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

• ClinicalTrials.gov Identifier: NCT03264651
• Recruitment Status: Completed
• First Posted: August 29, 2017
• Last Update Posted: April 18, 2018
• Sponsor: Havah Therapeutics Pty Ltd
• Collaborator: GTx
• Information provided by (Responsible Party): Havah Therapeutics Pty Ltd

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Mammographic Density	Drug: enobosarm	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: A single armed group of premenopausal women receiving open labeled medication
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: February 1, 2017
• Actual Primary Completion Date: March 21, 2018
• Actual Study Completion Date: March 21, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: oral enobosarm and anastrozole; 9 mg of oral enbosarm and 1 mg of anastrozole daily	Drug: enobosarm; Oral combination therapy of enobosarm and anastrozole; Other Name: anastrozole

Outcome Measures

Primary Outcome Measures :

1. Mammographic breast density [ Time Frame: 12 months ]
   Volumetric analysis of fibroglandular density change on mammography utilizing Volpara software
2. Breast tissue elasticity [ Time Frame: 1 month ]
   Evaluation of breast elasticity change by direct shear wave ultrasonic measurement
3. Breast tissue elasticity [ Time Frame: 3 months ]
   Evaluation of breast elasticity change by direct shear wave ultrasonic measurement
4. Breast tissue elasticity [ Time Frame: 6 months ]
   Evaluation of breast elasticity change by direct shear wave ultrasonic measurement

Secondary Outcome Measures :

1. Breast pain scale [ Time Frame: 1 month, 3 months, 12 months ]
   Breast pain measured on a 100 mm visual analog scale
2. Serum gonadotropin levels [ Time Frame: 1 month, 3 months, 12 months ]
   serum follicular stimulating hormone and luteinizing hormone levels
3. Menopausal symptoms [ Time Frame: 3 months, 12 months ]
   Menopause symptoms as recorded on a menopause symptoms scale

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Australia, South Australia

Wellend Health

Toorak Gardens, South Australia, Australia, 5065

Sponsors and Collaborators

Havah Therapeutics Pty Ltd

GTx

Investigators

• Principal Investigator: Stephen N Birrell, MD PhD; Havah Therapeutics Pty Ltd

More Information

• Responsible Party: Havah Therapeutics Pty Ltd
• ClinicalTrials.gov Identifier: NCT03264651
• Other Study ID Numbers: CH02ST1
• First Posted: August 29, 2017
• Last Update Posted: April 18, 2018
• Last Verified: February 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Havah Therapeutics Pty Ltd:

Selective androgen receptor modulator; Aromatase inhibitor

Additional relevant MeSH terms:

Anastrozole; Antineoplastic Agents, Hormonal; 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