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

This study is ongoing, but not recruiting participants.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic Identifier:
First received: April 4, 2008
Last updated: April 19, 2016
Last verified: April 2016

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.

Condition Intervention Phase
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 Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Pharmacogenetic-Based Phase I Trial of Irinotecan, 5-Fluorouracil, and Leucovorin (FOLFIRI) in Patients With Advanced Gastrointestinal Cancer

Resource links provided by NLM:

Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Maximum tolerated dose of genotype-based dosing of FOLFIRI with or without monoclonal antibody therapy

Secondary Outcome Measures:
  • Response rate of genotype-based dosing in the subset of patients that has colorectal cancer

Estimated Enrollment: 70
Study Start Date: June 2008
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Detailed Description:



  • 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.


Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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)
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Please refer to this study by its identifier: NCT00654160

United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Principal Investigator: Robert McWilliams, MD Mayo Clinic
  More Information

Responsible Party: Mayo Clinic Identifier: NCT00654160     History of Changes
Other Study ID Numbers: CDR0000592931
P30CA015083 ( US NIH Grant/Contract Award Number )
MC064G ( Other Identifier: Mayo Clinic Cancer Center )
NCI-2009-01216 ( Registry Identifier: CTRP )
Study First Received: April 4, 2008
Last Updated: April 19, 2016

Keywords provided by Mayo Clinic:
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

Additional relevant MeSH terms:
Pancreatic Neoplasms
Colorectal Neoplasms
Stomach Neoplasms
Liver Neoplasms
Esophageal Neoplasms
Gastrointestinal Stromal Tumors
Carcinoid Tumor
Gastrointestinal Neoplasms
Bile Duct Neoplasms
Anus Neoplasms
Gallbladder Neoplasms
Neuroendocrine Tumors
Intestinal Neoplasms
Malignant Carcinoid Syndrome
Appendiceal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Stomach Diseases
Liver Diseases
Head and Neck Neoplasms
Esophageal Diseases processed this record on April 25, 2017