Metabolizing Enzyme Genotype Versus Exemestane Metabolism Profiles
It is the investigators hypothesis that exemestane (EXE) metabolism is an important source of the inter-individual variation in EXE metabolic profiles and that polymorphisms in EXE-metabolizing enzymes may potentially play a role in affecting EXE therapeutic efficacy and toxicity. The goals of this clinical study are to (1) establish EXE metabolism profile kinetics, and (2) determine whether correlations exist in vivo between metabolizing enzyme genotype and urinary EXE metabolite profiles in women being treated with EXE. Together, these studies will allow us to fully characterize functionally-relevant polymorphisms in the EXE-metabolizing enzyme pathway that are potentially important in EXE clinical efficacy.
|Study Design:||Observational Model: Case-Only
Time Perspective: Prospective
|Official Title:||Metabolizing Enzyme Genotype Versus Exemestane Metabolism Profiles|
- Metabolizing enzyme genotype vs EXE metabolism profiles [ Time Frame: 6 years ] [ Designated as safety issue: No ]Functional genotypes will be determined for EXE-metabolizing enzymes and will be correlated with blood/urinary EXE metabolism profiles
- EXE toxicities [ Time Frame: 6 years ] [ Designated as safety issue: No ]Patient-reported EXE-induced toxicities will be measured.
Biospecimen Retention: Samples With DNA
Whole blood, serum, urine
|Study Start Date:||September 2011|
|Estimated Study Completion Date:||January 2017|
Breast cancer, exemestane treatment
Breast cancer patients receiving standard of care exemestane
Aromatase inhibitors (AIs) are widely used as adjuvant treatment for estrogen-receptor positive breast cancer in post-menopausal women. AIs have been demonstrated to have equal to or greater efficacy and less toxicity than tamoxifen (TAM), the drug of choice for many years. Exemestane (EXE) is a 3rd-generation AI that has demonstrated efficacy in the treatment of breast cancer patients, and as with TAM and other AIs, there has been considerable inter-individual variability in overall response to EXE and in the occurrence of toxicities, but the causes of this variability have not been elucidated. Differences in drug metabolism can be a source of variability between patients. Genetic variations occur in several of the enzymes involved in phase I and II metabolic reactions and many of these can lead to alterations in enzyme activity which in turn can alter therapeutic response to drugs. EXE is extensively metabolized as unchanged EXE and is found at less than 1% in urine and 10% in plasma. EXE pharmacokinetics will be established in a series of 20 subjects taking EXE. EXE metabolites will then be measured at an optimal time post-EXE dose in the urine of 200 breast cancer patients being treated with EXE to establish whether metabolizing enzyme genotype-EXE metabolism phenotype correlations exist in vivo.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01626144
|Contact: Philip Lazarus, PhDfirstname.lastname@example.org|
|Contact: Dongxiao Sun, PhD||717-531-3003 ext email@example.com|
|United States, Pennsylvania|
|Penn State Milton S. Hershey Medical Center||Recruiting|
|Hershey, Pennsylvania, United States, 17033|
|Principal Investigator: Philip Lazarus, Ph.D.|
|Sub-Investigator: Leah Cream, MD|
|Sub-Investigator: Donxiao Sun, PhD|
|Principal Investigator:||Philip Lazarus, Ph.D.||Penn State College of Medicine|