Clinical trial NCT03264651: Enobosarm and Anastrozole in Pre-menopausal Women With High Mammographic Breast Density
Official title: A Single-Centre Pilot Trial Investigating the Efficacy and Safety of Enobosarm and Anastrozole in Pre-menopausal Women With High Mammographic Breast Density
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Mammographic Density
Keywords: Selective androgen receptor modulator
Aromatase inhibitor
Lead sponsor: Havah Therapeutics Pty Ltd
Sponsor class: INDUSTRY
Collaborators: name: GTx
First posted: 2017-08-29
Enrollment: 9
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: A single armed group of premenopausal women receiving open labeled medication
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Mammographic breast density
timeFrame: 12 months
measure: Breast tissue elasticity
timeFrame: 1 month
measure: Breast tissue elasticity
timeFrame: 3 months
measure: Breast tissue elasticity
timeFrame: 6 months
Secondary outcomes:
measure: Breast pain scale
timeFrame: 1 month, 3 months, 12 months
measure: Serum gonadotropin levels
timeFrame: 1 month, 3 months, 12 months
measure: Menopausal symptoms
timeFrame: 3 months, 12 months
Other outcomes:
Locations:
city: Toorak Gardens
country: Australia
facility: Wellend Health
state: South Australia
Study officials:
affiliation: Havah Therapeutics Pty Ltd
name: Stephen N Birrell, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: