A trial of camizestrant for breast cancer (SERENA 6)

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

Cancer type:

Breast cancer

Status:

Closed

Phase:

Phase 3

This trial is looking at camizestrant (AZD9833) with a targeted cancer drug Open a glossary item for breast cancer. It is for people with breast cancer that has come back in the same area or spread to another part of the body.

It is open to people with breast cancer who are doing well on their current treatment and their cancer has:

a large number of receptors for the hormone oestrogen (ER positive ) and
a small number of the HER 2 protein (HER 2 negative)

More about this trial

Doctors can treat ER positive and HER 2 negative breast cancer with an aromatase inhibitor Open a glossary item combined with a targeted drug.

Letrozole and anastrozole are aromatase inhibitors. They work by lowering the amount of oestrogen in the body. ER positive breast cancer needs oestrogen to grow. Lowering the amount of oestrogen can slow or stop the cancer growth.

Abemaciclib , palbociclib and ribociclib are targeted drugs called cancer growth blockers. They work by blocking substances that cancer cells need to grow.

In this trial researchers are looking at a treatment called camizestrant (AZD9833). It works by blocking oestrogen getting into the breast cancer cell. This then can stop or slow the cancer growth.

This trial has 2 steps.

In the first step you have the standard treatment Open a glossary item . Your doctor decides which one. This can be either letrozole or anastrozole with abemaciclib, palbociclib or ribociclib.

During this step you give regular blood samples. The team use these samples to look for a change (mutation Open a glossary item ) in the ESR1 gene . They do this by looking for small pieces of the cancer DNA in the blood (ctDNA ).

This gene change can happen while you are having treatment. If one of your blood samples show you have a change in ESR1 the team might invite you to take part in step 2, the treament stage.

In the treatment stage you have either:

abemaciclib, palbociclib or ribociclib, camizsterant and a dummy drug (placebo )
or
abemaciclib, palbociclib or ribociclib, letrozole or anastrozole and a dummy drug

SERENA 6 flow chart diagram

The aims of this trial are to find out:

whether camizestrant with a targeted drug is better than an aromatase inhibitor with a targeted drug
how safe it is to have camizestrant with a targeted drug
how it affects quality of life
whether using ctDNA can tell how well AZD9833 is working

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

There are 2 steps in this trial.

Step 1
You may be able to join step 1 if all of the following apply. You:

have adenocarcinoma of the breast that has come back in the same area or has spread to another part of the body
can’t have surgery or radiotherapy with the aim to cure your cancer
have cancer that has a large number of oestrogen receptors (ER positive ) and not many HER2 proteins (HER2 negative)
are taking letrozole or anastrozole. And you have been taking them for at least 6 months. If you are also taking medication to block the sex hormones (LH blockers ) you must agree to continue with them while in the trial.
are taking a targeted drug such as palbocicilib, abemaciclib or ribociclib. And you have been taking them for at least 6 months.
have no sign that the cancer is getting worse
are willing to let the trial team access any previous scans of your cancer
can look after yourself but might not be able to do heavy physical work (performance status 0 or 1)
weigh at least 35kg (5st 5lb)
are willing to use reliable contraception during the trial and for a time after if there is any chance you or your partner could become pregnant
are at least 18 years old

Treatment stage (Step 2)
You may be able to join the treatment stage if all of the above apply and:

a blood sample from step 1 shows your cancer has the ESR1 gene change
you are on the same treatment when you joined step 1
your cancer hasn’t got worse
you have an area of cancer that the doctor can measure on a scan
you are willing to allow the trial team to access any previous tissues samples you have had
you have satisfactory blood test results

Who can’t take part

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

You are having hormone therapy by itself.
There is no sign of cancer. You might be able to join if your cancer has spread to the bones. Your doctor will know about this.
You have cancer spread that might be life threatening. For example you have large amounts of fluid around the heart, lungs or tummy (abdomen) that isn’t controlled. Or the cancer has spread to the lymph nodes and lymph tubes (lymphatic system ) of the lungs.
You have cancer spread to the brain or spinal cord. Unless it has been treated, it is stable and you aren’t taking any medications for it.
You have had another cancer. This is apart from successfully treated non melanoma cancer , lentigo maligna melanoma or in situ carcinoma of the cervix. You can join if you had cancer at least 3 years ago that was treated with the aim to cure. As long as there hasn’t been any sign of it since and it is unlikely to come back.

You can’t join the treatment stage if any of the following also apply. You:

have no sign of cancer or if the only sign of cancer is abnormal growth in your bones when your doctor considers you for this stage
are generally very unwell
are having any other type of cancer treatment
have ongoing side effects from treatment. This is apart from certain ones that your doctor will know about.

Medical conditions
You cannot join step 1 of this trial if any of these apply. You:

can’t swallow tablets or capsules
have a problem with your digestive system that affects how well you absorb tablets or capsules
have moderate to severe lung problems as a side effect of having a targeted cancer drug that is a CDK4 or CDK6 inhibitor. Your doctor will know about this.
have a severe heart problem or a member of your family does
have had heart surgery within the past 6 months
have a first degree relative such as brother, sister or parent who died under the age of 40 and their death was sudden and unexplained
have already had camizestrant or any other experimental hormone therapy
have had fulvestrant
are taking part in another clinical trial unless you are in follow up or it is an observation study
have another medical condition or mental health problem that could affect you taking part

You can’t join the treatment stage if any of the following also apply. You:

have HIV unless it is controlled and you haven’t had any opportunistic infections in the past year
have hepatitis B, hepatitis C, tuberculosis (TB) or any other active infection
have fainting episodes that can’t be explained
have low blood pressure or uncontrolled high blood pressure
have heart problems . You might be able to join if you have a pacemaker. Your doctor will know about this.
have a heartbeat of less than 60 beats per minute at rest
are taking hormone replacement therapy (HRT) for another reason other than cancer
have radiotherapy for symptom control (palliative) to a small area within 2 weeks of starting treatment. For a large area or if more than 30% of bone marrow is in the treated area it is 4 weeks.
have major surgery or a major injury within 4 weeks of being put into a trial treatment group (randomisation )
have taken medication that affects the CYP enzymes within 2 weeks of randomisation. This includes herbal treatments. Your doctor will know which meidcations and herbal treatments these are.
have had an experimental drug or used an experimental device as part of another clinical trial within 4 weeks of randomisation

Other
You can’t join the trial if any of the following also apply. You are:

pregnant or breastfeeding
allergic or sensitive to any of the drugs used in the trial or any of their ingredients

Trial design

This is an international phase 3 trial. There are 2 steps to this trial.

For step 1 the team need 3,050 people to take part with about 107 people from the UK.

For the treatment stage (step 2) the team need 300 people to take part with 16 people from the UK.

Step 1
In step 1 everyone takes letrozole or anastrozole with either abemaciclib, palbociclib or ribociclib. You give a blood sample every 8 to 12 weeks.

The team use the blood samples to look for the gene change (mutation Open a glossary item ) in ESR1. They do this by looking for small pieces of the cancer DNA (ctDNA ) in the blood.

If one of your blood samples show the ESR1 gene change you might be invited to take part in the treatment stage of the trial.

You continue giving blood samples and being a part of step 1 until:

your sample shows the ESR1 gene change or
the team have enough people in the treatment stage

Researchers use the blood samples to:

look for several cancer gene changes including ESR1
develop ctDNA testing for approval so doctors can use it in the future
understand the cancer better including how well treatment is working

Treatment stage
In this stage the team are looking at whether swapping letrozole and anastrozole with camizestrant works better. You continue to have the targeted drug, that is palbociclib, abemaciclib or ribociclib.

This is a randomised double blinded trial. A computer puts you into 1 of 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 which group you are in if it is necessary to do so.

The groups are:

palbociclib, abemaciclib or ribociclib with camizestrant and a dummy drug (placebo )
palbociclib, abemaciclib or ribociclib with letrozole or anastrozole and a dummy drug

SERENA 6 randomisation diagram

Camizestrant is a tablet. You take it once a day every day.

Letrozole is a tablet. You take it once a day every day.

Anastrozole is a tablet. You take it once a day every day.

Abemaciclib is a tablet. You take it once a day every day.

Palbociclib is a tablet. You take it once a day every day for 3 weeks. Then for the next week you don’t take palbociclib. You continue having palbociclib like this.

Ribociclib is a tablet. You take it once a day every day for 3 weeks. Then for the next week you don't take ribociclib. You continue having ribociclib like this.

The dummy drugs are tablets. You take them once a day every day.

You continue with treatment as long as it is helping and the side effects aren’t too bad.

Luteinising hormone blockers (LHRH)
Women who haven’t gone through the menopause and men who haven’t had their testicles removed by surgery will need to have a luteinising hormone blocker.

LHRHs stops the ovaries and testes from working. This stops them producing the sex hormones, testosterone in men and oestrogen and progesterone in women. These hormones can help the cancer to grow.

You have LHRH as an injection under the skin or an injection into a muscle. You start LHRH before starting treatment. And then you have it every 4 weeks. You continue while you are having treatment.

If you are already on LHRH you might need to change to another one. Your doctor will tell you if this is the case.

Samples for research
The team take several blood samples during the trial. How many depends on how long you are in the trial and what treatment you have.

In step 2 the team ask for a piece of tissue from a previous sample of tissue (biopsy Open a glossary item ). They also ask for a biopsy during treatment and when your cancer starts to grow again.

Some of these samples you must agree to and some you don’t have to. The doctor or a member of the trial team will tell you which ones they are.

Quality of life
In step 2 you fill in several forms:

when you start treatment
during treatment
at the end of treatment
and during the follow up

The questions ask about:

your general health
what daily activities you can do
side effects
symptoms

These are quality of life questionnaires.

Hospital visits

You see the doctor for tests before taking part in each step.

Step 1
In step 1 the tests include:

blood tests
CT scan or MRI scan

You continue to be a part of step 1 and having bloods taken every 8 to 12 weeks until:

the trial team detect the ESR1 gene change or
there are enough people in step 2

Treatment stage
Before taking part in the treatment stage you have the following tests:

a physical examination
blood tests
CT scan or MRI scan
urine test
heart trace (ECG )
heart scan (ECHO )
bone scan
eye examination

While having treatment as part of step 2 you see the doctor regularly. This is for blood tests and to see how you are.

You see the doctor when you finish treatment and a month later to see how you are. The trial team may contact you up to every 8 weeks until your cancer gets worse.

You have a CT scan or MRI scan every:

8 weeks for 18 months and then
every 12 weeks till your cancer starts to grow

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.

Camizestrant is a new drug and there might be side effects we don’t know about yet. The side effects we do know about are:

slowing down of the heartbeat
changes to eyesight including trailing or flashing lights on the edge of the field of vision and continuing to see the image of something after you have stopped looking at it (after images)

We have information on:

Your doctor will talk to you about the side effects of the treatments before you agree to take part.