Metabolizing Enzyme Genotype Versus Exemestane Metabolism Profiles

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01626144
Recruitment Status : Unknown
Verified June 2012 by Philip Lazarus, Milton S. Hershey Medical Center.
Recruitment status was:  Recruiting
First Posted : June 22, 2012
Last Update Posted : June 22, 2012
Information provided by (Responsible Party):
Philip Lazarus, Milton S. Hershey Medical Center

Brief Summary:
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 or disease
Breast Cancer

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
Estimated Enrollment : 200 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Metabolizing Enzyme Genotype Versus Exemestane Metabolism Profiles
Study Start Date : September 2011
Estimated Study Completion Date : January 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Exemestane
U.S. FDA Resources

Breast cancer, exemestane treatment
Breast cancer patients receiving standard of care exemestane

Primary Outcome Measures :
  1. 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

Secondary Outcome Measures :
  1. EXE toxicities [ Time Frame: 6 years ]
    Patient-reported EXE-induced toxicities will be measured.

Biospecimen Retention:   Samples With DNA
Whole blood, serum, urine

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes 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).

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01626144

Contact: Philip Lazarus, PhD 717-531-5734
Contact: Dongxiao Sun, PhD 717-531-3003 ext 289575

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

Responsible Party: Philip Lazarus, Professor of Pharmacology and Public Health Sciences, Milton S. Hershey Medical Center Identifier: NCT01626144     History of Changes
Other Study ID Numbers: 35099EP
First Posted: June 22, 2012    Key Record Dates
Last Update Posted: June 22, 2012
Last Verified: June 2012

Keywords provided by Philip Lazarus, Milton S. Hershey Medical Center:
Metabolizing enzyme genotype
Breast cancer

Additional relevant MeSH terms:
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs