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

Retrospective Analysis of Drug Disposition and Response-related Genotypes in Cancer Patients and Correlation With Pharmacokinetics and Pharmacodynamics Data

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Melanoma; Breast Cancer; Lung Cancer; Prostate Cancer; Cutaneous T-Cell Lymphoma

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 Type: Observational
• Enrollment (Actual): 484

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Cancer Institute (NCI), 9000 Rockville Pike

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Individuals previously enrolled on IRB approved clinical trials at NCI.

Description

• INCLUSION CRITERIA:

In this retrospective study, any cancer patients entered on IRB approved clinical trials at the National Cancer Institute are eligible. Studies for which pharmacokinetic analyses were/are being performed will be the source of the patient population. At this time enrollment will be limited to patients with pharmacokinetic samples obtained during treatment on protocol 00-C-0033, 00-C-0080, 01-C-0049, 01-C-0124, 01-C-0215, 02-C-0061, 02-C-0083, 02-C-0130, 02-C-0149, 02-C-0215, 02-C-0218, 02-C-0229, 03-C-0030, 03-C-0157, 03-C-0176, 03-C-0284, 04-C-0132, 04-C-0257, 04-C-0262, 04-C-0273, 04-C-0280, 05-C-0022, 05-C-0049, 05-C-0167, 05-C-0186, 06-C-0083, 06-C-0088, 06-C-0164, 06-C-0221, 07-C-0047, 07-C-0059, 07-C-0106, 07-C-0107, 08-C-0030, 08-C-0074, 94-C-0169, 95-C-0015, 97-C-0135, 97-C-0171, and 98-C-0015.

EXCLUSION CRITERIA:

A patient will be excluded if there is an insufficient quantity of sample available to perform the genotyping procedure. This is not anticipated to be of significance for this study since the methodology does not require a large serum sample.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
1/Cancer Patients; Cancer patients previously enrolled on IRB approved clinical trials at NCI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the association between pharmacokinetic data and polymorphisms in drug-metabolizing enzymes and transporters	To retrospectively evaluate the association between pharmacokinetic data and polymorphisms in drug-metabolizing enzymes and transporters	duration of study

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: William D Figg, Pharm.D., National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: September 7, 2004
• Primary Completion: December 7, 2022
• Study Completion: December 7, 2022

Study Registration Dates

• First Submitted: June 19, 2006
• First Submitted That Met QC Criteria: June 19, 2006
• First Posted (Estimated): June 21, 2006

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 9, 2024

More Information

Terms related to this study

• Keywords: Cancer; Drug Therapy; Natural History; Pharmacokinetics; Pharmacogenetics; Pharmacodynamics
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Cutaneous
• Other Study ID Numbers: 999904279; 04-C-N279

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No