Clinical trial NCT00003843: Irinotecan in Treating Patients With Colorectal Cancer
Official title: UGT1A1 Polymorphism in Patients With Colorectal Cancer Treated With CPT-11 (Irinotecan)
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Colorectal Cancer
Keywords: stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
Lead sponsor: California Cancer Consortium
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no

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.

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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
Study officials:
affiliation: University of Southern California
name: Heinz-Josef Lenz, MD
role: STUDY_CHAIR
References: