A trial of AZD9833 for breast cancer (SERENA-4)
Please note - this trial is no longer recruiting patients. We hope to add results when they are available.
Cancer type:
Status:
Phase:
This trial is looking at a new drug called AZD9833 for breast cancer that has come back or spread to another part of the body.
It is for people whose cancer has:
- a lot of hormone receptors (
hormone receptor positive 
) - and only a small number of receptors for
HER2 (HER2 negative)
More about this trial
Doctors can treat hormone receptor positive breast cancer that has come back or spread with the combination of anastrozole and palbociclib.
Oestrogen is the female sex hormone. It encourages hormone receptor positive breast cancer to grow. Anastrozole lowers the level of oestrogen in the body. This can stop or slow the growth of the cancer.
Palbociclib is a called a cancer growth blocker. There are proteins on the cancer cells (CDK4 and CDK6). These proteins stimulate the cancer cells to grow and divide. Palbociclib blocks these proteins. This can stop or slow the growth of the cancer.
AZD9833 is selective oestrogen receptor degrader (SERD). It works by breaking down the site where oestrogen attaches to the cancer cell. This can help stop or slow the growth of hormone receptor breast cancer.
Researchers think that AZD9833 with palbociclib might work better than anastrozole and palbociclib.
In this trial there are 2 treatment groups:
- AZD9833, palbociclib and a dummy drug (
placebo ) - anastrozole, palbociclib and a dummy drug
The team use the dummy drug so you won’t know which treatment you are having.
The aims of this trial are to find out:
- whether AZD9833 with palbociclib is better than anastrozole with palbociclib
- about the side effects of combining AZD9833 with palbociclib
- how the combination 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 breast cancer that has come back in the same area or has spread to another part of the body
- have cancer that has a large number of oestrogen receptors (is ER positive) and not very many HER2 receptors (it is HER2 negative)
- have cancer that can’t be treated with the aim to cure with radiotherapy or surgery
- have an area of cancer that the doctor can see on a scan and measure
- have had an
aromatase inhibitor for at least 2 years and it has been at least a year since your last dose, or you have had tamoxifen as part of your treatment for at least 2 years and you stopped taking tamoxifen at least 2 weeks before joining the trial. You can also join the trial if you haven’t had any treatment at all for your cancer that has spread to another part of the body. - are active but might not be able to do heavy physical work (performance status 0 or 1)
- have satisfactory blood test results
- weigh at least 35kg (77lbs)
- are willing to use 2 forms of contraception that are not hormone based during the trial and for some time after if there is any chance you or your partner could become pregnant
- have a sample of tissue (
biopsy ) from where the cancer came back or where it has spread available for the team. If this isn’t available you are willing to have a new biopsy taken from where the cancer came back or has spread to. - are at least 18 years old and able to give
informed consent
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. You might be able to join if you have had treatment and you have not taken any medication for the spread within 4 weeks of
randomisation . - are already having treatment for your cancer
- have had an aromatase inhibitor and the cancer came back while still having treatment or within a year after completing treatment
- have ongoing side effects from previous treatment. This is apart from mild side effects and hair loss.
- have
palliative radiotherapy for symptom control such as pain within 2 weeks of starting trial treatment. You can’t join If you have radiotherapy to a wide area or if the radiotherapy includes more than 30% of your bone marrow within 4 weeks of starting trial treatment. - have another cancer unless it has been treated with the aim to cure and there hasn’t been any sign of it for at least 3 years. This is apart from successfully treated
non melanoma skin cancer , a type of melanoma called lentigo maligna and in situ carcinoma of the cervix.
Medical conditions
You cannot join this trial if any of these apply. You:
- have HIV or active hepatitis B or hepatitis C
- have
heart problems such as a heart attack or chest pain (angina). This includes some heart surgery. You cannot join if your heartbeat at rest is less than 60 beats a minute. - have had a stroke or mini stroke within the 6 months of starting trial treatment
- have uncontrolled high blood pressure or you have low blood pressure
- have fainting episodes that can’t be explained
- have poor eyesight unless it can be treated or corrected
- have a problem with your
digestive system . This includes uncontrolled nausea , uncontrolled vomiting or an ongoing problem that could affect how well your body absorbs medication taken by mouth. - have had medications or herbal supplements that affect the CYP enzymes within 2 weeks of randomisation. This includes warfarin and phenytoin.
- have had major surgery or a major injury within 4 weeks of starting trial treatment. You can’t join if you might need to have major surgery or surgery using a general anaesthetic during the trial.
- have had an experimental drug or used an experimental device within 4 weeks of randomisation.
- have already had AZD9833
- are allergic or very sensitive to any of the drugs used in the trial or any of their ingredients
- have any other medical condition or mental health problem that your doctor or the trial team thinks could affect you taking part
Other
You cannot join this trial if you are pregnant or breastfeeding.
Trial design
This is an international phase 3 trial. The team need 1,342 people to join with 30 people from the UK.
It is a randomised double blind trial. There are 2 treatment groups. Neither you nor your doctor can choose which group you are in. And neither you nor your doctor will know which group you are in.
Your doctor will be able to find out what treatment you are having if this becomes necessary during the trial.
The 2 treatment groups are:
- anastrozole, palbociclib and a dummy drug (placebo)
- AZD9833, palbociclib and a dummy drug
AZD983 is a tablet. You take it once a day every day.
Anastrozole is a tablet. You take it once a day every day.
Palbociclib is a capsule or tablet. You take it once a day for 3 weeks. Then you have a week when you don’t take it. This is a . You then continue taking it like this, 3 weeks when you are taking palbociclib and then a week off.
The dummy drugs are tablets. You take the once a day every day.
You continue taking the treatment for as long as it is helping and the side effects aren’t too bad.
For some women and some men
You also have if you are:
- are a woman who has not started the menopause (pre menopausal)
- are a woman who is still having periods and has started the menopause (peri menopausal)
- a man who hasn’t had surgery to remove his testicles
Luteinising hormone release hormone (LHRH) blockers stop the body making the sex hormones. This is important because sex hormones can stop the treatment working as well as possible.
Your doctor will talk to you about which LHRH blocker is best for you. You have it as an injection under the skin. You have your first injection before or on the same day you start your treatment. You continue to have it once a month while having the trial treatment.
Quality of life
You fill in questionnaires:
- before you start treatment
- at regular times while still having treatment
- at the end of treatment
The questions ask about:
- your general health
- what daily activities you can do
- any side effects
- whether you have had extra visits to your doctor or the hospital
These are quality of life questionnaires.
Research samples
You give extra blood samples during treatment. Where possible the team takes them when you have your routine bloods taken.
The team use these blood samples to find out what happens to the treatment in the body and how it affects the body. They will also look for small pieces of the cancer DNA ().
You have a sample of tissue (biopsy) taken from where the cancer came back or has spread to if there isn’t a previous one available for the team to access. You must agree to this to take part in the trial.
The team also ask for other tissue samples:
- a small piece of the biopsy taken from the original cancer when you were first diagnosed if you have already had treatment for your cancer. You don’t have a fresh biopsy taken for this.
- a new biopsy taken while you are having the trial treatment
- a new biopsy taken if your cancer gets worse while having treatment
You don’t have to agree to these 3 samples. You can still take part in the trail.
The team use the tissue samples to find out:
- more about breast cancer and its treatment
- how well the treatment is working
- understand why treatment isn’t working
Hospital visits
You see the doctor to have tests before taking part. These tests include:
- a
physical examination - blood tests
- a fresh sample of tissue (biopsy) of where the cancer came back or spread. Only if a sample was not taken before or the team can’t access it.
- heart trace (
ECG ) - heart scan (
ECHO ) - eye examination
- CT scan or an MRI scan
- bone scan
You see the doctor every 2 weeks for 8 weeks. This is to see how you are and for bloods. After this you see the doctor every 3 months while having treatment. Between seeing the doctor you go to the hospital to collect your drug and for blood tests.
About 4 weeks after stopping treatment you see the doctor and have the same tests you had at the start.
You then either see the doctor at the hospital or your GP or your doctor might call you on the phone every 3 months. This to see how you are and ask whether you have started any more treatment.
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.
There may be side effects we don’t know about AZD9833 either used by itself or in combination with other medication.
The common side effects of AZD9833 we do know about are:
- changes to how your heart works such as slowing of the heart rate
- eye problems such as after images, flashing lights and trailing of lights
- affecting how other drugs for example warfarin work in the body
We have information about:
Your doctor or a member of the trial team will talk to you about the side effects of the treatments used in this trial before you agree to take part.
Recruitment start:
Recruitment end:
How to join a clinical trial
Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.
Chief Investigator
Dr Richard Baird
Supported by
AstraZeneca
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
