Clinical trial NCT00048971: Genetic Trial to Study Diarrhea in Patients With Stage III Colon Cancer Who Are Receiving Chemotherapy
Official title: A Pharmacogenetic Case-Control Study of Severe Diarrhea and Life-Threatening Neutropenia in Patients Treated With Irinotecan, 5-Fluorouracil and Leucovorin
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Colorectal Cancer
Diarrhea
Neutropenia
Keywords: adenocarcinoma of the colon
stage III colon cancer
diarrhea
neutropenia
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 308
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed with adenocarcinoma of the colon and previously enrolled on CALGB-89803.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: response
timeFrame: Up to 4 years
Secondary outcomes:
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Northeast Alabama Regional Medical Center
state: Alabama
city: La Jolla
country: United States
facility: Rebecca and John Moores UCSD Cancer Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center
state: California
city: San Diego
country: United States
facility: Veterans Affairs Medical Center - San Diego
state: California
city: San Francisco
country: United States
facility: UCSF Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: Veterans Affairs Medical Center - San Francisco
state: California
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Washington
country: United States
facility: Lombardi Cancer Center of Georgetown University Medical Center
state: District of Columbia
city: Washington
country: United States
facility: Walter Reed Army Medical Center
state: District of Columbia
city: Washington
country: United States
facility: Veterans Affairs Medical Center - Washington, DC
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Broward General Medical Center
state: Florida
city: Hollywood
country: United States
facility: Memorial Regional Hospital Comprehensive Cancer Center
state: Florida
city: Miami Beach
country: United States
facility: CCOP - Mount Sinai Medical Center
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Cancer Institute
state: Florida
city: Chicago
country: United States
facility: MBCCOP - University of Illinois at Chicago
state: Illinois
city: Chicago
country: United States
facility: Veterans Affairs Medical Center - Chicago (Westside Hospital)
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Chicago
country: United States
facility: Louis A. Weiss Memorial Hospital
state: Illinois
city: River Forest
country: United States
facility: West Suburban Center for Cancer Care
state: Illinois
city: Rockford
country: United States
facility: Saint Anthony Medical Center
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Incorporated
state: Indiana
city: South Bend
country: United States
facility: CCOP - Northern Indiana CR Consortium
state: Indiana
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at University of Iowa
state: Iowa
city: Louisville
country: United States
facility: Baptist Hospital East - Louisville
state: Kentucky
city: Baltimore
country: United States
facility: Marlene and Stewart Greenebaum Cancer Center, University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Veterans Affairs Medical Center - Baltimore
state: Maryland
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center - University Campus
state: Massachusetts
city: Saint Joseph
country: United States
facility: Lakeland Medical Center - St. Joseph
state: Michigan
city: Minneapolis
country: United States
facility: Veterans Affairs Medical Center - Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Columbia
country: United States
facility: Veterans Affairs Medical Center - Columbia (Truman Memorial)
state: Missouri
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center at University of Missouri - Columbia
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center
state: Missouri
city: Saint Louis
country: United States
facility: Missouri Baptist Cancer Center
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: CCOP - Southern Nevada Cancer Research Foundation
state: Nevada
city: Las Vegas
country: United States
facility: Veterans Affairs Medical Center - Las Vegas
state: Nevada
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth Medical School
state: New Hampshire
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Buffalo
country: United States
facility: Veterans Affairs Medical Center - Buffalo
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Elmhurst
country: United States
facility: Elmhurst Hospital Center
state: New York
city: Jamaica
country: United States
facility: Queens Cancer Center of Queens Hospital
state: New York
city: Manhasset
country: United States
facility: CCOP - North Shore University Hospital
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: New York Weill Cornell Cancer Center at Cornell University
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center, NY
state: New York
city: Syracuse
country: United States
facility: State University of New York - Upstate Medical University
state: New York
city: Syracuse
country: United States
facility: Veterans Affairs Medical Center - Syracuse
state: New York
city: Syracuse
country: United States
facility: CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
state: New York
city: Asheville
country: United States
facility: Veterans Affairs Medical Center - Asheville
state: North Carolina
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center, UNC
state: North Carolina
city: Concord
country: United States
facility: NorthEast Oncology Associates
state: North Carolina
city: Durham
country: United States
facility: Veterans Affairs Medical Center - Durham
state: North Carolina
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Fayetteville
country: United States
facility: Cape Fear Valley Health System
state: North Carolina
city: Kinston
country: United States
facility: Lenoir Memorial Hospital Cancer Center
state: North Carolina
city: Pinehurst
country: United States
facility: FirstHealth Moore Regional Hospital
state: North Carolina
city: Wilmington
country: United States
facility: New Hanover Regional Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: CCOP - Southeast Cancer Control Consortium
state: North Carolina
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center at Wake Forest University
state: North Carolina
city: Fargo
country: United States
facility: Veterans Affairs Medical Center - Fargo
state: North Dakota
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital - Ohio State University
state: Ohio
city: Danville
country: United States
facility: CCOP - Geisinger Clinic and Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Western Pennsylvania Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Lifespan: The Miriam Hospital
state: Rhode Island
city: Dallas
country: United States
facility: Veterans Affairs Medical Center - Dallas
state: Texas
city: Dallas
country: United States
facility: Simmons Cancer Center at University of Texas Southwestern Medical Center - Dalas
state: Texas
city: Bennington
country: United States
facility: Green Mountain Oncology Group
state: Vermont
city: Burlington
country: United States
facility: Vermont Cancer Center at University of Vermont
state: Vermont
city: White River Junction
country: United States
facility: Veterans Affairs Medical Center - White River Junction
state: Vermont
city: Charlottesville
country: United States
facility: Martha Jefferson Hospital
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates - Norfolk
state: Virginia
city: Richmond
country: United States
facility: MBCCOP - Massey Cancer Center
state: Virginia
city: Roanoke
country: United States
facility: Oncology and Hematology Associates of Southwest Virginia, Inc.
state: Virginia
city: Huntington
country: United States
facility: St. Mary's Medical Center
state: West Virginia
city: Green Bay
country: United States
facility: CCOP - St. Vincent Hospital Cancer Center, Green Bay
state: Wisconsin
city: Rhinelander
country: United States
facility: Ministry Medical Group - Northern Region
state: Wisconsin
city: Montreal
country: Canada
facility: McGill University
state: Quebec
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico School of Medicine Medical Sciences Campus
Study officials:
affiliation: University of Chicago
name: Mark J. Ratain, MD
role: STUDY_CHAIR
References: