ANZCTR - Registration

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.

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

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

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

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]

Nil known

Universal Trial Number (UTN)

Trial acronym

BRCA-D

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Breast cancer

Condition category

Condition code

Cancer

Breast

Human Genetics and Inherited Disorders

Other human genetics and inherited disorders

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Denosumab 120 mg monthly subcutaneous injections for 3 months

Intervention code [1]

Prevention

Intervention code [2]

Treatment: Drugs

Comparator / control treatment

No control

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Change in Ki67 expression assessed by immunohistochemistry in breast epithelium of BRCA1 mutation carriers.

Timepoint [1]

Between baseline and after 3 months of denosumab

Secondary outcome [1]

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]

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]

Change in c-KIT, ALDH1 and RANK immunostaining

Timepoint [2]

Up to 42 days post-final dose of denosumab

Secondary outcome [3]

Change in RANK and RANKL expression in epithelial and stromal cells assessed by immunohistochemistry and gene expression profile

Timepoint [3]

Up to 42 days post-final dose of denosumab

Secondary outcome [4]

Change in ER and PR expression and associated genes (e.g. BCL-2) using immunohistochemistry and gene expression profiling.

Timepoint [4]

Up to 42 days post-final dose of denosumab

Secondary outcome [5]

Change in luminal cell expression of CK5/6 using immunohistochemistry

Timepoint [5]

Up to 42 days post-final dose of denosumab

Secondary outcome [6]

Decrease in C-terminal telepeptide (CTX), calcium and free calcium levels using serum assay

Timepoint [6]

Up to 42 days post-final dose of denosumab

Secondary outcome [7]

Change in breast tissue parenchymal enhancement using BIRADS score on MRI scan

Timepoint [7]

Up to 42 days post-final dose of denosumab

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)

Minimum age

18 Years

Maximum age

50 Years

Sex

Females

Can healthy volunteers participate?

No

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

Prevention

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

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

22/07/2014

Actual

20/11/2014

Date of last participant enrolment

Anticipated

Actual

11/02/2020

Date of last data collection

Anticipated

Actual

30/04/2020

Sample size

Target

40

Accrual to date

Final

32

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Royal Melbourne Hospital - City campus - Parkville

Recruitment postcode(s) [1]

3050 - Parkville

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Amgen

Address [1]

115 Cotham Road, Kew, Victoria 3101

Country [1]

Australia

Primary sponsor type

Hospital

Name

Melbourne Health

Address

The Royal Melbourne Hospital, 300 Grattan Street, Parkville, VIC 3050

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Melbourne Health HREC Committee

Ethics committee address [1]

The Royal Melbourne Hospital
300 Grattan Street
Parkville, Victoria, 3050

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

17/03/2014

Ethics approval number [1]

2014.015

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.

Trial website

https://www.transbcr.org.au

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Geoffrey Lindeman

Address

Department of Medical Oncology
The Royal Melbourne Hospital
300 Grattan Street
Parkville, 3050 Victoria

Country

Australia

Phone

+61-3-93427151

Fax

Email

lindeman@wehi.edu.au

Contact person for public queries

Name

Kirsten Hogg

Address

The Walter and Eliza Hall Institute of Medical Research
1G Royal Parade
Parkville, VIC 3052

Country

Australia

Phone

+61-3-9345-2805

Fax

Email

hogg.k@wehi.edu.au

Contact person for scientific queries

Name

Christine Muttiah

Address

The Walter and Eliza Hall Institute of Medical Research
1G Royal Parade
Parkville, VIC 3052

Country

Australia

Phone

+61-3-9345-2805

Fax

Email

muttiah.c@wehi.edu.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No

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

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.