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Trial registered on ANZCTR

Registration number
Ethics application status
Date submitted
Date registered
Date last updated
Date data sharing statement initially provided
Date results information initially provided
Type of registration
Prospectively registered

Titles & IDs
Public title
BRCA-D, a pilot study evaluating a new breast cancer prevention strategy for BRCA1 and BRCA2 mutation carriers
Scientific title
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
Secondary ID [1] 284864 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast cancer 292266 0
Condition category
Condition code
Cancer 292621 292621 0 0
Human Genetics and Inherited Disorders 292622 292622 0 0
Other human genetics and inherited disorders

Study type
Description of intervention(s) / exposure
Denosumab 120 mg monthly subcutaneous injections for 3 months
Intervention code [1] 289670 0
Intervention code [2] 289698 0
Treatment: Drugs
Comparator / control treatment
No control
Control group

Primary outcome [1] 292460 0
Change in Ki67 expression assessed by immunohistochemistry in breast epithelium of BRCA1 mutation carriers.
Timepoint [1] 292460 0
Between baseline and after 3 months of denosumab
Secondary outcome [1] 309011 0
Safety and tolerability of denosumab. Measurements to evaluate this will include vital signs, clinical laboratory tests (haematology, hepatic, renal functions and assessment of albumin-adjusted calcium). Adverse events and project-specific adverse events (osteonecrosis of the jaw, hypocalccemia, wound complications and infections during related to surgery) will also be recorded.
Timepoint [1] 309011 0
Adverse events will be assessed up to 1 month after the last administration of denosumab. Project specific adverse events will also be recorded up to 3 months after the last administration of denosumab.
Secondary outcome [2] 309013 0
Change in c-KIT, ALDH1 and RANK immunostaining
Timepoint [2] 309013 0
Up to 42 days post-final dose of denosumab
Secondary outcome [3] 309014 0
Change in RANK and RANKL expression in epithelial and stromal cells assessed by immunohistochemistry and gene expression profile
Timepoint [3] 309014 0
Up to 42 days post-final dose of denosumab
Secondary outcome [4] 309015 0
Change in ER and PR expression and associated genes (e.g. BCL-2) using immunohistochemistry and gene expression profiling.
Timepoint [4] 309015 0
Up to 42 days post-final dose of denosumab
Secondary outcome [5] 309017 0
Change in luminal cell expression of CK5/6 using immunohistochemistry
Timepoint [5] 309017 0
Up to 42 days post-final dose of denosumab
Secondary outcome [6] 309018 0
Decrease in C-terminal telepeptide (CTX), calcium and free calcium levels using serum assay
Timepoint [6] 309018 0
Up to 42 days post-final dose of denosumab
Secondary outcome [7] 309019 0
Change in breast tissue parenchymal enhancement using BIRADS score on MRI scan
Timepoint [7] 309019 0
Up to 42 days post-final dose of denosumab

Key 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)
Minimum age
18 Years
Maximum age
50 Years
Can healthy volunteers participate?
Key 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

Study design
Purpose of the study
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?

Intervention assignment
Other design features
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment status
Date of first participant enrolment
Date of last participant enrolment
Date of last data collection
Sample size
Accrual to date
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 11681 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 23727 0
3050 - Parkville

Funding & Sponsors
Funding source category [1] 289479 0
Commercial sector/Industry
Name [1] 289479 0
Country [1] 289479 0
Primary sponsor type
Melbourne Health
The Royal Melbourne Hospital, 300 Grattan Street, Parkville, VIC 3050
Secondary sponsor category [1] 288164 0
Name [1] 288164 0
Address [1] 288164 0
Country [1] 288164 0

Ethics approval
Ethics application status
Ethics committee name [1] 291236 0
Melbourne Health HREC Committee
Ethics committee address [1] 291236 0
The Royal Melbourne Hospital
300 Grattan Street
Parkville, Victoria, 3050
Ethics committee country [1] 291236 0
Date submitted for ethics approval [1] 291236 0
Approval date [1] 291236 0
Ethics approval number [1] 291236 0

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.
Trial website
Trial related presentations / publications
Public notes

Principal investigator
Name 49446 0
Prof Geoffrey Lindeman
Address 49446 0
Department of Medical Oncology
The Royal Melbourne Hospital
300 Grattan Street
Parkville, 3050 Victoria
Country 49446 0
Phone 49446 0
Fax 49446 0
Email 49446 0
Contact person for public queries
Name 49447 0
Ms Kirsten Hogg
Address 49447 0
The Walter and Eliza Hall Institute of Medical Research
1G Royal Parade
Parkville, VIC 3052
Country 49447 0
Phone 49447 0
Fax 49447 0
Email 49447 0
Contact person for scientific queries
Name 49448 0
Dr Christine Muttiah
Address 49448 0
The Walter and Eliza Hall Institute of Medical Research
1G Royal Parade
Parkville, VIC 3052
Country 49448 0
Phone 49448 0
Fax 49448 0
Email 49448 0

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
The small sample size of this 'window' study cannot ensure that collected participant data remain non-identifiable.

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseKey steps for effective breast cancer prevention.2020
EmbaseBone-Targeted Therapies in Cancer-Induced Bone Disease.2018
EmbaseRANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers.2016