Genetic Trial to Study Diarrhea in Patients With Stage III Colon Cancer Who Are Receiving Chemotherapy

Alliance for Clinical Trials in Oncology

Status: Completed

Conditions: Neutropenia; Diarrhea; Colorectal Cancer

Treatments: Genetic: mutation analysis; Genetic: polymorphic microsatellite marker analysis

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT00048971

CDR0000257145 (Registry Identifier)

CALGB-60102

NCCTG-CALGB-60102

Details and patient eligibility

About

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.

Full 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.

Enrollment: 308 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

308 participants in 1 patient group

Group 1

Description:

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.

Treatment:

Genetic: polymorphic microsatellite marker analysis

Genetic: mutation analysis