Prospective Screening for Patient-Specific Genotypes and Phenotypes That Influence Drug Dosing and Trial Selection in Cancer Patients

Background: Genetic sequence of drug-metabolizing enzymes, transporters/receptors, transcription factors, drug targets, and patient baseline characteristics often affect an individual s response to drug therapy. Expression of such genes is also influenced by the epigenome and regulation by a variety of other factors: RNA expression, protein expression, disease state, comorbidities, concomitant therapies, etc. Therefore, inter-patient variability in drug pharmacokinetics and outcome is often a function of these factors. 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 variability in pharmacokinetics, pharmacodynamics, clinical outcome, and toxicity are often noted. Many of these differences are potentially clinically actionable and depend on the aforementioned markers. Objectives: To screen patients for genomic markers, epigenomic markers, RNA markers, protein markers, and/or baseline characteristics that are used inform either enrollment in therapeutic clinical trials or dose selection of investigational anticancer agents. Eligibility: All individuals seeking enrollment on National Cancer Institute clinical trials that include a priori assessment of a patients genome, epigenome, proteome, or baseline characteristics as eligibility criteria for enrollment or dose selection. Design: This study will be used as a screening protocol to enroll patients for a priori screening that is necessary for inclusion in IRB-approved clinical trials taking place at the NCI. As the rationale for ascertaining the status of a marker prior to study inclusion will be presented in the associated clinical trial, the present study will be amended on a case-by-case basis. The accrual ceiling for this study is 900 patients.