Metabolizing Enzyme Genotype Versus Exemestane Metabolism Profiles

May 23, 2018 updated by: Milton S. Hershey Medical Center
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 Overview

Status

Completed

Conditions

Detailed Description

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.

Study Type

Observational

Enrollment (Actual)

170

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Penn State Milton S. Hershey Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

Post-menopausal breast cancer patients in the breast oncology clinic at the Penn State Hershey Cancer Institute (PSHCI).

Description

Inclusion Criteria:

  • Breast cancer patients who have ER+ tumors and are taking 25 mg EXE daily (orally)
  • Post-menopausal women or chemically post-menopausal women (who won't become pregnant since they are taking zoladex), or women who are post-menopausal as a result of ovary removal
  • Patients may be at any point in their hormonal treatment, but must have completed any planned surgery, radiation and chemotherapy.

Exclusion Criteria:

  • Concurrent use of corticosteroids, megestrol, or phenobarbitol (inhaled and internasal steroids are permitted)
  • History of allergy to exemestane

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Breast cancer, exemestane treatment
Breast cancer patients receiving standard of care exemestane

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Metabolizing enzyme genotype vs EXE metabolism profiles
Time Frame: 6 years
Functional genotypes will be determined for EXE-metabolizing enzymes and will be correlated with blood/urinary EXE metabolism profiles
6 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
EXE toxicities
Time Frame: 6 years
Patient-reported EXE-induced toxicities will be measured.
6 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Philip Lazarus, Ph.D., Penn State College of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2011

Primary Completion (Actual)

April 18, 2017

Study Completion (Actual)

May 1, 2018

Study Registration Dates

First Submitted

June 20, 2012

First Submitted That Met QC Criteria

June 21, 2012

First Posted (Estimate)

June 22, 2012

Study Record Updates

Last Update Posted (Actual)

May 25, 2018

Last Update Submitted That Met QC Criteria

May 23, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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