None listed
Conditions
Brief summary
This study is testing whether a new hormone-based therapy called HAV-088 (a combination of testosterone and an aromatase inhibitor) can help reduce breast cancer risk in premenopausal women. Who is it for? You may be eligible for this study if you are aged between 25 and 50, you are not currently going through menopause or peri-menopause, and you are at-risk of developing breast cancer - defined as meeting one of the following: history of abnormal cell growth in the breasts, known BRCA1/2 or other high-risk gene mutation, or extremely dense breasts. Study details Participants who choose to enrol in this study will be randomly allocated by chance (similar to flipping a coin) to one of two treatment groups. Participants allocated to the first group will be asked to take an oral dose of tamoxifen each day for 1 year. Participants allocated to the second group will be asked to have a slow-release HAV-088 pellet injected into soft tissue (with local anaesthetic) near their hips once every 3 months for 1 year. All participants will be asked to attend two MRI scans and will also be asked to provide blood samples and fill out questionnaires about their symptoms and quality of life throughout the study. It is hoped this research will determine that HAV-088 is a safe treatment for women at high-risk of developing breast cancer, while preserving ovarian function and causing fewer side effects than tamoxifen. If this small study is positive, a larger study enrolling a greater number of women at high-risk of developing breast cancer may be undertaken.
Interventions
Intervention – HAV-088 (Arm B)
Brief Name: HAV-088 (Testosterone + Aromatase Inhibitor)
Type of Intervention: Investigational hormonal therapy for breast cancer prevention.
Intervention Description: HAV-088 is a subcutaneous implant containing two active pharmaceutical ingredients: Testosterone (INN): 100 mg and Anastrozole (INN): 4 mg. The formulation is a compressed sterile pellet, 5 mm diameter, composed of:
Testosterone USP: 100 mg (93.5%)
Anastrozole USP: 4 mg (3.7%)
Stearic acid NF: 3 mg
Intervention – HAV-088 (Arm B) Brief Name: HAV-088 (Testosterone + Aromatase Inhibitor) Type of Intervention: Investigational hormonal therapy for breast cancer prevention. Intervention Description: HAV-088 is a subcutaneous implant containing two active pharmaceutical ingredients: Testosterone (INN): 100 mg and Anastrozole (INN): 4 mg. The formulation is a compressed sterile pellet, 5 mm diameter, composed of: Testosterone USP: 100 mg (93.5%) Anastrozole USP: 4 mg (3.7%) Stearic acid NF: 3 mg (2.8%) – lubricant The pellets are compounded by Green Dispensary (St Peters, SA), compliant with PRASA and 503A/B standards and supplied in amber glass vials. Storage is at room temperature (15–30°C), protected from light; testosterone is a Schedule III controlled substance requiring secure storage Dose Administered: 1 Pellet administered at Month 0, Month 3, Month 6, and Month 9 Duration of Administration: 12 months total (4 pellet insertions over the course of the study) Mode of Administration: Subcutaneous implant (pellet inserted under local anesthesia into subdermal fatty tissue, e.g., hip or abdominal area) Delivery Method: Administered in-person by qualified clinical staff at Wellend Health during scheduled study visits. Location of Delivery: Wellend Health, Nyroca House, North Adelaide, SA. Tailoring: The intervention is not tailored or titrated; all participants in Arm B receive the same fixed dose and schedule. Adherence/Fidelity Monitoring: Compliance is ensured by direct administration by clinical staff. Each pellet insertion is documented in the participant’s source records and study-specific accountability logs. Hormone levels (FSH, LH, testosterone, estradiol) are monitored at each visit to confirm ovarian function is preserved and to assess pharmacodynamic effects.
Sponsors
Wellend Health
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
25 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
All criteria must be met to participate 1. Premenopausal women age 25 to 50 years (inclusive). 2. High risk for breast cancer, defined as meeting one of the following: (a) equal to of higher than 20 percent lifetime risk by IBIS/Tyrer-Cuzick model; (b) history of atypical hyperplasia or LCIS; (c) known pathogenic BRCA1/2 or other high-risk gene mutation; or (d) extremely dense breasts (BI-RADS D or volumetric density equal to 15 percent). 3. High breast density on mammogram (BI-RADS category D or equivalent quantitative measure) and marked background parenchymal enhancement on a screening breast MRI (qualitative MRI report of “marked BPE”). 4. No prior history of invasive breast cancer or ductal carcinoma in situ (DCIS). 5. Willing to undergo baseline and follow-up MRI, and to use effective non-hormonal contraception during the study (given the teratogenic risks of the study drugs). 6. Able to understand and willing to sign the informed consent form.
Exclusion criteria
Subjects will be excluded if any of the following apply 1. Medical contraindications to tamoxifen: history of venous thromboembolism, stroke, or endometrial or any other cancer; known clotting disorder; uncontrolled uterine bleeding or uterine pathology precluding SERM use. 2. Contraindications to HAV-088 therapy: active liver disease or elevated liver enzymes (as testosterone and AIs are metabolized hepatically), history of severe adverse reaction to testosterone or aromatase inhibitors, or conditions aggravated by androgens (such as severe acne or polycythemia). 3. Current or recent (within 3 months) use of any hormone therapy for prevention (e.g. SERMs, AIs) or oral contraceptives. (A washout period of 3 months is required if previously on such agents.) 4. Pregnant or breastfeeding or planning to become pregnant in the next year. (A negative pregnancy test is required at screening; pregnant women are excluded due to risk to the fetus.) 5. Ovarian suppression or oophorectomy (since the study focuses on women with intact ovarian function). 6. Any serious uncontrolled comorbid condition that would interfere with participation or safety (e.g. uncontrolled diabetes or heart disease, severe psychiatric conditions). 7. Participation in another interventional trial for breast cancer prevention at the same time. 8. Any investigational drugs or participation in any other clinical study for 6 weeks or 5 half-life period (in case of an experimental drug, whichever is longer) prior to screening. 9. Any reason that the Investigator’s or the sponsor’s opinion may preclude the participant from inclusion onto study.
Outcome results
None listed