BRCA-P: A Cancer Prevention study to determine if Denosumab can prevent Breast Cancer Development in Women carrying a BRCA1 Germline Mutation

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Verein Zur Praevention Und Therapie Boesartiger Erkrankungen Austrian Breast And Colorectal Cancer Study Group, Institut Catala D'oncologia, ANZ Breast Cancer Trials Group Limited, University Of Manchester, Alliance Foundation Trials LLC, Shaare Zedek Medical Center

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

3 Jul 2019 → ongoing

Decision date (initial)

2024-08-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Amgen Ltd.

External identifiers

EU CT number

2024-513734-38-00

EudraCT number

2017-002505-35

ClinicalTrials.gov

NCT04711109

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Efficacy, Prophylaxis, Therapy, Pharmacogenetic, Safety

To evaluate the reduction in the risk of any breast cancer (invasive or DCIS) in women with germline BRCA1 mutation who are treated with denosumab compared to placebo

Secondary objectives 6

1. (1) To determine the reduction in risk of invasive breast cancer
2. (2) To determine the reduction in risk of invasive triple negative breast cancer (TNBC)
3. (3) To determine the reduction in risk of ovarian, fallopian tube cancers (in women who have not undergone PBSO) and primary peritoneal cancers in women with germline BRCA1 mutation who are treated with denosumab compared to placebo
4. (4) To determine the reduction in the risk of other (i.e. non-breast and non-ovarian) malignancies, including those known to be associated with BRCA1 germline mutations in women with germline BRCA1 mutation who are treated with denosumab compared to placebo
5. (5) To compare rates of breast biopsies and rate of benign breast lesions in women with germline BRCA1 mutation who are treated with denosumab compared to placebo
6. (6) To determine the reduction in the risk of clinical fractures in pre- and postmenopausal women with germline BRCA1 mutation who are treated with denosumab compared to placebo

Conditions and MedDRA coding

Prevention of breast cancer in women with a BRCA1 germline mutation

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Women with a confirmed deleterious or likely deleterious BRCA 1 germline mutation (Variant class 4 or 5)
2. Age ≥ 25 years and ≤ 55 years at randomization
3. No evidence of breast cancer by MRI or MG and clinical breast examination within the last 6 months prior to randomization
4. No clinical evidence of ovarian cancer at randomization
5. Negative pregnancy test at randomization for women of childbearing potential
6. No preventive breast surgery planned at time of randomization
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
8. Written informed consent before any study-specific procedure is performed

Exclusion criteria 17

1. Prior bilateral mastectomy
2. History of ovarian cancer (including fallopian tube and primary peritoneal cancer)
3. History of breast cancer
4. History of invasive cancer except for basal cell or squamous cell skin cancer. History of the following are also allowed: carcinoma in situ of the cervix, stage 1 papillary or follicular thyroid cancer, atypical hyperplasia or LCIS (Lobular Carcinoma In Situ)
5. Pregnant or lactating women (within the last 2 months prior to randomization)
6. Unwillingness to use highly effective contraception method during and within at least 5 months after cessation of denosumab/placebo therapy in women of childbearing potential
7. Clinically relevant hypocalcaemia (history and current condition), or serum calcium <2.0 mmol/L (<8.0 mg/dL) or corrected calcium (<2.1 mmol/L) Hypocalcemia defined by calcium below the normal range (a single value below the normal range does not necessarily constitute hypocalcemia, but should be 'corrected' before dosing the participant). Monitoring of calcium level in regular intervals (usually prior to IP administration) is highly recommended
8. Tamoxifen, raloxifene or aromatase inhibitor use during the last 3 months prior to randomization or for a duration of more than 3 years in total (current and prior HRT is permitted)
9. Any prior use of denosumab
10. Participant has a known prior history or current evidence of osteonecrosis or osteomyelitis of the jaw, or an active dental/jaw condition which requires oral surgery including tooth extraction ≤ 3 months prior enrollment
11. Concurrent treatment with a bisphosphonate or an anti-angiogenic agent
12. Concurrent therapy with other Investigational Products
13. Any major medical or psychiatric condition that may prevent the participant from completing the study
14. Known active infection with Hepatitis B virus or Hepatitis C virus
15. Known infection with human immunodeficiency virus (HIV)
16. Hypersensitivity to the active substance or to any of the excipients
17. Known rare hereditary problems of fructose intolerance

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to the occurrence of any breast cancer (invasive or DCIS)

Secondary endpoints 6

1. Time to invasive breast cancer
2. Time to invasive triple negative breast cancer
3. Time to ovarian, fallopian tube or primary peritoneal cancer (in women who have not undergone PBSO)
4. Time to other (non breast or ovarian cancer) malignancies, including those known to be associated with BRCA1 mutations
5. Time to clinical fractures in pre- and postmenopausal women
6. Frequency of breast biopsies and frequency of benign breast lesions

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Verein Zur Praevention Und Therapie Boesartiger Erkrankungen Austrian Breast And Colorectal Cancer Study Group

Sponsor organisation

Verein Zur Praevention Und Therapie Boesartiger Erkrankungen Austrian Breast And Colorectal Cancer Study Group

Address

Nussdorfer Platz 8/8/12

City

Vienna

Postcode

1190

Country

Austria

Scientific contact point

Organisation

Verein Zur Praevention Und Therapie Boesartiger Erkrankungen Austrian Breast And Colorectal Cancer Study Group

Contact name

Trial Office

Public contact point

Organisation

Verein Zur Praevention Und Therapie Boesartiger Erkrankungen Austrian Breast And Colorectal Cancer Study Group

Contact name

Trial Office

Institut Catala D'oncologia

Sponsor organisation

Institut Catala D'oncologia

Address

Avinguda De La Gran Via De L'hospitalet 199-203

City

L'hospitalet De Llobregat

Postcode

08908

Country

Spain

Scientific contact point

Organisation

Institut Catala D'oncologia

Contact name

VHIO CRS Unit

Public contact point

Organisation

Institut Catala D'oncologia

Contact name

VHIO CRS Unit

ANZ Breast Cancer Trials Group Limited

Sponsor organisation

ANZ Breast Cancer Trials Group Limited

Address

Level 4 175 Scott Street

City

Newcastle

Postcode

2300

Country

Australia

University Of Manchester

Sponsor organisation

University Of Manchester

Address

Oxford Road

City

Manchester

Postcode

M13 9WL

Country

United Kingdom

Alliance Foundation Trials LLC

Sponsor organisation

Alliance Foundation Trials LLC

Address

221 Longwood Avenue Suite 108

City

Boston

Postcode

02115-5804

Country

United States

Shaare Zedek Medical Center

Sponsor organisation

Shaare Zedek Medical Center

Address

12 Shmu'el Bait

City

Jerusalem

Postcode

9372212

Country

Israel

Sponsor responsibilities

Article 77 compliance

Verein Zur Praevention Und Therapie Boesartiger Erkrankungen Austrian Breast And Colorectal Cancer Study Group

Contact point sponsor

Verein Zur Praevention Und Therapie Boesartiger Erkrankungen Austrian Breast And Colorectal Cancer Study Group

Article 77 implementation

Verein Zur Praevention Und Therapie Boesartiger Erkrankungen Austrian Breast And Colorectal Cancer Study Group

Locations

3 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications