Irinotecan in Treating Patients With Colorectal Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of irinotecan in treating patients who have colorectal cancer.

Detailed Description
-----------------
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.

Official Title
-----------------
UGT1A1 Polymorphism in Patients With Colorectal Cancer Treated With CPT-11 (Irinotecan)

Conditions
-----------------
Colorectal Cancer

Intervention / Treatment
-----------------
* Drug: irinotecan hydrochloride
* Genetic: mutation analysis
* Genetic: polymorphism analysis


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: irinotecan hydrochloride|nan|
|Genetic: mutation analysis|nan|
|Genetic: polymorphism analysis|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer