BRCA-D, a pilot study evaluating a new breast cancer prevention strategy for BRCA1 and BRCA2 mutation carriers

A pre-operative window study evaluating the biological effects of the RANK-Ligand (RANKL) inhibitor Denosumab on normal breast tissue from BRCA1 and BRCA2 mutation carriers

Status

Completed

Phases

Unknown

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12614000694617

Acronym

BRCA-D

Enrollment

Registered

2014-07-02

Start date

2014-11-20

Completion date

2020-02-11

Last updated

2020-12-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

This study will determine the effects of Denosumab on normal breast tissue in women with BRCA1 and BRCA2 mutations. Who is it for? You may be eligible to join this study if you are a pre-menopausal woman aged between 18 years to 50 years and have documented BRCA1 or BRCA2 mutation considering prophylactic mastectomy, OR willing to undergo two breast biopsies on separate occasions. Study details This is a proof-of-concept pilot study to determine if short-term treatment with Denosumab is a feasible chemoprevention option against breast cancer for BRCA1 and BRCA2 mutation carriers. All women participating in the study will receive 3 doses of 120mg per dose of Denosumab subcutaneously (injected into the skin) monthly for three months. Women will then proceed to their surgery as planned, or have their second breast biopsy. Participants will be followed up for up to 3 months after the last treatment dose. The change in the number of doses of Denosumab (from 4 to 3) was implemented in September 2015, after 6 patients had been enrolled.

Interventions

Denosumab 120 mg monthly subcutaneous injections for 3 months

Study design

Allocation

Non-randomised trial

Primary purpose

Prevention

Eligibility

Sex/Gender

All

Age

18 Years to 50 Years

Healthy volunteers

Inclusion criteria

1. Documented BRCA1 or BRCA2 mutation carriers 2. ECOG 0-1 3. Premenopausal status 4. Serum calcium or albumin adjusted calcium >2.0mmol/L and <2.9 mmol/L 5. Must agree to take Calcium and Vitamin D supplementation 6. Subjects with reproductive potential must be willing to use acceptable methods of effective contraception (with the exception of hormonal contraception)

Exclusion criteria

1. BRCA1 or BRCA2 variants that are considered to be non detrimental or where pathogenicity is unknown 2. Active breast cancer 3. Previous irradiation of the breast to be studied 4. Previous bilateral oophorectomy 5. Pregnancy and lactation 6. Hormonal contraception (Mirena IUD is allowed) with a washout period of at least 3 months prior to first dose of study drug 7. Endocrine therapy use in the last 6 months for the purpose of risk reduction 7. History of non-breast malignancies within the last 5 years, except cervical carcinoma in-situ, melanoma in-situ, skin BCC or SCC or Stage 1 thyroid cancer 8. Prior history or current evidence of osteonecrosis of the jaw 9. Active dental/jaw condition requiring oral surgery including tooth extraction 10. Previous treatment with denosumab

Outcome results