UGT1A1 Polymorphism in Patients With Colorectal Cancer Treated With CPT-11 (Irinotecan)
18 Years
N/A
Both
Colorectal Cancer
Trial Information
UGT1A1 Polymorphism in Patients With Colorectal Cancer Treated With CPT-11 (Irinotecan)
OBJECTIVES:
- Determine the frequency of genetic polymorphisms of UGT1 in Hispanics with colorectal
cancer.
- Determine if pharmacokinetics of irinotecan and its metabolites, SN38 and SN38G, are
associated with the genotype of UGT1 and clinical toxicity.
- Determine whether the genetic polymorphisms of UGT1 are associated with clinical
toxicity and pharmacokinetics/pharmacodynamics of irinotecan in patients with
unresectable colorectal cancer treated with irinotecan.
- Determine the response, time to progression, and survival in patients with UGT1A1
polymorphisms treated with irinotecan.
OUTLINE: Genomic DNA is isolated from blood samples from patients and analyzed for UGT1
polymorphisms. Patients are stratified according to UGT1 genotype (homozygous for wild type
vs heterozygous for abnormal allele vs homozygous for abnormal allele).
Patients receive irinotecan over 90 minutes weekly for 4 weeks. Treatment repeats every 6
weeks in the absence of disease progression or unacceptable toxicity.
PROJECTED ACCRUAL: Approximately 28 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically proven advanced or disseminated colorectal cancer
- Progressive disease on fluorouracil based chemotherapy OR
- Recurrence of disease within 12 months of adjuvant therapy with fluorouracil
- No known CNS metastases or carcinomatous meningitis
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- SWOG 0-2
Life expectancy:
- At least 12 weeks
Hematopoietic:
- Granulocyte count greater than 1500/mm^3
- Platelet count greater than 100,000/mm^3
- Hemoglobin at least 9.0 g/dL
Hepatic:
- Bilirubin no greater than 2 times upper limit of normal (ULN)
- SGOT no greater than 3 times ULN (no greater than 5 times ULN if liver involved)
Renal:
- Creatinine no greater than 2.0 mg/dL
- Calcium no greater than 12.0 mg/dL
Cardiovascular:
- No myocardial infarction within past 6 months
- No congestive heart failure requiring therapy
Neurologic:
- No severe psychiatric disorders
- No history of seizures
Other:
- No active or uncontrolled infection
- HIV negative
- No prior malignancy within past 5 years except adequately treated basal cell or
squamous cell skin cancer or carcinoma in situ of the cervix
- No uncontrolled diabetes mellitus (random blood sugar 200 mg/dL or greater)
- No other severe concurrent disease
- Not pregnant or nursing
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- See Disease Characteristics
- Prior oxaliplatin allowed
- No prior irinotecan or topotecan
Endocrine therapy:
- Not specified
Radiotherapy:
- Not specified
Surgery:
- Not specified
Other:
- No concurrent phenytoin, phenobarbital, or other antiepileptic prophylaxis
Type of Study:
Observational
Study Design:
N/A
Principal Investigator
Heinz-Josef Lenz, MD
Investigator Role:
Study Chair
Investigator Affiliation:
USC/Norris Comprehensive Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000067003
NCT ID:
NCT00003843
Start Date:
October 1998
Completion Date:
Related Keywords:
- Colorectal Cancer
- stage IV colon cancer
- stage IV rectal cancer
- recurrent colon cancer
- recurrent rectal cancer
- Colorectal Neoplasms
Name | Location |
|---|---|
| USC/Norris Comprehensive Cancer Center and Hospital | Los Angeles, California 90033-0804 |
| University of California Davis Cancer Center | Sacramento, California 95817 |
| City of Hope Comprehensive Cancer Center | Duarte, California 91010 |
