Retrospective Analysis of a Drug-Metabolizing Genotype in Cancer Patients and Correlation With Pharmacokinetic and Pharmacodynamics Data

Completed

• Conditions: Prostate Cancer; Breast Cancer; Melanoma; Cutaneous T-Cell Lymphoma; Lung Cancer

• Registration Number: NCT00341939
• Lead Sponsor: National Cancer Institute (NCI)

Brief Summary

This study is a retrospective one, exploring the hypothesis that a person's genotypic makeup may be associated with a clinical response or toxic effect to a drug. Genetic polymorphisms, that is, states of being able to assume different forms, that are in drug-metabolizing enzymes, transporters, and receptors may affect a patient's response to drug therapy. To date, there have been limited studies looking at a drug-metabolizing genotype (genetic makeup) or phenotype (result of the genotype's interaction with the environment). However, it is often wondered if the variations in a drug's action, that is, pharmacokinetic effect, come from the genotype phenotype relationship.

Participants who entered previous clinical trials at the National Cancer Institute, as approved by the Central Institutional Review Board, may be eligible for this study. Studies for which pharmacokinetic analyses were or are being performed will be the source of the patient population.

Genotyping experiments will be performed through genomic DNA isolated from stored frozen serum. The genotyping results will be compared with pharmacokinetic data and clinical outcomes. Clinical data will consist of what is obtained during the course of the principal pharmacokinetic study. The results of the retrospective analyses will provide no direct benefit to the participants.

Detailed Description

Background

Genetic polymorphisms in drug-metabolizing enzymes, transporters/receptors, and transcription factors might affect an individual s response to drug therapy.

Inter-individual differences in efficacy and toxicity of cancer chemotherapy are especially important given the narrow therapeutic index of these drugs.

During analysis of investigational agents, inter-individual variances in pharmacokinetics and pharmacodynamics are often noted. It is often wondered if these variances might in part be explained by genetic differences in drug metabolizing enzymes, transporters, or other critical regulators of gene expression.

Objectives

To better understand the genotype-phenotype relationship, additional analysis correlating pharmacokinetic data with relevant genotyping.

Eligibility

All individuals previously enrolled on IRB approved clinical trials at the National Cancer Institute.

Design

In these retrospective studies, the association between an individual s pharmacokinetic profile and the genetic variation in their drug metabolizing enzymes and other critical regulators of gene expression will be investigated.

The hypothesis that an individual s genotypic constitution may be associated with clinical response and/or toxicity will be explored.

Study Timeline

• Study Start: 2004-09-07
• Study First Submitted: 2006-06-19
• Study First Submitted QC: 2006-06-19
• Study First Posted: 2006-06-21
• Status Verified: 2024-06
• Primary Completion: 2024-06-12
• Study Completion: 2024-06-12
• Last Update Submitted: 2024-06-12
• Last Update Posted: 2024-06-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 484

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Evaluate the association between pharmacokinetic data and polymorphisms in drug-metabolizing enzymes and transporters	duration of study	To retrospectively evaluate the association between pharmacokinetic data and polymorphisms in drug-metabolizing enzymes and transporters

Secondary Outcome Measures

Name	Time	Method
Evaluate the variability in toxicity and/or response to anticancer agents	duration of study	To retrospectively evaluate the variability in toxicity and/or response to anticancer agents (phenotype)
Evaluate the association between new and previously identified polymorphisms (genotypes) in drug metabolism, drug targets and genes that might affect drug response	duration of study	To retrospectively evaluate the association between new and previously identified polymorphisms (genotypes) in drug metabolism, drug targets and genes that might affect drug response

Trial Locations

Locations (1)

National Cancer Institute (NCI), 9000 Rockville Pike; 🇺🇸 Bethesda, Maryland, United States