Retrospective Analysis of a Drug-Metabolizing Genotype in Cancer Patients and Correlation With Pharmacokinetic and Pharmacodynamics Data
|First Received Date ICMJE||June 19, 2006|
|Last Updated Date||April 21, 2017|
|Start Date ICMJE||September 7, 2004|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||To retrospectively evaluate the association between pharmacokinetic data and polymorphisms in drug-metabolizing enzymes and transporters [ Time Frame: Duration of study ]|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00341939 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Retrospective Analysis of a Drug-Metabolizing Genotype in Cancer Patients and Correlation With Pharmacokinetic and Pharmacodynamics Data|
|Official Title ICMJE||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.
Genetic polymorphisms in drug-metabolizing enzymes, transporterss/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 criticial regulators of gene expression.
To better understand the genotype-phenotype relationship, additional analysis correlating pharmacokinetic data with relevant genotyping.
All individuals previously enrolled on IRB approved clinical trials at the National Cancer Institute.
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 ICMJE||Observational|
|Study Design ICMJE||Observational Model: Case-Only
Time Perspective: Retrospective
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Intervention ICMJE||Not Provided|
|Study Groups/Cohorts||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Estimated Enrollment ICMJE||1587|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
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.
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.
|Ages||18 Years to 100 Years (Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00341939|
|Other Study ID Numbers ICMJE||999904279
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|Plan to Share Data||Not Provided|
|IPD Description||Not Provided|
|Responsible Party||National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )|
|Study Sponsor ICMJE||National Cancer Institute (NCI)|
|Collaborators ICMJE||Not Provided|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||October 27, 2016|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP