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
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
Enrollment (Actual)
Contacts and Locations
Study Locations
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Maryland
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Bethesda, Maryland, United States, 20892
- National Cancer Institute (NCI), 9000 Rockville Pike
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
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
Cohorts and Interventions
Group / Cohort |
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1/Cancer Patients
Cancer patients previously enrolled on IRB approved clinical trials at NCI
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Evaluate the association between pharmacokinetic data and polymorphisms in drug-metabolizing enzymes and transporters
Time Frame: duration of study
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To retrospectively evaluate the association between pharmacokinetic data and polymorphisms in drug-metabolizing enzymes and transporters
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duration of study
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Evaluate the variability in toxicity and/or response to anticancer agents
Time Frame: duration of study
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To retrospectively evaluate the variability in toxicity and/or response to anticancer agents (phenotype)
|
duration of study
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Evaluate the association between new and previously identified polymorphisms (genotypes) in drug metabolism, drug targets and genes that might affect drug response
Time Frame: duration of study
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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
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: William D Figg, Pharm.D., National Cancer Institute (NCI)
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 999904279
- 04-C-N279
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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