Enobosarm and Anastrozole in Pre-menopausal Women With High Mammographic Breast Density

Study Overview
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Brief Summary
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To evaluate the impact of a selective androgen receptor modulator combined with an aromatase inhibitor in reducing high mammographic breast density.

Detailed Description
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High mammographic breast density is a well recognized risk factor for the development of breast cancer and the masking of malignancy within the breast. Previous chemoprevention studies have revealed that only tamoxifen is efficacious in premenopausal women in the reduction of breast cancer. In order for this to occur mammographic density has to be reduced. Unfortunately the side effect profile of tamoxifen is such that not many women are taking up this therapeutic intervention. This trial is trying to establish a combination therapy to reduce mammographic breast density. This phase 1 pilot study is combining oral enobosarm, a selective androgen receptor modulator, and oral anastrozole, an aromatase inhibitor, to study the impact of this combination treatment on mammographic breast density and breast elasticity. Safety and tolerability we also analyzed.

Official Title
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A Single-Centre Pilot Trial Investigating the Efficacy and Safety of Enobosarm and Anastrozole in Pre-menopausal Women With High Mammographic Breast Density

Conditions
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Mammographic Density

Intervention / Treatment
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* Drug: enobosarm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of written informed consent Pre-menopausal levels of FSH/LH/E2 (follicle stimulating hormone, luteinizing hormone, oestrogen) according to the definition of pre-menopausal range for the laboratory involved Have a Volpara Density volumetric breast density of >15.5% (combined average both breasts) Breast pain in the previous month of equal to or greater than 40mm on a 100mm visual analogue pain scale WBC ≥ 3.0 x 109/L, granulocytes ≥ 1.5 X 109/L and platelets ≥ 100 x 109/L. AST/SGOT or ALT/SGPT ≤ 3 times ULN eGFR> 60 ml/min/1.73m2 Negative pregnancy test in women of childbearing potential (premenopausal or less than 12 months of amenorrhea post-menopause, and who have not undergone surgical sterilization), no more than 7 days before the first dose of study treatment; For women of childbearing potential who are sexually active, agreement to use a highly effective, non-hormonal form of contraception during and for at least 6 months after completion of study treatment; OR, a fertile male partner willing and able to use effective non-hormonal means of contraception (barrier method of contraception in conjunction with spermicidal jelly, or surgical sterilization) during and for at least 6 months after completion of study treatment; Exclusion Criteria: Presence of breast cancer Diabetes mellitus or glucose intolerance defined as a fasting glucose >6mmol/l Previous or concomitant other (non-breast cancer) malignancy within the previous 5 years (other than skin cancer) History of coronary artery disease Systemic hormonal contraception Risk of transmitting Human Immunodeficiency Virus or viral hepatitis via infected blood Known hypersensitivity to any component of testosterone Unable to comply with study requirements Prolonged systemic corticosteroid treatment Any investigational drugs Systemic hormone replacement therapy Pregnant or lactating women Known liver disease Current warfarin usage

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: A single armed group of premenopausal women receiving open labeled medication
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: oral enobosarm and anastrozole<br>9 mg of oral enbosarm and 1 mg of anastrozole daily | Drug: enobosarm<br>* Oral combination therapy of enobosarm and anastrozole<br>* Other names: anastrozole;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mammographic breast density | Volumetric analysis of fibroglandular density change on mammography utilizing Volpara software | 12 months | 
| Breast tissue elasticity | Evaluation of breast elasticity change by direct shear wave ultrasonic measurement | 1 month | 
| Breast tissue elasticity | Evaluation of breast elasticity change by direct shear wave ultrasonic measurement | 3 months | 
| Breast tissue elasticity | Evaluation of breast elasticity change by direct shear wave ultrasonic measurement | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Breast pain scale | Breast pain measured on a 100 mm visual analog scale | 1 month, 3 months, 12 months | 
| Serum gonadotropin levels | serum follicular stimulating hormone and luteinizing hormone levels | 1 month, 3 months, 12 months | 
| Menopausal symptoms | Menopause symptoms as recorded on a menopause symptoms scale | 3 months, 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Selective androgen receptor modulator, Aromatase inhibitor