Stage IV Colorectal CA ALIMTA
Phase I: The primary objective of the Phase 1 portion of this study is to determine the Maximum tolerated dose and the recommended Phase 2 dose of ALIMTA plus oxaliplatin when given with folate and vitamin B-12 supplementation in the treatment of patients with unresectable, locally advanced or metastatic colorectal cancer. The Phase I component of the study will be activated for enrollment of Mayo Clinic patients only.
Phase II: The primary objective of the Phase 2 portion of this study is to determine the tumor response rates to ALIMTA plus oxaliplatin and oxaliplatin plus 5-fluorouracil and leucovorin in patients with locally advanced unresectable or Stage IV colorectal cancer that have not received prior chemotherapy for advanced disease. Patients will be randomly assigned to receive either ALIMTA plus oxaliplatin (Arm A) or Oxaliplatin plus 5-Fluorouracil and Leucovorin (Arm B). The Phase II component of the study will be activated for enrollment of patients via the Mayo Clinic Cancer Research Consortium mechanism. A comparison will be made of the side effects between regimens.
Locally Advanced Unresectable or Stage IV Colorectal Cancer
Drug: ALIMTA plus Oxaliplatin versus Oxaliplatin plus 5-Fluorouracil and Leucovorin (FOLFOX 4 Regimen)
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Dose-Finding Study and a Randomized Phase II Study of ALIMTA Plus Oxaliplatin Versus Oxaliplatin Plus 5-Fluorouracil and Leucovorin (FOLFOX 4 Regimen) in the First-Line Treatment of Patients With Locally Advanced Unresectable or Stage IV Colorectal Cancer|
- Proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated using the exact binomial distribution.
|Study Start Date:||August 2003|
|Study Completion Date:||June 2006|
|Primary Completion Date:||June 2006 (Final data collection date for primary outcome measure)|
ALIMTA, oxaliplatin, and 5-fluorouracil (alone or with leucovorin) have shown activity as single agents in the treatment of colorectal cancer. Their different mechanisms of action make the combination of ALIMTA with oxaliplatin attractive as potential first-line therapies in terms of improving response rates and overall survival in patients with metastatic colorectal cancer. Current reports of the combination of oxaliplatin and 5-FU as first-line therapies suggest that there may be advantages in combining oxaliplatin with other antifolates in the treatment of colorectal cancer. ALIMTA is an attractive candidate to replace other drugs such as 5-FU in the combinations with oxaliplatin in the treatment of locally advanced and metastatic colorectal cancer. ALIMTA has potential advantages over 5-FU when combined with oxaliplatin because it requires a single short injection and inhibits multiple targets in the folate pathway. Therefore, we propose to conduct a trial reporting the clinical effectiveness and side effects of ALIMTA plus oxaliplatin and one of the current standards of care, the FOLFOX 4 regimen (Oxaliplatin plus 5-Fluorouracil and Leucovorin).