A trial looking at denosumab and the risk of breast cancer in women with changes to the BRCA1 gene (BRCA-P)

Cancer type:

Breast cancer

Status:

Open

Phase:

Phase 3

This trial is for women who have changes to the BRCA1 Open a glossary item gene but do not have cancer. It is looking at a new way to try and prevent breast cancer.

More about this trial

People who have a very strong family history of certain cancers may have a faulty gene in their family that increases the risk of cancer.

Everyone has BRCA1 and BRCA2 genes. BRCA stands for BReast CAncer gene. They are important genes that stop the cells in our body from growing and dividing out of control. Doctors call these tumour suppressor genes.

A fault (or mutation) in the BRCA1 or BRCA2 gene means that the cells can grow out of control. This can lead to cancer developing.

Faulty BRCA1 and BRCA2 genes are rare. Only around 1 in every 400 people have a faulty BRCA1 or BRCA2 gene.

Both men and women can have a faulty BRCA1 or BRCA2 gene. People who inherit faulty versions of these genes have an increased risk of developing different types of cancers. These include:

There are treatments that can reduce the risk of developing breast or ovarian cancer in women with a change in the BRCA1 gene. These are:

surgery to remove the breasts (mastectomy)
surgery to remove the ovaries
hormone treatment

Researchers would like to reduce the risk of cancer developing in women with this increased cancer risk.

Denosumab is a type of targeted therapy called a monoclonal antibody Open a glossary item .

In healthy bones, specialised cells constantly break down and replace old tissue. These specialised bone cells are:

osteoclasts, which break down old bone
osteoblasts, which build new bone

Denosumab works by targeting a protein called RANKL which controls the activity of osteoclasts. This stops bone cells being broken down and strengthens the bone. Doctors use it for managing bone health in people with and without cancer. They would now like to find out if denosumab could help to prevent cancer.

The aims of the trial are to find out:

if denosumab can help prevent breast cancer, and other cancers, in women with changes in the BRCA1 gene
if denosumab affects the development of breast lumps that are not cancer (benign)
more about the effect of denosumab on bone health
more about the safety of denosumab
if there are substances that doctors can measure in the body (biomarkers) which can help them to diagnose breast cancer early
more about hormones and breast cancer
more about quality of life

Who can enter

The following bullet points are a summary of the entry conditions for this trial. Talk to your doctor or the trial team if you are unsure about any of these. They will be able to advise you.

Who can take part

You may be able to join this trial if all of the following apply:

you are female and have a change in the BRCA1 gene (this is also called a BRCA1 mutation)
you do not have breast cancer or ovarian cancer at the time of randomisation
you have talked about surgery to try and prevent breast cancer with your team, but you are not planning surgery at the time of randomisation
your doctor, or you, do not think other drug options would be right for you at the moment, these drugs include tamoxifen, raloxifene or aromatase inhibitors
you can look after yourself but might not be able to do heavy physical work (performance status 0 or 1)
have satisfactory blood test results
you are willing to use reliable contraception during the trial and for 5 months after finishing the study treatment if there is a chance you could become pregnant. Your trial team can talk about suitable contraception for you and your partner if needed.
you are at least 25 years old, and you are not yet 56 years old, at the time of randomisation

Who can’t take part

Cancer related
You cannot join this trial if any of these apply. You:

have had ovarian cancer before, including primary peritoneal cancer and fallopian tube cancer
have had breast cancer before
have had cancer in the past apart from basal cell skin cancer or squamous cell skin cancer . You might still be able to take part if you have had very early cervical cancer (in situ), early stage (stage 1) papillary or follicular thyroid cancer or certain breast conditions that are not cancer (atypical hyperplasia or lobular carcinoma in situ )
have had an operation to remove both breasts (mastectomy)
have had tamoxifen, raloxifene or aromatase inhibitor treatment during the 3 months before randomisation. Or you have taken these drugs for more than 3 years in total.
are taking any drugs that block cancer blood vessel growth (anti angiogenic drugs). Your doctor can explain more.

Medical conditions
You cannot join this trial if any of these apply. You:

have ever had osteonecrosis of the jaw or an infection of the jaw bone (osteomyelitis)
have had any jaw or dental problems which needed surgery or a tooth out within 3 months of joining the trial
have long term (chronic) liver problems . Your doctor can explain more about this.
have active hepatitis B, active hepatitis C or HIV

Other
You cannot join this trial if any of these apply. You:

have taken denosumab before
are taking bisphosphonates at the moment
are pregnant or are breastfeeding. Or you have been pregnant or breastfeeding in the 2 months before randomisation.
are allergic or sensitive to denosumab or any of its ingredients
are not able to break down fructose (fructose intolerance). Your doctor can explain more
are taking an experimental drug at the moment
have any other medical condition or mental health problem that could affect you taking part

Trial design

This is an international phase 3 trial. The researchers need around 2,918 people to take part including 80 from the UK.

It is a randomised double blind trial. You are put into a group by a computer. Neither you nor your doctor will be able to decide which group you are in. Nor will you or your doctor know which treatment you have. During the trial your doctor will be able to find out what treatment you are having, if necessary. There are 2 treatment groups.

Group 1 – you have denosumab.
Group 2 – you have a dummy drug (placebo).

BRCA-P trial randomisation diagram

You have denosumab or the dummy drug as an injection under the skin. You have your injection every 6 months for 5 years.

Follow up
After finishing the five years of treatment, your trial doctor will continue to keep in contact for a further 5 years. This is called follow up. You will be in the trial for up to 10 years.

Blood samples for research
The team ask to take some extra blood samples. Where possible, you have these at the same time as any routine blood tests.

They plan to use the samples to help research into preventing, diagnosing and treating cancer in the future,

You don’t have to give these samples if you don’t want to. You can still take part in the trial.

Quality of life study
The trial team are interested in how the trial drug affects your every day life.

You will be asked to complete 4 questionnaires at each of the following times:

before treatment
at your 6 month treatment visit
every year until your treatment is finished

It takes about 10 minutes to fill them all out. You don’t have to do the questionnaires. If you say no, you can still take part in the study.

Hospital visits

You see the doctor and have tests before you can take part. These include:

a physical examination including a breast examination
vital signs (temperature, pulse, blood pressure )
mammogram or MRI scan
bone density scan (DEXA scan)
blood tests
a pregnancy test if there is any chance you could become pregnant

You go to the hospital once every 6 months to see the team and have your injection. You have your injection as an outpatient and each visit takes around an hour.

You also have some tests and scans while having treatment. They include:

a physical examination and vital signs before each treatment
a breast examination once a year
a mammogram or MRI scan once a year. This is your usual breast screening.
pregnancy tests every 3 months. You can do this at home when you are not at the hospital for treatment.
blood tests once a year
a bone density scan (DEXA) 3 to 6 months after you finish treatment

Side effects

The trial team monitor you during treatment and afterwards. Tell your doctor or nurse if any side effects are bad or not getting better.

The most common side effects of denosumab are:

low level of calcium or phosphorus in the blood
shortness of breath
muscle or bone pain
damage to your jaw bone - signs include ongoing jaw pain, swelling, numbness or a heavy feeling in the jaw. Tell your doctor or nurse straight away if this happens.
hair loss

We have more information on the side effects of denosumab.

Calcium and vitamin D Supplements.
Your doctor might recommend that you to take calcium and vitamin D supplements while taking part in the trial. These supplements generally do not cause side effects. Your doctor will talk to you about the benefits and risks of taking these supplements.