Metabolizing Enzyme Genotype Versus Exemestane Metabolism Profiles

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2012 by Milton S. Hershey Medical Center
Sponsor:
Information provided by (Responsible Party):
Philip Lazarus, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier:
NCT01626144
First received: June 20, 2012
Last updated: June 21, 2012
Last verified: June 2012
  Purpose

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.


Condition
Breast Cancer

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Metabolizing Enzyme Genotype Versus Exemestane Metabolism Profiles

Resource links provided by NLM:


Further study details as provided by Milton S. Hershey Medical Center:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 200
Study Start Date: September 2011
Estimated Study Completion Date: January 2017
Groups/Cohorts
Breast cancer, exemestane treatment
Breast cancer patients receiving standard of care exemestane

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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).

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01626144

Contacts
Contact: Philip Lazarus, PhD 717-531-5734 plazarus@psu.edu
Contact: Dongxiao Sun, PhD 717-531-3003 ext 289575 dsun@hmc.psu.edu

Locations
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         
Sponsors and Collaborators
Milton S. Hershey Medical Center
Investigators
Principal Investigator: Philip Lazarus, Ph.D. Penn State College of Medicine
  More Information

No publications provided

Responsible Party: Philip Lazarus, Professor of Pharmacology and Public Health Sciences, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier: NCT01626144     History of Changes
Other Study ID Numbers: 35099EP
Study First Received: June 20, 2012
Last Updated: June 21, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Milton S. Hershey Medical Center:
Exemestane
Metabolism
Metabolizing enzyme genotype
Breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Exemestane
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014