Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
Please note the ANZCTR will be unattended on Monday the 7th of October for the Labour Day public holiday.
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial registered on ANZCTR
Registration number
ACTRN12614000694617
Ethics application status
Approved
Date submitted
26/06/2014
Date registered
2/07/2014
Date last updated
3/12/2020
Date data sharing statement initially provided
9/08/2019
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
Query!
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
Query!
Secondary ID [1]
284864
0
Nil known
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
BRCA-D
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Breast cancer
292266
0
Query!
Condition category
Condition code
Cancer
292621
292621
0
0
Query!
Breast
Query!
Human Genetics and Inherited Disorders
292622
292622
0
0
Query!
Other human genetics and inherited disorders
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Denosumab 120 mg monthly subcutaneous injections for 3 months
Query!
Intervention code [1]
289670
0
Prevention
Query!
Intervention code [2]
289698
0
Treatment: Drugs
Query!
Comparator / control treatment
No control
Query!
Control group
Uncontrolled
Query!
Outcomes
Primary outcome [1]
292460
0
Change in Ki67 expression assessed by immunohistochemistry in breast epithelium of BRCA1 mutation carriers.
Query!
Assessment method [1]
292460
0
Query!
Timepoint [1]
292460
0
Between baseline and after 3 months of denosumab
Query!
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.
Query!
Assessment method [1]
309011
0
Query!
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.
Query!
Secondary outcome [2]
309013
0
Change in c-KIT, ALDH1 and RANK immunostaining
Query!
Assessment method [2]
309013
0
Query!
Timepoint [2]
309013
0
Up to 42 days post-final dose of denosumab
Query!
Secondary outcome [3]
309014
0
Change in RANK and RANKL expression in epithelial and stromal cells assessed by immunohistochemistry and gene expression profile
Query!
Assessment method [3]
309014
0
Query!
Timepoint [3]
309014
0
Up to 42 days post-final dose of denosumab
Query!
Secondary outcome [4]
309015
0
Change in ER and PR expression and associated genes (e.g. BCL-2) using immunohistochemistry and gene expression profiling.
Query!
Assessment method [4]
309015
0
Query!
Timepoint [4]
309015
0
Up to 42 days post-final dose of denosumab
Query!
Secondary outcome [5]
309017
0
Change in luminal cell expression of CK5/6 using immunohistochemistry
Query!
Assessment method [5]
309017
0
Query!
Timepoint [5]
309017
0
Up to 42 days post-final dose of denosumab
Query!
Secondary outcome [6]
309018
0
Decrease in C-terminal telepeptide (CTX), calcium and free calcium levels using serum assay
Query!
Assessment method [6]
309018
0
Query!
Timepoint [6]
309018
0
Up to 42 days post-final dose of denosumab
Query!
Secondary outcome [7]
309019
0
Change in breast tissue parenchymal enhancement using BIRADS score on MRI scan
Query!
Assessment method [7]
309019
0
Query!
Timepoint [7]
309019
0
Up to 42 days post-final dose of denosumab
Query!
Eligibility
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)
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
50
Years
Query!
Query!
Sex
Females
Query!
Can healthy volunteers participate?
No
Query!
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
Query!
Study design
Purpose of the study
Prevention
Query!
Allocation to intervention
Non-randomised trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Query!
Other design features
Query!
Phase
Not Applicable
Query!
Type of endpoint/s
Efficacy
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Date of first participant enrolment
Anticipated
22/07/2014
Query!
Actual
20/11/2014
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
11/02/2020
Query!
Date of last data collection
Anticipated
Query!
Actual
30/04/2020
Query!
Sample size
Target
40
Query!
Accrual to date
Query!
Final
32
Query!
Recruitment in Australia
Recruitment state(s)
VIC
Query!
Recruitment hospital [1]
11681
0
Royal Melbourne Hospital - City campus - Parkville
Query!
Recruitment postcode(s) [1]
23727
0
3050 - Parkville
Query!
Funding & Sponsors
Funding source category [1]
289479
0
Commercial sector/Industry
Query!
Name [1]
289479
0
Amgen
Query!
Address [1]
289479
0
115 Cotham Road, Kew, Victoria 3101
Query!
Country [1]
289479
0
Australia
Query!
Primary sponsor type
Hospital
Query!
Name
Melbourne Health
Query!
Address
The Royal Melbourne Hospital, 300 Grattan Street, Parkville, VIC 3050
Query!
Country
Australia
Query!
Secondary sponsor category [1]
288164
0
None
Query!
Name [1]
288164
0
Query!
Address [1]
288164
0
Query!
Country [1]
288164
0
Query!
Ethics approval
Ethics application status
Approved
Query!
Ethics committee name [1]
291236
0
Melbourne Health HREC Committee
Query!
Ethics committee address [1]
291236
0
The Royal Melbourne Hospital 300 Grattan Street Parkville, Victoria, 3050
Query!
Ethics committee country [1]
291236
0
Australia
Query!
Date submitted for ethics approval [1]
291236
0
Query!
Approval date [1]
291236
0
17/03/2014
Query!
Ethics approval number [1]
291236
0
2014.015
Query!
Summary
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.
Query!
Trial website
https://www.transbcr.org.au
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
49446
0
Prof Geoffrey Lindeman
Query!
Address
49446
0
Department of Medical Oncology
The Royal Melbourne Hospital
300 Grattan Street
Parkville, 3050 Victoria
Query!
Country
49446
0
Australia
Query!
Phone
49446
0
+61-3-93427151
Query!
Fax
49446
0
Query!
Email
49446
0
lindeman@wehi.edu.au
Query!
Contact person for public queries
Name
49447
0
Kirsten Hogg
Query!
Address
49447
0
The Walter and Eliza Hall Institute of Medical Research
1G Royal Parade
Parkville, VIC 3052
Query!
Country
49447
0
Australia
Query!
Phone
49447
0
+61-3-9345-2805
Query!
Fax
49447
0
Query!
Email
49447
0
hogg.k@wehi.edu.au
Query!
Contact person for scientific queries
Name
49448
0
Christine Muttiah
Query!
Address
49448
0
The Walter and Eliza Hall Institute of Medical Research
1G Royal Parade
Parkville, VIC 3052
Query!
Country
49448
0
Australia
Query!
Phone
49448
0
+61-3-9345-2805
Query!
Fax
49448
0
Query!
Email
49448
0
muttiah.c@wehi.edu.au
Query!
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
Query!
No/undecided IPD sharing reason/comment
The small sample size of this 'window' study cannot ensure that collected participant data remain non-identifiable.
Query!
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
Source
Title
Year of Publication
DOI
Embase
RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers.
2016
https://dx.doi.org/10.1038/nm.4118
Embase
Bone-Targeted Therapies in Cancer-Induced Bone Disease.
2018
https://dx.doi.org/10.1007/s00223-017-0353-5
Embase
Key steps for effective breast cancer prevention.
2020
https://dx.doi.org/10.1038/s41568-020-0266-x
N.B. These documents automatically identified may not have been verified by the study sponsor.
Download to PDF