Irinotecan, Fluorouracil, and Leucovorin in Treating Patients With Advanced Gastrointestinal Cancer

Phase 1

Completed

• Conditions: Extrahepatic Bile Duct Cancer; Anal Cancer; Carcinoma of the Appendix; Gastric Cancer; Gastrointestinal Carcinoid Tumor; Esophageal Cancer; Gallbladder Cancer; Gastrointestinal Stromal Tumor; Liver Cancer; Pancreatic Cancer

• Registration Number: NCT00654160
• Lead Sponsor: Mayo Clinic

Brief Summary

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.

Detailed Description

OBJECTIVES:

Primary

* 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 \[6/6, 5/6, 5/5\]).

Secondary

* 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.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study First Submitted: 2008-04-04
• Study First Submitted QC: 2008-04-04
• Study First Posted: 2008-04-07
• Study Start: 2008-06
• Primary Completion: 2010-11
• Study Completion: 2012-12-03
• Status Verified: 2016-09
• Last Update Submitted: 2017-05-23
• Last Update Posted: 2017-05-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 7

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose of genotype-based dosing of FOLFIRI with or without monoclonal antibody therapy

Secondary Outcome Measures

Name	Time	Method
Response rate of genotype-based dosing in the subset of patients that has colorectal cancer

Trial Locations

Locations (1)

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States