A Pharmacogenetic Case-Control Study of Severe Diarrhea and Life-Threatening Neutropenia in Patients Treated With Irinotecan, 5-Fluorouracil and Leucovorin
N/A
18 Years
N/A
18 Years
N/A
Not Enrolling
Both
Colorectal Cancer, Diarrhea, Neutropenia
Both
Colorectal Cancer, Diarrhea, Neutropenia
Trial Information
A Pharmacogenetic Case-Control Study of Severe Diarrhea and Life-Threatening Neutropenia in Patients Treated With Irinotecan, 5-Fluorouracil and Leucovorin
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.
PROJECTED ACCRUAL: Approximately 308 patients will be accrued for this study.
Inclusion 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
Performance status
- Not specified
Life expectancy
- Not specified
Hematopoietic
- See Disease Characteristics
Hepatic
- Not specified
Renal
- Not specified
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- See Disease Characteristics
Endocrine therapy
- Not specified
Radiotherapy
- Not specified
Surgery
- Not specified
Type of Study:
Observational
Study Design:
N/A
Principal Investigator
Mark J. Ratain, MD
Investigator Role:
Study Chair
Investigator Affiliation:
University of Chicago
Authority:
United States: Federal Government
Study ID:
CDR0000257145
NCT ID:
NCT00048971
Start Date:
April 2002
Completion Date:
Related Keywords:
- Colorectal Cancer
- Diarrhea
- Neutropenia
- adenocarcinoma of the colon
- stage III colon cancer
- diarrhea
- neutropenia
- Colonic Neoplasms
- Colorectal Neoplasms
- Diarrhea
- Neutropenia
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
| Walter Reed Army Medical Center | Washington, District of Columbia 20307-5000 |
| University of Chicago Cancer Research Center | Chicago, Illinois 60637 |
| University of Minnesota Cancer Center | Minneapolis, Minnesota 55455 |
| Lineberger Comprehensive Cancer Center, UNC | Chapel Hill, North Carolina 27599-7295 |
| Duke Comprehensive Cancer Center | Durham, North Carolina 27710 |
| Arthur G. James Cancer Hospital - Ohio State University | Columbus, Ohio 43210 |
| CCOP - Southern Nevada Cancer Research Foundation | Las Vegas, Nevada 89106 |
| CCOP - Christiana Care Health Services | Wilmington, Delaware 19899 |
| CCOP - Mount Sinai Medical Center | Miami Beach, Florida 33140 |
| Barnes-Jewish Hospital | Saint Louis, Missouri 63110 |
| CCOP - North Shore University Hospital | Manhasset, New York 11030 |
| State University of New York - Upstate Medical University | Syracuse, New York 13210 |
| CCOP - Southeast Cancer Control Consortium | Winston-Salem, North Carolina 27104-4241 |
| MBCCOP - Massey Cancer Center | Richmond, Virginia 23298-0037 |
| Mount Sinai Medical Center, NY | New York, New York 10029 |
| Comprehensive Cancer Center at Wake Forest University | Winston-Salem, North Carolina 27157-1082 |
| Western Pennsylvania Hospital | Pittsburgh, Pennsylvania 15224 |
| Green Mountain Oncology Group | Rutland, Vermont 05701 |
| Veterans Affairs Medical Center - White River Junction | White River Junction, Vermont 05009 |
| Martha Jefferson Hospital | Charlottesville, Virginia 22901 |
| MBCCOP - University of Illinois at Chicago | Chicago, Illinois 60612 |
| CCOP - Northern Indiana CR Consortium | South Bend, Indiana 46601 |
| Holden Comprehensive Cancer Center at University of Iowa | Iowa City, Iowa 52242-1002 |
| Ellis Fischel Cancer Center at University of Missouri - Columbia | Columbia, Missouri 65203 |
| CCOP - Geisinger Clinic and Medical Center | Danville, Pennsylvania 17822-2001 |
| CCOP - St. Vincent Hospital Cancer Center, Green Bay | Green Bay, Wisconsin 54301 |
| North Shore University Hospital | Manhasset, New York 11030 |
| Veterans Affairs Medical Center - Chicago (Westside Hospital) | Chicago, Illinois 60612 |
| Veterans Affairs Medical Center - San Francisco | San Francisco, California 94121 |
| Baptist Hospital East - Louisville | Louisville, Kentucky 40207 |
| CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C. | Syracuse, New York 13217 |
| Veterans Affairs Medical Center - Fargo | Fargo, North Dakota 58102 |
| Oncology and Hematology Associates of Southwest Virginia, Inc. | Roanoke, Virginia 24014 |
| Veterans Affairs Medical Center - Minneapolis | Minneapolis, Minnesota 55417 |
| Veterans Affairs Medical Center - Columbia (Truman Memorial) | Columbia, Missouri 65201 |
| University of Nebraska Medical Center | Omaha, Nebraska 68198-3330 |
| Veterans Affairs Medical Center - Buffalo | Buffalo, New York 14215 |
| Veterans Affairs Medical Center - Syracuse | Syracuse, New York 13210 |
| Veterans Affairs Medical Center - Durham | Durham, North Carolina 27705 |
| Rebecca and John Moores UCSD Cancer Center | La Jolla, California 92093-0658 |
| Broward General Medical Center | Fort Lauderdale, Florida 33316 |
| Florida Hospital Cancer Institute | Orlando, Florida 32804 |
| Marlene and Stewart Greenebaum Cancer Center, University of Maryland | Baltimore, Maryland 21201-1595 |
| Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute | Boston, Massachusetts 02115 |
| University of Massachusetts Memorial Medical Center - University Campus | Worcester, Massachusetts 01655 |
| Northeast Alabama Regional Medical Center | Anniston, Alabama 36207 |
| Veterans Affairs Medical Center - San Diego | San Diego, California 92161 |
| UCSF Comprehensive Cancer Center | San Francisco, California 94115 |
| Veterans Affairs Medical Center - Washington, DC | Washington, District of Columbia 20422 |
| Memorial Regional Hospital Comprehensive Cancer Center | Hollywood, Florida 33021 |
| Louis A. Weiss Memorial Hospital | Chicago, Illinois 60640 |
| West Suburban Center for Cancer Care | River Forest, Illinois 60305 |
| Saint Anthony Medical Center | Rockford, Illinois 61108 |
| Fort Wayne Medical Oncology and Hematology, Incorporated | Fort Wayne, Indiana 46885-5099 |
| Veterans Affairs Medical Center - Baltimore | Baltimore, Maryland 21201 |
| Lakeland Medical Center - St. Joseph | Saint Joseph, Michigan 49085 |
| Veterans Affairs Medical Center - Las Vegas | Las Vegas, Nevada 89106 |
| Cooper University Hospital | Camden, New Jersey 08103 |
| Elmhurst Hospital Center | Elmhurst, New York 11373 |
| Queens Cancer Center of Queens Hospital | Jamaica, New York 11432 |
| Veterans Affairs Medical Center - Asheville | Asheville, North Carolina 28805 |
| NorthEast Oncology Associates | Concord, North Carolina 28025 |
| Cape Fear Valley Health System | Fayetteville, North Carolina 28302-2000 |
| Lenoir Memorial Hospital Cancer Center | Kinston, North Carolina 28503-1678 |
| FirstHealth Moore Regional Hospital | Pinehurst, North Carolina 28374 |
| New Hanover Regional Medical Center | Wilmington, North Carolina 28402-9025 |
| Lifespan: The Miriam Hospital | Providence, Rhode Island 02906 |
| Veterans Affairs Medical Center - Dallas | Dallas, Texas 75216 |
| Virginia Oncology Associates - Norfolk | Norfolk, Virginia 23502 |
| St. Mary's Medical Center | Huntington, West Virginia 25701 |
| Ministry Medical Group - Northern Region | Rhinelander, Wisconsin 54501 |
| Vermont Cancer Center at University of Vermont | Burlington, Vermont 05405-0075 |
| New York Weill Cornell Cancer Center at Cornell University | New York, New York 10021 |
| Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center | Los Angeles, California 90048 |
| Norris Cotton Cancer Center at Dartmouth Medical School | Lebanon, New Hampshire 03756-0002 |
| Missouri Baptist Cancer Center | St. Louis, Missouri 63131 |
| Palm Beach Cancer Institute | West Palm Beach, Florida 33401 |
| Siteman Cancer Center | Saint Louis, Missouri 63110 |
| Lombardi Cancer Center of Georgetown University Medical Center | Washington, District of Columbia 20007 |
| Simmons Cancer Center at University of Texas Southwestern Medical Center - Dalas | Dallas, Texas 75235-9154 |
