Clinical trial NCT00096278
Conditions: Colon Adenocarcinoma Stage IIA Colon Cancer AJCC v7 Stage IIB Colon Cancer AJCC v7 Stage IIC Colon Cancer AJCC v7 Stage IIIA Colon Cancer AJCC v7 Stage IIIB Colon Cancer AJCC v7 Stage IIIC Colon Cancer AJCC v7
Sponsor: National Cancer Institute (NCI)
Start date: 2004-09-15; Completion date: 2012-12-31
Enrollment: 2710 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This randomized phase III trial is studying giving oxaliplatin, leucovorin, and fluorouracil together with bevacizumab to see how well it works compared to oxaliplatin, leucovorin, and fluorouracil alone in treating patients who have undergone surgery for stage II or stage III colon cancer. Drugs used in chemotherapy, such as oxaliplatin, leucovorin, and fluorouracil, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as bevacizumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Bevacizumab may also stop the growth of tumor cells by stopping blood flow to the tumor. Giving chemotherapy together with bevacizumab may kill more tumor cells. It is not yet known whether treatment with oxaliplatin, leucovorin, and fluorouracil is more effective with or without bevacizumab in treating patients who have undergone surgery for colon cancer.

Detailed description:
PRIMARY OBJECTIVES:

I. To compare the relative efficacy of mFOLFOX6 + bevacizumab with that of mFOLFOX6 alone in prolonging disease-free survival (DFS).

SECONDARY OBJECTIVES:

I. To compare the relative efficacy of mFOLFOX6 + bevacizumab with that of mFOLFOX6 alone in prolonging survival (S).

TERTIARY OBJECTIVES:

I. To assess the persistence of proteinuria following the discontinuation of bevacizumab.

II. To correlate the development of proteinuria with clinical sequelae. III. To evaluate the risk factors for development of proteinuria. IV. To determine the effect of discontinuation of bevacizumab on hypertension. V. To estimate the incidence of delayed vascular events such as myocardia infarction, CNS ischemia, and thrombosis in patients receiving chemotherapy + bevacizumab.

VI. To assess the effect of bevacizumab on ovarian function in premenopausal women.

VII. To assess the incidence rate of immunogenicity and examine post-treatment serum levels of bevacizumab in patients receiving bevacizumab.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive adjuvant chemotherapy comprising concurrent oxaliplatin and leucovorin calcium IV over 2 hours on day 1. Patients also receive adjuvant fluorouracil IV over 2-4 minutes on day 1 followed by fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 14 days for 12 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive adjuvant oxaliplatin, leucovorin calcium, and fluorouracil as in arm I. Treatment repeats every 14 days for 12 courses in the absence of disease progression or unacceptable toxicity. After completion of adjuvant chemotherapy, patients continue to receive bevacizumab alone every 14 days for 6 months in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Arms: arm 1: Patients receive adjuvant chemotherapy comprising concurrent oxaliplatin and leucovorin calcium IV over 2 hours on day 1. Patients also receive adjuvant fluorouracil IV over 2-4 minutes on day 1 followed by fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 14 days for 12 courses in the absence of disease progression or unacceptable toxicity. arm 2: Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive adjuvant oxaliplatin, leucovorin calcium, and fluorouracil as in arm I. Treatment repeats every 14 days for 12 courses in the absence of disease progression or unacceptable toxicity. After completion of adjuvant chemotherapy, patients continue to receive bevacizumab alone every 14 days for 6 months in the absence of disease progression or unacceptable toxicity.
Interventions: intervention 1: Bevacizumab intervention 2: Fluorouracil intervention 3: Leucovorin Calcium intervention 4: Oxaliplatin
Intervention descriptions: intervention 1: Given IV intervention 2: Given IV intervention 3: Given IV intervention 4: Given IV

Protocol documents: