Combination Chemotherapy and Bevacizumab in Treating Patients With Locally Advanced, Metastatic, or Recurrent Colorectal Cancer

Recurrent Rectal Cancer Clinical Trial

Official title: A Phase III Trial of Modified FOLFOX6 Versus CAPOX, With Bevacizumab (NSC-704865) or Placebo, as First-Line Therapy in Patients With Previously Untreated Advanced Colorectal Cancer

Status Terminated

Clinical Trial Summary

Drugs used in chemotherapy, such as oxaliplatin, leucovorin, fluorouracil, and capecitabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. Combining chemotherapy with monoclonal antibody therapy may kill more tumor cells. It is not yet known which combination chemotherapy regimen with bevacizumab works better in treating colorectal cancer. This randomized phase III trial is studying giving two different combination chemotherapy regimens together with bevacizumab and comparing how well they work in treating patients with locally advanced, metastatic, or recurrent colorectal cancer

Clinical Trial Description

OBJECTIVES:

I. Compare overall survival in patients with locally advanced, metastatic, or recurrent colorectal cancer treated with fluorouracil, leucovorin calcium, oxaliplatin, and bevacizumab vs capecitabine, oxaliplatin, and bevacizumab.

II. Compare progression-free survival and time to treatment failure in patients treated with these regimens.

III. Compare the response of patients with measurable disease treated with these regimens.

IV.Compare toxicity rates of these regimens in these patients. V. Compare patient-reported functional status and convenience of therapy in patients treated with these regimens.

VI. Correlate germline polymorphisms of DNA repair (e.g., ERCC-1, XRCC1, GST-P1, XPD, and ribonucleotide reductase), target enzymes (e.g., thymidylate synthase, dihydropyrimidine dehydrogenase, and thymidine phosphorylase), angiogenesis (e.g., vascular endothelial growth factor), and growth factors (e.g., epithelial growth factor receptor) with survival, progression-free survival, and toxicity from chemotherapy in patients treated with these regimens.

VII. Correlate tumor mRNA expression levels of similar DNA repair enzymes as well as enzymes involved in angiogenesis with survival and progression-free survival in patients treated with these regimens.Correlate tumor mRNA expression levels of similar target enzymes before treatment with survival, progression-free survival, and toxicity in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to Zubrod performance status (0 or 1 vs 2) and prior adjuvant therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46-48 hours beginning on day 1. Patients are further randomized to receive bevacizumab or placebo* IV over 30-90 minutes on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. NOTE: *As of 11/15/04, placebo is no longer part of treatment plan; all patients receive bevacizumab.

ARM II: Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine on days 1-15. Patients are further randomized to receive bevacizumab or placebo* as in arm I. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. NOTE: *As of 11/15/04, placebo is no longer part of treatment plan; all patients receive bevacizumab.

Patients are followed every 3 months until disease progression. After disease progression, patients are followed every 6 months for 2 years and then annually for up to 4 years after study entry.

PROJECTED ACCRUAL: A total of 2,200 patients (1,100 per treatment arm) will be accrued for this study within 3 years. ;

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Colon
• Adenocarcinoma of the Rectum
• Colorectal Neoplasms
• Rectal Neoplasms
• Recurrent Colon Cancer
• Recurrent Rectal Cancer
• Stage III Colon Cancer
• Stage III Rectal Cancer
• Stage IV Colon Cancer
• Stage IV Rectal Cancer

• NCT number: NCT00070122
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Terminated
• Phase: Phase 3
• Start date: April 2004