Collection of Blood From Patients With Cancer for Analysis of Genetic Differences in Drug Disposition

Trial Information

Collection of Blood From Patients With Cancer for Analysis of Genetic Differences in Drug Disposition

Background

- Genetic polymorphisms in drug-metabolizing enzymes, transporters/receptors 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 variation in
pharmacokinetics and pharmacodynamics (PK/PD) is most often noted. Genetic variation in
genes encoding proteins that regulate or mediate the metabolism and transport of drugs
often account for some of the wide variation seen in PK/PD, and ultimately the response
to, and toxicity from, anticancer agents.

Objectives

- To obtain and analyze the genomic DNA from patients with cancer on a therapeutic
clinical trial.

- To prospectively explore correlations between genetic variants involved in
inter-individual differences in drug disposition versus pharmacokinetics,
pharmacodynamics, response, and toxicity endpoints in patients receiving anticancer
agents.

- To mitigate harm due to treatment with ineffective or toxicity-inducing drugs in
patients where gene-drug interactions are established.

Eligibility

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

Design

- Exploratory study with a planned accrual of 1,000 patients

- Genomic DNA will be extracted from blood samples collected from patients (patients with
leukemia will have cheek swab samples collected) and genotyped using the Affymetrix
DMET.

- In cases where patients carry genetic variants that are related to poor outcome or
significant toxicity on a given drug, clinical recommendations will be provided where
specific instructions are available in the package insert. This will apply to
non-anticancer agents as well given that patients with cancer often receive multiple
agents to manage side effects and co-morbidities.

- The association between genetic variants in DMET-covered genes will be correlated with
PK/PD and clinical outcomes such as response and/or toxicity.