Genetic Trial to Study Diarrhea in Patients With Stage III Colon Cancer Who Are Receiving Chemotherapy

A Pharmacogenetic Case-Control Study of Severe Diarrhea and Life-Threatening Neutropenia in Patients Treated With Irinotecan, 5-Fluorouracil and Leucovorin

RATIONALE: Genetic testing may help predict how patients will respond to chemotherapy drugs and may help doctors plan more effective treatment with fewer side effects.

PURPOSE: Genetic study to determine how genes affect the severity of diarrhea in patients with stage III colon cancer who are receiving chemotherapy.

Study Overview

• Status: Completed
• Conditions: Diarrhea; Colorectal Cancer; Neutropenia
• Intervention / Treatment: Genetic: mutation analysis; Genetic: polymorphic microsatellite marker analysis

Detailed Description

OBJECTIVES:

• Determine whether the presence of a 7 allele at the UGT1A1 locus is associated with either grade 3-4 diarrhea or grade 4 neutropenia in patients with stage III colon cancer after treatment with irinotecan, fluorouracil, and leucovorin calcium.
• Determine whether polymorphisms in the TS enhancer and/or MTHFR gene are associated with grade 3-4 diarrhea in these patients after treatment with fluorouracil and leucovorin calcium.
• Determine whether polymorphisms in UGT1A1, TS, MTHFR, CYP3A4, or CYP3A5 are associated with either grade 3-4 diarrhea or grade 4 neutropenia in these patients after treatment with irinotecan, fluorouracil, and leucovorin calcium.

OUTLINE: Patients are stratified according to prior therapy (irinotecan, fluorouracil, and leucovorin calcium vs fluorouracil and leucovorin calcium) and prior toxic effects (grade 3-4 diarrhea vs grade 4 neutropenia vs grade 1 or lower diarrhea AND grade 2 or lower neutropenia).

Patients undergo collection of blood specimens for polymerase chain reaction and restriction fragment length polymorphism analysis. Genotyping assays are performed to determine UGT1A1 promoter genotyping, UGT1A1 coding polymorphisms, TS promoter polymorphisms, and MTHFR polymorphisms.

• Study Type: Observational
• Enrollment (Actual): 308

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill University
• Puerto Rico
  • San Juan, Puerto Rico, 00936-5067
    • University of Puerto Rico School of Medicine Medical Sciences Campus
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Northeast Alabama Regional Medical Center
  • California
    • La Jolla, California, United States, 92093-0658
      • Rebecca and John Moores UCSD Cancer Center
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center
    • San Diego, California, United States, 92161
      • Veterans Affairs Medical Center - San Diego
    • San Francisco, California, United States, 94115
      • UCSF Comprehensive Cancer Center
    • San Francisco, California, United States, 94121
      • Veterans Affairs Medical Center - San Francisco
  • Delaware
    • Newark, Delaware, United States, 19713
      • CCOP - Christiana Care Health Services
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Lombardi Cancer Center of Georgetown University Medical Center
    • Washington, District of Columbia, United States, 20307-5000
      • Walter Reed Army Medical Center
    • Washington, District of Columbia, United States, 20422
      • Veterans Affairs Medical Center - Washington, DC
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Broward General Medical Center
    • Hollywood, Florida, United States, 33021
      • Memorial Regional Hospital Comprehensive Cancer Center
    • Miami Beach, Florida, United States, 33140
      • CCOP - Mount Sinai Medical Center
    • Orlando, Florida, United States, 32804
      • Florida Hospital Cancer Institute
    • West Palm Beach, Florida, United States, 33401
      • Palm Beach Cancer Institute
  • Illinois
    • Chicago, Illinois, United States, 60612-7323
      • MBCCOP - University of Illinois at Chicago
    • Chicago, Illinois, United States, 60612
      • Veterans Affairs Medical Center - Chicago (Westside Hospital)
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago Cancer Research Center
    • Chicago, Illinois, United States, 60640
      • Louis A. Weiss Memorial Hospital
    • River Forest, Illinois, United States, 60305
      • West Suburban Center for Cancer Care
    • Rockford, Illinois, United States, 61108
      • Saint Anthony Medical Center
  • Indiana
    • Fort Wayne, Indiana, United States, 46885-5099
      • Fort Wayne Medical Oncology and Hematology, Incorporated
    • South Bend, Indiana, United States, 46601
      • CCOP - Northern Indiana CR Consortium
  • Iowa
    • Iowa City, Iowa, United States, 52242-1009
      • Holden Comprehensive Cancer Center at University of Iowa
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Baptist Hospital East - Louisville
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Marlene and Stewart Greenebaum Cancer Center, University of Maryland
    • Baltimore, Maryland, United States, 21201
      • Veterans Affairs Medical Center - Baltimore
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Memorial Medical Center - University Campus
  • Michigan
    • Saint Joseph, Michigan, United States, 49085
      • Lakeland Medical Center - St. Joseph
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417
      • Veterans Affairs Medical Center - Minneapolis
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Cancer Center
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Veterans Affairs Medical Center - Columbia (Truman Memorial)
    • Columbia, Missouri, United States, 65203
      • Ellis Fischel Cancer Center at University of Missouri - Columbia
    • Saint Louis, Missouri, United States, 63110
      • Barnes-Jewish Hospital
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Cancer Center
  • Nebraska
    • Omaha, Nebraska, United States, 68198-7680
      • University of Nebraska Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • CCOP - Southern Nevada Cancer Research Foundation
    • Las Vegas, Nevada, United States, 89106
      • Veterans Affairs Medical Center - Las Vegas
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756-0002
      • Norris Cotton Cancer Center at Dartmouth Medical School
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper University Hospital
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • Buffalo, New York, United States, 14215
      • Veterans Affairs Medical Center - Buffalo
    • Elmhurst, New York, United States, 11373
      • Elmhurst Hospital Center
    • Jamaica, New York, United States, 11432
      • Queens Cancer Center of Queens Hospital
    • Manhasset, New York, United States, 11030
      • CCOP - North Shore University Hospital
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center, NY
    • New York, New York, United States, 10021
      • New York Weill Cornell Cancer Center at Cornell University
    • Syracuse, New York, United States, 13210
      • State University of New York - Upstate Medical University
    • Syracuse, New York, United States, 13210
      • Veterans Affairs Medical Center - Syracuse
    • Syracuse, New York, United States, 13217
      • CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
  • North Carolina
    • Asheville, North Carolina, United States, 28805
      • Veterans Affairs Medical Center - Asheville
    • Chapel Hill, North Carolina, United States, 27599-7295
      • Lineberger Comprehensive Cancer Center, UNC
    • Concord, North Carolina, United States, 28025
      • NorthEast Oncology Associates
    • Durham, North Carolina, United States, 27705
      • Veterans Affairs Medical Center - Durham
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center
    • Fayetteville, North Carolina, United States, 28302-2000
      • Cape Fear Valley Health System
    • Kinston, North Carolina, United States, 28503-1678
      • Lenoir Memorial Hospital Cancer Center
    • Pinehurst, North Carolina, United States, 28374
      • Firsthealth Moore Regional Hospital
    • Wilmington, North Carolina, United States, 28402-9025
      • New Hanover Regional Medical Center
    • Winston-Salem, North Carolina, United States, 27104-4241
      • CCOP - Southeast Cancer Control Consortium
    • Winston-Salem, North Carolina, United States, 27157-1082
      • Comprehensive Cancer Center at Wake Forest University
  • North Dakota
    • Fargo, North Dakota, United States, 58102
      • Veterans Affairs Medical Center - Fargo
  • Ohio
    • Columbus, Ohio, United States, 43210-1240
      • Arthur G. James Cancer Hospital - Ohio State University
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822-2001
      • CCOP - Geisinger Clinic and Medical Center
    • Pittsburgh, Pennsylvania, United States, 15224
      • Western Pennsylvania Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Lifespan: The Miriam Hospital
  • Texas
    • Dallas, Texas, United States, 75216
      • Veterans Affairs Medical Center - Dallas
    • Dallas, Texas, United States, 75235-9154
      • Simmons Cancer Center at University of Texas Southwestern Medical Center - Dalas
  • Vermont
    • Bennington, Vermont, United States, 05201
      • Green Mountain Oncology Group
    • Burlington, Vermont, United States, 05401-3498
      • Vermont Cancer Center at University of Vermont
    • White River Junction, Vermont, United States, 05009
      • Veterans Affairs Medical Center - White River Junction
  • Virginia
    • Charlottesville, Virginia, United States, 22902
      • Martha Jefferson Hospital
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates - Norfolk
    • Richmond, Virginia, United States, 23298-0037
      • MBCCOP - Massey Cancer Center
    • Roanoke, Virginia, United States, 24014
      • Oncology and Hematology Associates of Southwest Virginia, Inc.
  • West Virginia
    • Huntington, West Virginia, United States, 25701
      • St. Mary's Medical Center
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • CCOP - St. Vincent Hospital Cancer Center, Green Bay
    • Rhinelander, Wisconsin, United States, 54501
      • Ministry Medical Group - Northern Region

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with adenocarcinoma of the colon and previously enrolled on CALGB-89803.

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed stage III adenocarcinoma of the colon

• Enrolled on CALGB-89803 and must fall into 1 of the following categories:

  • Received irinotecan, fluorouracil, and leucovorin calcium and experienced at least 1 of the following:

    • Grade 3-4 diarrhea
    • Grade 4 neutropenia
    • Grade 1 or lower diarrhea AND grade 2 or lower neutropenia

  • Received fluorouracil and leucovorin calcium and experienced at least 1 of the following:

    • Grade 3-4 diarrhea
    • Grade 1 or lower diarrhea AND grade 2 or lower neutropenia

PATIENT CHARACTERISTICS:

Age

• 18 and over

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1; Patients undergo collection of blood specimens for polymerase chain reaction and restriction fragment length polymorphism analysis. Genotyping assays are performed to determine UGT1A1 promoter genotyping, UGT1A1 coding polymorphisms, TS promoter polymorphisms, and MTHFR polymorphisms.	Genetic: mutation analysis; Genetic: polymorphic microsatellite marker analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
response	Up to 4 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Mark J. Ratain, MD, University of Chicago

Study record dates

Study Major Dates

• Study Start: April 1, 2002
• Primary Completion (Actual): November 1, 2006
• Study Completion (Actual): November 1, 2006

Study Registration Dates

• First Submitted: November 12, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): July 6, 2016
• Last Update Submitted That Met QC Criteria: July 1, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: adenocarcinoma of the colon; diarrhea; stage III colon cancer; neutropenia
• Additional Relevant MeSH Terms: Hematologic Diseases; Signs and Symptoms, Digestive; Agranulocytosis; Leukopenia; Leukocyte Disorders; Diarrhea; Neutropenia
• Other Study ID Numbers: CALGB-60102; NCCTG-CALGB-60102; CDR0000257145 (Registry Identifier: NCI Physician Data Query)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No