NCT00720512

Second-Line Combination Chemotherapy With or Without Bevacizumab in Treating Patients With Metastatic Colorectal Cancer Who Have Received First-Line Chemotherapy and Bevacizumab

AN OPEN-LABEL, MULTICENTER, RANDOMIZED PHASE III STUDY OF SECOND-LINE CHEMOTHERAPY WITH OR WITHOUT BEVACIZUMAB IN METASTATIC COLORECTAL CANCER PATIENTS WHO HAVE RECEIVED FIRST-LINE CHEMOTHERAPY PLUS BEVACIZUMAB.

• Status: Terminated
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 184 (actual)
• Sponsor: Gruppo Oncologico del Nord-Ovest · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Drugs used in chemotherapy, such as irinotecan, oxaliplatin, 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. It is not yet known whether combination chemotherapy is more effective with or without bevacizumab in treating metastatic colorectal cancer. PURPOSE: This randomized phase III trial is studying second-line combination chemotherapy to see how well it works compared with or without bevacizumab in treating patients with metastatic colorectal cancer who have received first-line chemotherapy and bevacizumab.

Detailed description

OBJECTIVES: Primary * To compare the progression-free survival of second-line chemotherapy with or without bevacizumab in patients with metastatic colorectal cancer who have received first-line chemotherapy with bevacizumab. Secondary * To compare the overall survival, response rate, and safety profile of second-line chemotherapy of these regimens in these patients. * To conduct pharmacogenomics assessment of candidate variants in the VEGF gene and evaluate their association with progression-free survival and other study outcomes. OUTLINE: This is a multicenter study. Patients are stratified according to participating center, ECOG performance status (0 vs 1-2), disease-free interval from the last administration of first-line chemotherapy for metastatic disease (≤ 3 months vs \> 3 months), and type of second-line chemotherapy (irinotecan hydrochloride, leucovorin calcium, and fluorouracil \[FOLFIRI\] vs oxaliplatin, leucovorin calcium, and fluorouracil \[mFOLFOX-6\]). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive either irinotecan hydrochloride over 1 hour or oxaliplatin over 1 hour on day 1. Patients also receive leucovorin calcium IV over 2 hours and fluorouracil IV over 46 hours continuously beginning on day 1. * Arm II: Patients receive combination chemotherapy as in arm I and bevacizumab IV on day 1. Treatment in both arms repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. Existing formalin-fixed paraffin-embedded tumor tissue samples are assessed for pharmacogenomics and markers predictive of response, resistance to, or toxicity from bevacizumab. Samples are analyzed via RT-PCR, array comparative genomic hybridization, fluorescence in situ hybridization, sequencing of candidate genes, and immunohistochemistry. After completion of study treatment, patients are followed for 1 year.

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: 2008-06-01
• Primary completion: 2013-02-01
• Completion: 2014-03-01
• First posted: 2008-07-22
• Last updated: 2015-03-11

Locations

21 sites across 1 country: Italy