A study of durvalumab with other cancer drugs for triple negative breast cancer (BEGONIA)

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 1/2

This study is looking at durvalumab and paclitaxel combined with other cancer drugs for triple negative breast cancer that has spread.

Triple negative breast cancer is breast cancer that has no receptors for:

the hormone oestrogen
the hormone progesterone
the protein HER2

There are 2 parts to this study. This summary is about part 1.

More about this trial

Chemotherapy is the standard treatment Open a glossary item for triple negative breast cancer that has spread to another part of the body. One of the chemotherapy drugs that doctors use is paclitaxel.

Researchers are always looking for better treatments for triple negative breast cancer. In this study they are looking at combining targeted cancer drugs Open a glossary item and immunotherapy drugs with paclitaxel. The combinations they are looking at are:

durvalumab and paclitaxel
durvalumab, paclitaxel and capivasertib
durvalumab, paclitaxel and selumetinib - closed
durvalumab, paclitaxel and danvatirsen - closed
durvalumab, paclitaxel and oleclumab
durvalumab and trastuzumab deruxtecan

Durvalumab, oleclumab and trastuzumab deruxtecan are a type of immunotherapy called monoclonal antibodies (MABs). They work by helping the immune system Open a glossary item to recognise cancer cells.

Capivasertib, selumetinib and danvatirsen are a types of targeted cancer drugs called cancer growth blockers. They work by stopping cancer cells from growing or by causing cancer cells to die.

The aims of this part of the study are to find:

how well each treatment combination works for triple negative breast cancer that has spread
out more about the side effects of each treatment combination

Who can enter

The following bullet points list the entry conditions for this study. Talk to your doctor or the study 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 study if all of the following apply. You:

have triple negative breast cancer (TNBC) that has spread to another part of the body
have not had treatment for your cancer spread. If you had TNBC that was treated with the aim to cure and then it had spread, you must have completed your initial treatment such as surgery or chemotherapy at least 6 months ago. If you had a chemotherapy drug called a taxane such as paclitaxel it must have been finished at least a year ago.
are generally well and active but might not be able to do heavy physical work (performance status 0 or 1)
have satisfactory blood test results
must weigh at least 35kg
have at least 1 area of cancer that hasn’t had radiotherapy treatment and that the doctor can measure on a scan
are at least 18 years old

For part 1 of the trial only women can take part. For part 2 both women and men can take part.

Who can’t take part
You cannot join this study if any of these apply.

Cancer related
You:

have cancer that has spread to your brain or spinal cord. Unless it has been treated and you have had 2 scans (4 weeks apart) that show it is stable. You have no symptoms and aren’t taking steroids. Or have been taking 10mg or less for at least 2 weeks before taking part in the study.
have cancer that has spread to the layer of tissue (meninges) that surrounds the brain
have ongoing moderate to severe side effects from previous cancer treatment. This is apart from hair loss and vitiligo. You might be able to take part if you have ongoing nerve damage (neuropathy), or side effects that may not be made worse by the study drug, talk to your doctor or the study team about this.
are taking other cancer drugs apart from bisphosphonates and denosumab to treat cancer spread in the bone
have already had an immunotherapy cancer drug
have had radiotherapy unless it was at least 1 year ago. For radiotherapy to the brain or to control bone pain (where less than 30% of your bone marrow was affected) it is at least 4 weeks before starting the study treatment.
have had cancer growth blocker drugs
have had another cancer apart from successfully treated non melanoma skin cancer , lentigo maligna (a type of early melanoma skin cancer), carcinoma in situ . Or any other cancer that has been treated with the aim to cure and there has been no sign of it for 5 years or more.

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

have had an organ transplant
have an autoimmune disease , such as rheumatoid arthritis or systemic lupus erythematous, apart from vitiligo, hair loss or an ongoing skin condition that doesn’t need treatment that affects the whole body. You might be able to take part if you are taking thyroid hormone tablets to replace low levels of these hormones after treatment for a condition such as Hashimoto syndrome or if there has been no sign of your autoimmune disease for at least 5 years.
have an inflammatory disease such as an inflammatory bowel disease. You might be able to take part if there has been no sign of it for the past 5 years.
have an ongoing or active infection
have had a heart attack, heart surgery, chest pain (angina) or congestive heart failure in the past 6 months or you have ongoing heart problems such as uncontrolled angina or an irregular heartbeat (heart rhythm)
are at risk of developing heart problems
have an ongoing problem with your immune system or it isn’t working well enough
are taking medication, such as steroids, that affect how well your immune system works within 2 weeks of starting treatment apart from inhalers, creams, local injections (such as into the joints) or a dose of 10mg or less of steroid tablets
have tuberculosis (TB), hepatitis B, hepatitis C or HIV
have diabetes type 1 or have abnormal blood sugar levels
have had a blood clot in the past 6 months
have major surgery within 28 days of starting treatment apart from surgery to a small area (local) to relieve symptoms of bone pain
are taking vitamin E supplements, or multivitamins that contain vitamin E, that give more than 100% of the recommended daily dose of vitamin E
are taking medication that affects the CYP enzymes within 2 weeks of starting treatment (3 weeks for St John’s Wort)
have taken part in a clinical trial using an experimental drug within the past 28 days
are taking part in a clinical trial unless it is an observational study only or you are being followed up after having treatment or using a device as part of a clinical trial
are willing to use reliable contraception during treatment and for 6 months after if there is any chance you or your partner could become pregnant

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

have a live vaccine within 30 days of starting treatment. The COVID-19 vaccines are not considered to be live vaccines.
are allergic to the drugs, or any of their ingredients, used in this study
are pregnant or breastfeeding

Genetic sample research
You cannot take part in the genetic research part of the study if either of the following apply. You:

have had a donor bone marrow transplant (allogeneic transplant )
or you have had a whole blood transfusion where the white blood cells haven’t been taken out within 120 days of the team taking the sample

Trial design

There are 2 parts in this study. This is an international study.

This summary is about part 1. When part 2 opens we will include it in the summary.

Part 1
The first part is a phase 1b study.

Researchers needed 170 people worldwide to join. They have enough people for 2 treatment groups. So they now need another 110 people with 23 people from the UK.

In this part there were 6 groups but now only 4 groups are open for people to join:

20 people have durvalumab and paclitaxel (group 1)
30 people have durvalumab, paclitaxel and capivasertib (group 2)
30 people have durvalumab, paclitaxel and selumetinib (group 3) – closed
30 people have durvalumab, paclitaxel and danvatirsen (group 4) – closed
30 people have durvalumab, paclitaxel and oleclumab (group 5)
30 people have durvalumab and trastuzumab deruxtecan (group 6)

The first 20 people to join the study are in group 1.

Then everyone is put into groups 2 to 5 at random Open a glossary item .

To start with 6 people are put into each group. This is to check that the combination of drugs in each group is safe. After this another 14 people go into each group.

So which group you are in depends on when you join the study.

Group 1
You have durvalumab and paclitaxel as a drip into a vein. You have durvalumab at the start of each cycle of treatment. You have paclitaxel once a week for 3 weeks. Then you have a week of no treatment. This 4 week period is a cycle of treatment Open a glossary item .

Diagram 1

Group 2
You have durvalumab and paclitaxel as a drip into a vein. You have durvalumab at the start of each cycle of treatment. You have paclitaxel once a week for 3 weeks. Then a week of not having it. This is a 4 week cycle of treatment.

Capivasertib is a capsule you take twice a day. You take them for 4 days starting the day after having paclitaxel. You have a diary to write down when you have capivasertib.

Diagram 2

Group 5
You have durvalumab and paclitaxel as a drip into a vein. You have durvalumab at the start of each cycle of treatment. You have paclitaxel once a week for 3 weeks. Then a week of not having it. This is a 4 week cycle of treatment.

You have oleclumab as a drip into a vein. For cycle 1 and cycle 2 of treatment you have it once a week for 2 weeks. For every treatment cycle after, you have it once a week at the start of each cycle when you have durvalumab and paclitaxel.

Diagram 5

Group 6
You have durvalumab and trastuzumab deruxtecan as a drip into a vein. You have them both on the same day. You have them once every 3 weeks. This is a 3 week cycle of treatment.

Diagram 6

For all the groups you can continue having treatment as long as it is helping and the side effects aren’t too bad.

Research samples
During the study you give blood and tissue samples for research. You have these as part of your normal routine care. They will use these samples to find out how well the treatment is working and to look for substances (biomarkers Open a glossary item ) that can tell them how well the treatment is working.

They will also ask for extra tissue samples:

from when you were first diagnosed
during the study
if your cancer gets worse

They will also ask for extra blood samples during the study.

Researchers will use these samples to look at the genes in the cells to find out what difference they make to how well the treatment works. They will also help to find out more about the cancer.

You don’t have to agree to have these extra samples taken. You can still take part in the main study.

The researchers will store any samples for future research. You don’t have to agree to this. You can still take part in the main study.

Hospital visits

You see the doctor to have test before agreeing to take part. These tests include:

a physical examination
blood tests
urine test
heart trace (ECG )
heart scan (ECHO )
a scan such as a CT scan, an MRI scan, a PET-CT scan or a bone scan

For people in group 6 only you also have:

a breathing test (lung function test)
eye test
CT scan of the lung

During treatment you see the doctor regularly. Your doctor or the study team will tell you how often this is.

You see the doctor at the end of treatment for:

a physical examination
blood tests
urine test
a scan (the same you had at the start)
heart scan (if needed)

You then see the doctor as part of the study:

every month for 3 months
then at 6 months
then the team call you every 3 months

Side effects

You are monitored closely for side effects when having treatment as part of the study. Contact your advice line or tell your doctor or nurse if any side effects are bad or not getting better.

Durvalumab, capivasertib, oleclumab and trastuzumab deruxtecan are new drugs and there might be side effects we don’t know about yet. There might also be side effects from the combination of drugs they are looking at in this study that we don’t know about yet.

Durvalumab and oleclumab can affect the immune system. They may cause inflammation in different parts of the body. This can cause serious side effects. These could happen during treatment, or some months after treatment has finished. Rarely, these side effects could be life threatening.
If you have any of these side effects tell your doctor or nurse as soon as possible. You should tell them that you are on or have been on an immunotherapy.

The most common side effects of durvalumab include:

diarrhoea
rash, dry, itchy skin
problems with how your liver works
tiredness (fatigue)
feeling or being sick
tummy (abdominal) pain
swelling due to your body holding more fluid
infection of the sinuses, throat, airways and lungs
loss of appetite
shortness of breath
cough
painful muscles and joints
high temperature (fever)

The most common side effects of capivasertib include:

an allergic reaction
an increase in the level of glucose in the blood
loss of appetite
diarrhoea
feeling or being sick
redness and swelling of the mouth and lips
rash, dry, itchy skin

The side effects of durvalumab and oleclumab combined include:

tiredness (fatigue)
diarrhoea or constipation
feeling or being sick
tummy (abdominal) pain
high temperature (fever)
a drop in red blood cells
difficulty breathing
cough
increase in fluid around the tummy (abdomen)
loss of appetite
confusion
back pain
liver problems

The most common side effects of trastuzumab deruxtecan include:

a drop in blood cells causing an increased risk of infection, bruising and bleeding
hair loss
constipation or diarrhoea
loss of appetite
feeling or being sick
stomach (abdominal) pain
sore mouth and mouth ulcers
coughing
feeling tired and weak (fatigue)
severe nose bleeds
dizziness
dry eyes
a low level of potassium in the blood
difficulty breathing
infections of the mouth, nose, throat and upper chest
a change to the way the liver works

Trastuzumab deruxtecan might cause a serious lung problem. In some cases this could be life threatening. Symptoms are similar to other heart or lung diseases. Please contact your doctor straight away if you have any new lung symptoms or symptoms that are getting worse. These include: