Irinotecan, Fluorouracil, and Leucovorin in Treating Patients With Advanced Gastrointestinal Cancer
Condition: 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
MeSH terms: Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms; Esophageal Neoplasms; Liver Neoplasms; Gastrointestinal Stromal Tumors; Gastrointestinal Neoplasms; Carcinoid Tumor; Anus Neoplasms; Gallbladder Neoplasms; Bile Duct Neoplasms; Cholangiocarcinoma; Malignant Carcinoid Syndrome; Intestinal Neoplasms
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): fluorouracil; irinotecan hydrochloride; leucovorin calcium; pharmacogenomic studies; pharmacological study
Intervention type(s): Drug; Drug; Drug; Other; Other
Intervention MeSH terms: Leucovorin; Fluorouracil; Irinotecan; Calcium; Levoleucovorin
Allocation: Randomized
Intervention model: Single Group Assignment
Primary purpose: Treatment
Keywords: stage IIIB anal cancer; stage IV anal cancer; recurrent anal cancer; carcinoma of the appendix; stage III colon cancer; stage IV colon cancer; recurrent colon cancer; stage III rectal cancer; stage IV rectal cancer; recurrent rectal cancer; stage III esophageal cancer; stage IV esophageal cancer; recurrent esophageal cancer; recurrent extrahepatic bile duct cancer; unresectable extrahepatic bile duct cancer; unresectable gallbladder cancer; recurrent gallbladder cancer; stage III gastric cancer; stage IV gastric cancer; recurrent gastric cancer; metastatic gastrointestinal carcinoid tumor; recurrent gastrointestinal carcinoid tumor; regional gastrointestinal carcinoid tumor; gastrointestinal stromal tumor; advanced adult primary liver cancer; localized unresectable adult primary liver cancer; recurrent adult primary liver cancer; stage II pancreatic cancer; stage III pancreatic cancer; stage IV pancreatic cancer; recurrent pancreatic cancer; recurrent small intestine cancer; small intestine adenocarcinoma; small intestine leiomyosarcoma; small intestine lymphoma