least 8 weeks prior to surgery. Bevacizumab may be resumed after at least 4 weeks following surgery. Patients who undergo complete resection of metastatic disease will discontinue protocol therapy and may receive further treatment at the treating physician's discretion. For patients for whom non-elective surgery is required, hold bevacizumab as long as possible prior to surgery and for at least 6 weeks following surgery. Patients received a minimum of two cycles of therapy. Patients were allowed to receive ancillary therapy per protocol. Treatment continued until disease progression, unacceptable toxicity, or surgery with curative intent as planned. After completion of study treatment, patients are followed up to 5 years.

Conditions

• Colorectal Cancer

Interventions

Type	Name	Description
BIOLOGICAL	bevacizumab	Given IV
BIOLOGICAL	cetuximab	Given IV
DRUG	FOLFOX or	Patients receive oxaliplatin 85 mg/m\^2 IV infused over two hours followed by leucovorin 400 mg/m\^2 IV over 2 hours followed by 5-FU 400 mg/m\^2 IV bolus, then 2400 mg/m\^2 continuous IV infusion over 46-48 hours
DRUG	FOLFIRI	Patients receive irinotecan 180 mg/m\^2 IV infused over 90 minutes followed by leucovorin 400 mg/m\^2 IV over 2 hours followed by 5-FU 400 mg/m\^2 IV bolus following leucovorin then 2400 mg/m\^2 continuous IV infusion over 46-48 hours.

Timeline

• Start date: 2005-11-01
• Primary completion: 2015-02-01
• Completion: 2018-01-01
• First posted: 2005-12-15
• Last updated: 2020-05-07
• Results posted: 2017-04-26

Locations

683 sites across 2 countries: United States, Canada