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

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

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

Study Overview

• Status: Completed
• Conditions: Mammographic Density
• Intervention / Treatment: Drug: enobosarm

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 Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Toorak Gardens, South Australia, Australia, 5065
      • Wellend Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: anastrozole

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Havah Therapeutics Pty Ltd
• Collaborators: GTx
• Investigators: Principal Investigator: Stephen N Birrell, MD PhD, Havah Therapeutics Pty Ltd

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2017
• Primary Completion (Actual): March 21, 2018
• Study Completion (Actual): March 21, 2018

Study Registration Dates

• First Submitted: August 14, 2017
• First Submitted That Met QC Criteria: August 28, 2017
• First Posted (Actual): August 29, 2017

Study Record Updates

• Last Update Posted (Actual): April 18, 2018
• Last Update Submitted That Met QC Criteria: April 17, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Aromatase inhibitor; Selective androgen receptor modulator
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Anastrozole
• Other Study ID Numbers: CH02ST1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No