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

• Status: Completed
• Trial end date: 2012-12-03
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mayo Clinic
• Collaborator: National Cancer Institute (NCI)
• Treatments: Calcium; Camptothecin; Fluorouracil; Irinotecan; Leucovorin; Levoleucovorin

Criteria

DISEASE CHARACTERISTICS:

• Biopsy confirmed diagnosis of gastrointestinal cancer

• Advanced, unresectable disease

• Confirmation of UGT1A1 TA indel genotype

• Measurable or evaluable (non-measurable) disease

• Measurable disease is defined as ≥ 1 lesion that can be accurately measured (longest diameter to be recorded) as ≥ 2.0 cm with conventional techniques or as ≥ 1.0 cm with spiral CT scan

• Clinical lesions will only be considered measurable when they are superficial (e.g., skin nodules, palpable lymph nodes)

• Lesions on chest x-ray are acceptable as measurable lesions when they are clearly defined and surrounded by aerated lung

• The following are considered non-measurable disease:

• Bone lesions

• Leptomeningeal disease

• Ascites

• Pleural/pericardial effusions

• Lymphangitis cutis/ pulmonis

• Inflammatory breast disease

• Abdominal masses (not followed by CR scan or MRI)

• Cystic lesions

• All other lesions (or sites of disease), including small lesions (longest diameter < 2.0 cm with conventional techniques or as < 1.0 cm with spiral CT)

• No known central nervous system metastases or carcinomatous meningitis

PATIENT CHARACTERISTICS:

Inclusion criteria

• Life expectancy ≥ 12 weeks.

• ECOG performance status 0-2

• ANC ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

• SGOT ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN if liver metastases)

• Total Bilirubin ≤ ULN for patients in group 3 and ≤ 2.0 times ULN for patients in groups 1 and 2

• Hemoglobin ≥ 9.0 g/dL

• Creatinine ≤ 1.5 times ULN or creatinine clearance ≥ 60 mL/min

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception for the duration of study treatment

• Willing to provide blood samples for mandatory translational studies

Exclusion criteria

• Known allergy to irinotecan hydrochloride-related agents (e.g., topotecan), 5-fluorouracil, and/or leucovorin calcium

• Active or uncontrolled infection

• Evidence of serious intercurrent illness (e.g., unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia)

PRIOR CONCURRENT THERAPY:

• Recovered from all toxicities

• More than 4 weeks since prior major surgery

• More than 2 weeks since completion of prior radiotherapy

• No prior radiotherapy to > 25% of bone marrow

• More than 2 week since prior cytotoxic chemotherapy, biologic therapy, or immunotherapy

• No concurrent sargramostim (GM-CSF)