Metabolizing Enzyme Genotype Versus Exemestane Metabolism Profiles

Breast Cancer Clinical Trial

Official title:

Metabolizing Enzyme Genotype Versus Exemestane Metabolism Profiles

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01626144
• Other study ID #: 35099EP
• Status: Completed
• Start date: September 2011
• Est. completion date: May 1, 2018

Study information

• Verified date: May 2018
• Source: Milton S. Hershey Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 170
• Est. completion date: May 1, 2018
• Est. primary completion date: April 18, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer

Locations

Country	Name	City	State
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Milton S. Hershey Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Metabolizing enzyme genotype vs EXE metabolism profiles	Functional genotypes will be determined for EXE-metabolizing enzymes and will be correlated with blood/urinary EXE metabolism profiles	6 years
Secondary	EXE toxicities	Patient-reported EXE-induced toxicities will be measured.	6 years