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.