Bortezomib, Fluorouracil, Leucovorin, and Oxaliplatin in Treating Patients With Advanced or Metastatic Colorectal Cancer
RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It may also help the chemotherapy drugs work better by making tumor cells more sensitive to the drugs. Giving bortezomib with fluorouracil, leucovorin, and oxaliplatin may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given with fluorouracil, leucovorin, and oxaliplatin in treating patients with advanced or metastatic colorectal cancer.
|Colorectal Cancer||Drug: bortezomib Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin||Phase 1|
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of PS-341 (VELCADE) in Combination With 5FU/LV Plus Oxaliplatin in Patients With Advanced Colorectal Cancer|
- Maximum tolerated dose and recommended dose of bortezomib as measured by CTC v3.0
- Safety as measured by CTC v3.0
- Response as measured by RECIST every 8 weeks
- Time to progression as measured by Kaplan Meier and RECIST every 8 weeks
|Study Start Date:||September 2004|
|Primary Completion Date:||January 2007 (Final data collection date for primary outcome measure)|
- Determine the dose-limiting toxicity and maximum tolerated dose of bortezomib when administered with fluorouracil, leucovorin calcium, and oxaliplatin in patients with advanced or metastatic colorectal cancer.
- Determine the recommended phase II dose of bortezomib in patients treated with this regimen.
- Determine response in patients with measurable disease treated with this regimen.
OUTLINE: This is an open-label, non-randomized, multicenter, dose-escalation study of bortezomib.
Patients receive bortezomib IV over 3-5 seconds on days 1, 8, and 15; oxaliplatin IV over 2 hours on days 1 and 15; and leucovorin calcium IV over 2 hours and fluorouracil IV over 22 hours on days 1, 2, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Additional patients receive treatment at the MTD to a maximum of 12 patients at that dose level.
Patients are followed every 8 weeks until disease progression or start of a new anticancer treatment.
PROJECTED ACCRUAL: Not specified.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00098982
|Istituto Nazionale per lo Studio e la Cura dei Tumori|
|Naples, Italy, 80131|
|Centre Hospitalier Universitaire Vaudois|
|Lausanne, Switzerland, CH-1011|
|Leeds Cancer Centre at St. James's University Hospital|
|Leeds, England, United Kingdom, LS9 7TF|
|Study Chair:||Francesco Caponigro, MD||Istituto Nazionale per lo Studio e la Cura dei Tumori|