A trial looking at trastuzumab deruxtecan for breast cancer (DESTINY Breast06)

Please note - this trial is no longer recruiting patients. We hope to add results when they are available.

Cancer type:

Breast cancer

Secondary cancers

Status:

Closed

Phase:

Phase 3

This trial is comparing trastuzumab deruxtecan with chemotherapy for breast cancer that has spread.

It is open to people whose cancer got worse while having hormone treatment Open a glossary item and the cancer has:

spread from the breast into the surrounding area (locally advanced breast cancer ) or
spread to another part of the body (secondary breast cancer )

And your breast cancer must:

have a small number of HER2 receptors
hormone receptor positive

More about this trial

Doctors can treat breast cancer spread with chemotherapy. Researchers think that trastuzumab deruxtecan might help treat breast cancer that has spread. They aren’t sure how well it works for people with low levels of HER2 on their breast cancer cells. So they are running this trial to find out more.

Trastuzumab deruxtecan is a combination of 2 drugs. Trastuzumab is a targeted drug called a monoclonal antibody. It attaches to the HER2 protein Open a glossary item on the cancer cells. It then releases deruxtecan into the cancer cell. Deruxtecan or DXd is the chemotherapy part of the drug. It kills or damages the cancer cell.

In this trial half the people have trastuzumab deruxtecan. And the other half have standard chemotherapy. Open a glossary item

The chemotherapy you have is one of the following:

paclitaxel
capecitabine
nab paclitaxel

Your doctor will choose the one that is best for you.

The aims of this trial are to find out:

how well trastuzumab deruxtecan works for people with low levels of HER2 on their breast cancer cells
more about the side effects
how it affects 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:

have locally advanced breast cancer or your cancer has spread to another part of the body (secondary breast cancer)
have cancer that has the hormone receptors for oestrogen (ER positive), progesterone (PgR positive) or both
have cancer that has low or very low amounts of HER2
have a sample of tissue (biopsy ) from where your cancer has spread to that the team can access. If this isn’t available you are willing to have a new sample taken.
have cancer that has got worse while having treatment or after treatment
have had 2 courses of treatment with hormone therapy and your cancer has got worse
have an area of cancer that the doctor can measure on a scan
have had a test that shows your heart works well enough to take part in the trial. Your doctor will arrange the test and let you know the result.
can have at least one of these chemotherapy drugs in the trial. These include capecitabine, paclitaxel or nab paclitaxel.
have satisfactory blood test results
are able to look after yourself but might not be able to do heavy physical work (performance status 0 or 1)
are willing to use reliable contraception during treatment and for some time after if there is any chance you or your partner could become pregnant
are at least 18 years old

Who can’t take part

Cancer related

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

have cancer spread to the brain or spinal cord unless it is stable and doesn’t need treatment
have an area of cancer that is pressing on your spinal cord (spinal cord compression )
have ongoing side effects from previous treatment. Unless they are mild.
are having treatment for your cancer. This includes an experimental drug as part of another clinical trial.
have already had treatment with a drug that blocks HER2 such as trastuzumab
have had chemotherapy for advanced breast cancer
have had radiotherapy within 4 weeks of going into a treatment group (randomisation ). This includes palliative radiotherapy to the chest. For palliative radiotherapy to other parts of the body it is 2 weeks.
have had hormone therapy within 3 weeks of randomisation
have had chloroquine or hydroxychloroquine within 2 weeks of randomisation
are sensitive or allergic to the drugs used in this trial or any of their ingredients. You are sensitive or allergic to any other monoclonal antibody .
have had another cancer within the past 3 years. This is apart from successfully treated non melanoma skin cancer , in situ carcinomas , any other solid cancer or cancer that was in the opposite breast.
have had another monoclonal antibody that has a chemotherapy drug attached to it that blocks certain substances. Your doctor will know if you have had one of these.
have taken part in another trastuzumab deruxtecan trial. This is regardless of whether you had trastuzumab deruxtecan or not.

Medical conditions

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

have major surgery within 4 weeks of randomisation
have had a heart attack within the past 6 months or any other heart problem that might affect you taking part
have uncontrolled high blood pressure
have lung problems or lung disease that could affect you taking part. This includes an autoimmune disease that affects the lungs.
have an infection that needs treatment through a drip (intravenous infusion )
have HIV, hepatitis B, hepatitis C or any other disease that affects how well the immune system works
are taking medication that damps down the immune system within 2 weeks of starting treatment. This is apart from nasal sprays, inhalers and a small dose of steroids.
have any other medical condition or mental health problem that could affect you taking part

Other

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

have a live vaccine within 30 days of starting treatment. You should not have a live vaccine within 30 days after finishing treatment. This doesn’t apply to the COVID-19 vaccines as they are not live vaccines.
are pregnant or breastfeeding

Trial design

This is an international phase 3 trial. The team need 850 people to join with 35 people from the UK.

It is a randomised trial. Neither you nor your doctor can choose which group you go into. There are 2 treatment groups:

trastuzumab deruxtecan
standard chemotherapy

Diagram 1

You have trastuzumab deruxtecan as a drip into a vein. You have it once every 3 weeks. Each 3 week period is a cycle of treatment Open a glossary item . You have your first dose of trastuzumab deruxtecan over 90 minutes. If you have no reactions during the first dose the rest of your treatment is over 30 minutes.

There are 3 standard chemotherapy drugs your doctor can choose from:

Your doctor will talk to you about which is the best for you.

You have paclitaxel as a drip into a vein. You have it once every 3 weeks. This is a cycle of treatment.

Capecitabine is a tablet. You take it twice a day for 2 weeks and then don’t take it for a week. Each 3 weeks is a cycle of treatment.

You have nab paclitaxel as a drip into a vein. You have it once a week for 3 weeks and then have no treatment for a week. This is a 4 week cycle of treatment.

You continue to have treatment as long as it is working and the side effects aren’t too bad.

Quality of life
You fill in a few questionnaires:

before starting treatment
at regular times during treatment
after treatment

The questions ask about:

your general health
your daily activities
side effects and symptoms

These are quality of life questionnaires.

Research samples
The team take extra blood samples during the trial. Where possible they will take them when you have your routine blood samples taken.

Researchers will use these blood samples to look for:

small pieces of cancer DNA (ctDNA )
changes in the genes of the cancer cells
substances (biomarkers ) that might show how well treatment is working

The team ask for a piece of a previous tissue sample (biopsy). If this isn’t available you must give a new tissue sample. They use these samples to:

check the level of HER2 receptors on your breast cancer cells
look at the genes in the cancer cells
look for biomarkers

The team would also like to collect a tissue sample if your cancer gets worse during treatment or in the future.

Some of these samples you must agree to and some you don’t have to. Your doctor or a member of the team will talk to you about this.

Hospital visits

You see the doctor to have tests before taking part. These tests include:

a physical examination
blood tests
heart trace (ECG )
heart scan (ECHO or MUGA )
eye test
CT scan or an MRI scan
bone scan only if your cancer has spread to the bones
breathing tests (lung function tests )

You see the doctor at regular times during treatment. This is to see how you are and for blood samples. You also have regular heart scans and heart traces while having treatment.

You have a CT scan or an MRI scan:

every 6 weeks for 48 weeks and then
every 9 weeks.

You see the doctor just over a month after you finish treatment for the same tests you had at the start.

You then see the doctor every 3 months.

Side effects

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

The most common side effects of trastuzumab deruxtecan are:

feeling or being sick
tiredness and or feeling weak (fatigue)
loss of hair
constipation or diarrhoea
a drop in blood cells causing an increased risk of infection, bruising and bleeding
loss of appetite
coughing, difficulty breathing, changes to the lungs such as inflammation and scarring
stomach (abdominal) pain
headache
sore mouth or mouth ulcers
a change to how your liver works
low level of potassium in the blood
severe nosebleeds
high temperature (fever) with a low number of white blood cells called neutrophils
a reaction while having trastuzumab deruxtecan
indigestion
dry eyes
infection of the nose, throat and upper chest
dizziness

It is possible that some people could have side effects that we do not know about yet.

Trastuzumab deruxtecan can cause severe lung problems. Some of which can be life threatening. You need to tell your doctor or nurse straight away if you have any of the following: