Clinical trial NCT00499369
Conditions: Recurrent Colon Cancer Recurrent Rectal Cancer Stage IVA Colon Cancer Stage IVA Rectal Cancer Stage IVB Colon Cancer Stage IVB Rectal Cancer
Sponsor: National Cancer Institute (NCI)
Start date: 2007-06-01; Completion date: 2012-11-01
Enrollment: 72 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This randomized phase III trial is studying giving irinotecan and cetuximab together with bevacizumab to see how well it works compared with giving irinotecan and cetuximab alone in treating patients with metastatic colorectal cancer that progressed during first-line therapy. Drugs used in chemotherapy, such as irinotecan, 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 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. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether irinotecan and cetuximab are more effective with or without bevacizumab in treating metastatic colorectal cancer.

Detailed description:
PRIMARY OBJECTIVES:

I. Compare progression-free survival of patients with metastatic colorectal cancer that progressed on first-line therapy comprising bevacizumab and FOLFOX, OPTIMOX, or XELOX treated with irinotecan hydrochloride-based chemotherapy and cetuximab with vs without bevacizumab.

II. Compare overall survival of patients treated with these regimens. III. Compare objective tumor response (confirmed and unconfirmed, complete and partial response) in patients with measurable disease treated with these regimens.

IV. Compare the tolerability and safety profile of these regimens in these patients.

OUTLINE: This is a multicenter, randomized study. Patients are stratified according to Zubrod performance status (0 vs 1 or 2), discontinuation of oxaliplatin during first-line therapy (yes vs no), planned concurrent chemotherapy (FOLFIRI vs single-agent irinotecan hydrochloride), and time from last dose of bevacizumab (14-42 days vs \>= 43 days).

All patients receive 1 of the following chemotherapy regimens:

SINGLE AGENT IRINOTECAN HYDROCHLORIDE: Patients receive irinotecan hydrochloride intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

FOLFIRI: Patients receive irinotecan hydrochloride IV over 90 minutes and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46-48 hours on days 1 and 2. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.

Patients are then randomized to 1 of 3 treatment arms.

ARM I: Patients receive single-agent irinotecan hydrochloride or FOLFIRI as outlined above and cetuximab IV over 1-2 hours on day 1. Courses repeat every 14-21 days (depending upon chemotherapy regimen) in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive single-agent irinotecan hydrochloride or FOLFIRI as outlined above and cetuximab as in arm I. Patients also receive bevacizumab IV over 30 minutes on day 1. Courses repeat every 14-21 days (depending upon chemotherapy regimen) in the absence of disease progression or unacceptable toxicity.

ARM III (closed to accrual as of 4/20/2009): Patients receive single-agent irinotecan hydrochloride or FOLFIRI as outlined above and cetuximab as in arm I. Patients also receive a higher dose of bevacizumab (higher than in arm II) IV over 30 minutes on day 1. Courses repeat every 14-21 days (depending upon chemotherapy regimen) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 6 months for 2 years and then once a year for 3 years.

Arms: arm 1: Patients receive single-agent irinotecan hydrochloride IV or FOLFIRI IV. They also receive cetuximab IV over 1-2 hours on day 1. Courses repeat every 14-21 days (depending upon chemotherapy regimen) in the absence of disease progression or unacceptable toxicity. arm 2: Patients receive single-agent irinotecan hydrochloride or FOLFIRI AND cetuximab as in arm I. Patients also receive bevacizumab IV over 30 minutes on day 1. Courses repeat every 14-21 days (depending upon chemotherapy regimen) in the absence of disease progression or unacceptable toxicity. arm 3: Patients receive single-agent irinotecan hydrochloride or FOLFIRI AND cetuximab as in arm I. Patients also receive a higher dose of bevacizumab (higher than in arm II) IV over 30 minutes on day 1. Courses repeat every 14-21 days (depending upon chemotherapy regimen) in the absence of disease progression or unacceptable toxicity.
Interventions: intervention 1: irinotecan hydrochloride intervention 2: leucovorin calcium intervention 3: fluorouracil intervention 4: cetuximab intervention 5: bevacizumab
Intervention descriptions: intervention 1: Given IV intervention 2: Given IV intervention 3: Given IV intervention 4: Given IV intervention 5: Given IV

Protocol documents: