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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00654160
Recruitment Status : Completed
First Posted : April 7, 2008
Last Update Posted : May 25, 2017
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

April 4, 2008
April 7, 2008
May 25, 2017
June 2008
November 2010   (Final data collection date for primary outcome measure)
Maximum tolerated dose of genotype-based dosing of FOLFIRI with or without monoclonal antibody therapy
Maximum tolerated dose (MTD) of genotype-based dosing of FOLFIRI with or without monoclonal antibody therapy
Complete list of historical versions of study NCT00654160 on Archive Site
Response rate of genotype-based dosing in the subset of patients that has colorectal cancer
Same as current
Not Provided
Not Provided
Irinotecan, Fluorouracil, and Leucovorin in Treating Patients With Advanced Gastrointestinal Cancer
A Pharmacogenetic-Based Phase I Trial of Irinotecan, 5-Fluorouracil, and Leucovorin (FOLFIRI) in 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.



  • 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.

Phase 1
Allocation: Randomized
Intervention Model: Single Group Assignment
Primary Purpose: Treatment
  • 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
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
December 3, 2012
November 2010   (Final data collection date for primary outcome measure)


  • 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


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)


  • 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)
Sexes Eligible for Study: All
18 Years to 120 Years   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
P30CA015083 ( U.S. NIH Grant/Contract )
MC064G ( Other Identifier: Mayo Clinic Cancer Center )
NCI-2009-01216 ( Registry Identifier: CTRP )
Not Provided
Not Provided
Mayo Clinic
Mayo Clinic
National Cancer Institute (NCI)
Principal Investigator: Robert McWilliams, MD Mayo Clinic
Mayo Clinic
September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP