Irinotecan, Fluorouracil, and Leucovorin in Treating Patients With Advanced Gastrointestinal Cancer
RATIONALE: Drugs used in chemotherapy, such as irinotecan, fluorouracil, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of irinotecan when given together with fluorouracil and leucovorin in treating patients with advanced gastrointestinal cancer.
|Anal Cancer Carcinoma of the Appendix Colorectal Cancer Esophageal Cancer Extrahepatic Bile Duct Cancer Gallbladder Cancer Gastric Cancer Gastrointestinal Carcinoid Tumor Gastrointestinal Stromal Tumor Liver Cancer Pancreatic Cancer Small Intestine Cancer||Drug: fluorouracil Drug: irinotecan hydrochloride Drug: leucovorin calcium Other: pharmacogenomic studies Other: pharmacological study||Phase 1|
|Study Design:||Allocation: Randomized
Intervention Model: Single Group Assignment
Primary Purpose: Treatment
|Official Title:||A Pharmacogenetic-Based Phase I Trial of Irinotecan, 5-Fluorouracil, and Leucovorin (FOLFIRI) in Patients With Advanced Gastrointestinal Cancer|
- Maximum tolerated dose of genotype-based dosing of FOLFIRI with or without monoclonal antibody therapy
- Response rate of genotype-based dosing in the subset of patients that has colorectal cancer
|Actual Study Start Date:||June 2008|
|Study Completion Date:||December 3, 2012|
|Primary Completion Date:||November 2010 (Final data collection date for primary outcome measure)|
- To determine the maximum tolerated dose of irinotecan hydrochloride in FOLFIRI for each respective UGT1A1 TA indel genotype grouping (group 1 [7/7, 7/8, 8/8], group 2 [6/7, 5/7, 5/8 ,6/8], and group 3 [6/6, 5/6, 5/5]).
- Determine the molecular basis of toxicity, other than UGT1A1 variants, in FOLFIRI-treated cancer patients.
- Determine the pharmacodynamic molecular profiles of cell signaling pathways associated with the development and severity of early and late specific toxicities in cancer patients treated with FOLFIRI.
OUTLINE: This is a dose-escalation study of irinotecan hydrochloride. Patients are stratified according to genotype of UGT1A1 TA indel.
- Group 1 ( TA genotype 7/7, 7/8, 8/8): Patients receive irinotecan hydrochloride IV over 90 minutes and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV bolus over 5 minutes followed by IV continuously over 46 hours on days 1-3.
- Group 2 (TA genotype 6/7, 6/7, 5/8, 6/8): Patients receive treatment as in group 1 with a higher initial dose of irinotecan hydrochloride.
- Group 3 (TA genotype 5/5, 5/6, 6/6): Patients receive treatment as in group 2. In all groups, treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Patients undergo blood collection at baseline and periodically during study for pharmacokinetics, dihydropyridine deaminase enzyme assay, and pathway expression analysis.
After completion of study treatment, patients are followed every 6 weeks for up to 2 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00654160
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Robert McWilliams, MD||Mayo Clinic|