Denosumab to Prevent Breast Cancer in Women With BRCA1 Mutation

(BRCA-P Trial)

Not currently recruiting at 49 trial locations
JE
Overseen ByJudy E. Garber, MD, MPH
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 4 JurisdictionsThis treatment is already approved in other countries

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether denosumab, a treatment for managing bone loss, can help prevent breast cancer in women with a BRCA1 gene mutation. This mutation increases breast cancer risk, and researchers aim to determine if denosumab can lower that risk compared to a placebo (a substance with no active treatment). Women with a confirmed BRCA1 mutation who haven't had breast cancer or preventive breast surgery, and do not plan to, might be suitable for this trial. Participants will receive either denosumab or a placebo every six months for up to five years. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking research.

Do I have to stop taking my current medications for this trial?

The trial does not specify if you must stop all current medications, but you cannot use tamoxifen, raloxifene, aromatase inhibitors, bisphosphonates, or anti-angiogenic agents. If you've used tamoxifen, raloxifene, or aromatase inhibitors in the last 3 months or for more than 3 years total, you cannot participate. Current or prior use of aspirin or NSAIDs is allowed.

Will I have to stop taking my current medications?

The trial requires that you stop using tamoxifen, raloxifene, or aromatase inhibitors if you've used them in the last 3 months or for more than 3 years in total. You also cannot be on bisphosphonates or anti-angiogenic agents. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that denosumab is likely to be safe for humans?

Research shows that denosumab is generally safe for people. In past studies, it treated bone loss and helped prevent new bone growths in cancer patients with bone metastases. The FDA has approved denosumab for these uses, indicating a known safety record.

In studies on breast cancer risk, denosumab was associated with a 13% reduction in risk for postmenopausal women. These studies did not find major safety issues, which reassures those considering joining the trial.

Since this trial is in its later stages, substantial data already supports the safety of denosumab, indicating most people tolerate it well. Participants in other studies have not reported major side effects. However, like any medication, it can cause some side effects, so discussing any concerns with the trial team is important.1234

Why do researchers think this study treatment might be promising?

Denosumab is unique because it targets a specific pathway involved in bone resorption, which may help prevent breast cancer in women with a BRCA1 mutation. Most treatments for breast cancer focus on hormone therapy, chemotherapy, or surgery, but denosumab works by inhibiting the RANK ligand, a protein that plays a role in the development of breast cancer. Researchers are excited about denosumab because it offers a novel approach by potentially stopping cancer before it starts, particularly for those with a genetic predisposition, and it is administered as a simple injection every six months, making it a convenient option.

What evidence suggests that denosumab might be an effective treatment for preventing breast cancer in women with a BRCA1 mutation?

Research has shown that denosumab, which participants in this trial may receive, might lower the risk of breast cancer in women with a BRCA1 gene mutation. One study found that using denosumab was linked to a 13% lower chance of developing breast cancer. This medication is a monoclonal antibody, targeting specific cells in the body. Denosumab is already used to support bone health and prevent bone problems in cancer patients. These findings suggest that denosumab could effectively prevent breast cancer in those with a BRCA1 mutation.12345

Who Is on the Research Team?

JE

Judy E. Garber, MD, MPH

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

Women aged 25-55 with a BRCA1 gene mutation, no breast or ovarian cancer, and not planning preventive breast surgery can join. They must have normal recent breast exams, not be pregnant or breastfeeding, agree to use contraception, and have good physical health.

Inclusion Criteria

Written informed consent before any study-specific procedure is performed
I am fully active or restricted in physically strenuous activity but can do light work.
I have a harmful BRCA1 gene mutation.
See 5 more

Exclusion Criteria

I have low calcium levels or a history of low calcium that's relevant to my health.
Any major medical or psychiatric condition that may prevent the subject from completing the study
I am currently taking medication for bone health or to stop new blood vessels from forming.
See 12 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive denosumab or placebo subcutaneously every 6 months for up to 5 years

5 years
10 visits (in-person, every 6 months)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years
5 visits (in-person, annually)

What Are the Treatments Tested in This Trial?

Interventions

  • Denosumab
  • Quality-of-Life Assessment
Trial Overview The trial is testing if Denosumab can prevent breast cancer in women with the BRCA1 mutation compared to a placebo. It's a phase III study where participants are randomly given either Denosumab or an inactive substance while their quality of life is monitored.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Arm A (denosumab)Experimental Treatment2 Interventions
Group II: Arm B (placebo)Placebo Group2 Interventions

Denosumab is already approved in European Union, United States, Canada, Japan for the following indications:

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Approved in European Union as Prolia for:
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Approved in United States as Prolia for:
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Approved in Canada as Prolia for:
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Approved in Japan as Prolia for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials
521
Recruited
224,000+

Austrian Breast & Colorectal Cancer Study Group (ABCSG)

Collaborator

Trials
1
Recruited
300+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Published Research Related to This Trial

Denosumab, a monoclonal antibody that inhibits RANKL, shows consistent pharmacokinetics across a large population of 1,076 subjects, including both healthy individuals and cancer patients, indicating its effectiveness in preventing osteoclast activation and survival.
The study found that after administering denosumab, over 95% of patients achieved more than 97% RANKL occupancy, suggesting that dosage adjustments based on body weight, age, race, or tumor type are unnecessary for patients with bone metastases.
Population pharmacokinetic analysis of denosumab in patients with bone metastases from solid tumours.Gibiansky, L., Sutjandra, L., Doshi, S., et al.[2021]
Denosumab, a drug used to prevent bone loss, was linked to a non-healing area in the lower jaw after a tooth extraction, highlighting a potential complication associated with its use.
After stopping denosumab, the non-healing area healed successfully, suggesting that discontinuation of the drug may be necessary to allow for healing in similar cases.
Denosumab: a case of MRONJ with resolution.Lyttle, CV., Patterson, H.[2018]
Denosumab, a monoclonal antibody used to treat skeletal-related events in advanced cancer patients, shows dose-dependent pharmacokinetics, meaning its absorption and effects vary with the dose given, particularly at doses below 60 mg.
In patients with solid tumors and bone metastases, denosumab effectively reduces bone turnover markers quickly, and its pharmacokinetics and pharmacodynamics remain consistent across different tumor types and cancer treatments, indicating its broad applicability.
The pharmacokinetics and pharmacodynamics of denosumab in patients with advanced solid tumours and bone metastases: a systematic review.Sohn, W., Simiens, MA., Jaeger, K., et al.[2022]

Citations

NCT04711109 | Studying the Effect of Denosumab on ...Research has shown that denosumab may also reduce the risk of developing breast cancer in women carrying a BRCA1 germline mutation. Detailed Description.
A phase 3 study to determine the breast cancer risk ...A phase 3 study to determine the breast cancer risk reducing effect of denosumab in women carrying a germline BRCA1 mutation (BRCA-P Study).
Clinical Trial: Denosumab to Prevent Breast CancerThe trial is designed to see if denosumab every six months for five years can prevent both invasive breast cancer and DCIS in women who have a BRCA1 mutation.
Denosumab and breast cancer risk in postmenopausal ...Denosumab use was associated with a 13% decreased breast cancer risk (HR = 0.87; 95% CI 0.76–1.00). There was no relationship between increasing number of ...
Experience with denosumab (XGEVA®) for prevention of ...Patients with breast cancer and BMs who received denosumab Q4W (30, 120, or 180 mg) showed sustained uNTx/Cr suppression throughout 25 weeks of treatment, ...
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