NCT00098787

Bevacizumab and Oxaliplatin Combined With Irinotecan or Leucovorin and Fluorouracil in Treating Patients With Metastatic or Recurrent Colorectal Cancer

Phase II Study of Treatment Selection Based Upon Tumor Thymidylate Synthase Expression in Previously Untreated Patients With Metastatic Colorectal Cancer

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 247 (actual)
• Sponsor: Eastern Cooperative Oncology Group · Network
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, irinotecan, leucovorin, and fluorouracil, 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 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. Bevacizumab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. Giving bevacizumab together with combination chemotherapy may be a better way to block tumor growth. Studying the amount of an enzyme found in the tumor may help doctors plan the best treatment. PURPOSE: This randomized phase II trial is studying giving bevacizumab, oxaliplatin, and irinotecan or giving bevacizumab, oxaliplatin, leucovorin, and fluorouracil in treating patients with metastatic or recurrent colorectal cancer.

Detailed description

OBJECTIVES: * Compare the response rate (complete and partial), progression-free survival, and overall survival of patients with previously untreated metastatic or locally recurrent colorectal adenocarcinoma with high vs low thymidylate synthase (TS) expression treated with fluorouracil, leucovorin calcium, oxaliplatin, and bevacizumab or irinotecan, oxaliplatin, and bevacizumab. * Compare the toxicity of these regimens in these patients. * Correlate gene expression with response rates in patients treated with these regimens. * Correlate gene expression with toxicity of these regimens in these patients. * Correlate dihydropyrimidine dehydrogenase, thymidine phosphorylase, and mammalian excision repair cross complementary protein expression with antitumor response in patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to thymidylate synthase (TS) expression levels (high vs low or indeterminate). Patients with high TS expression are randomized to 1 of 2 treatment arms (Arms A or B). Patients with low or indeterminate TS expression are assigned to Arm C. * Arm A: Patients receive bevacizumab IV over 30-90 minutes followed by oxaliplatin IV over 2 hours and irinotecan IV over 90 minutes on days 1 and 15. * Arm B: Patients receive bevacizumab and oxaliplatin as in arm A, leucovorin calcium IV over 2 hours, and fluorouracil IV over 5 minutes and then continuously over 46 hours on days 1 and 15. * Arm C: Patients receive bevacizumab, oxaliplatin, leucovorin calcium, and fluorouracil as in arm B. In all arms, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Patients are followed up every 3 months for 2 years and then every 6 months for 2 years from the date of study registration.

Conditions

• Colorectal Cancer

Interventions

Type	Name	Description
BIOLOGICAL	bevacizumab	Given IV
DRUG	fluorouracil	Given IV
DRUG	irinotecan hydrochloride	Given IV
DRUG	leucovorin calcium	Given IV
DRUG	Oxaliplatin	Given IV

Timeline

• Start date: 2005-09-08
• Primary completion: 2013-11-01
• Completion: 2015-04-01
• First posted: 2004-12-09
• Last updated: 2023-07-05
• Results posted: 2014-06-27

Locations

110 sites across 1 country: United States