A trial using a blood test to find certain gene changes and decide treatment for advanced breast cancer (plasmaMATCH)

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 2

This trial is looking at different treatment options for women with certain rare gene changes (mutations). It is for women whose breast cancer:

has come back (is recurrent or locally advanced breast cancer) or
has spread to another part of the body (secondary breast cancer)

Cancer Research UK supports this trial.

More about this trial

The usual way to find gene changes (mutations) in breast cancer cells is to look at a tumour sample taken during surgery or a biopsy.

Finding gene changes helps doctors to target and try to kill, or stop the cancer cells growing. But mutations can change after treatment or when cancer spreads. And it isn’t always possible to take further biopsies from people with advanced cancer.

So the choice of targeted treatment is often based on the mutations found in the original breast cancer tissue samples. These might be different to the mutations found in advanced breast cancer.

Cells within the body contain genetic information stored in the form of DNA. Breast cancers can release DNA into the bloodstream. This is called circulating tumour DNA or ctDNA. In this trial, researchers plan to:

use a blood test to look for and analyse ctDNA to find these mutations
fit treatment to the gene changes they are looking for

Using blood samples to look DNA or cancer cells is sometimes called a liquid biopsy.

The trial team are looking for rare mutations in ctDNA. So the chance of finding one of these mutations in your blood sample is small. They think that about 1 in 5 women will have a mutation and possibly be suitable to have treatment as part of this trial. If you are suitable, and have a mutation identified in ctDNA you will be put into a treatment group depending on the mutation you have.

Women who do not have a mutation identified in ctDNA but who do have a type of breast cancer called triple negative breast cancer may also enter a treatment group.

There were 5 treatment groups available in this trial. But 4 out of the 5 groups are closed. It is now open only to women with triple negative breast cancer (group E).

If you do not have one of these mutations, or you do not have triple negative breast cancer, your doctor will discuss other treatment options available outside of the trial.

The main aims of the trial are to find out:

if the blood test is a reliable way of finding gene changes compared with taking a biopsy
how well the treatment choices work
if the treatment choices are safe

Please note - the changes (mutations) the researchers are looking at in this trial are not ones that can be passed on to your family (hereditary genetic mutations).

In December 2019 the research team presented the results so far for this trial. There is more information in the ‘trial design’ section below.

Who can enter

The following bullet points list 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.

You might be able to join this trial to have your blood sample tested if all of the following apply:

you are a woman with advanced invasive breast cancer
you had a scan that showed that your cancer has come back or spread elsewhere in the body or your doctor suspects the cancer is getting worse after your last treatment
your cancer can’t be removed with surgery or treated with the aim to cure
you have had at least 1 type of treatment for advanced breast cancer or your cancer has come back within a year of having chemotherapy
if you have HER2 positive breast cancer, your cancer has come back after 2 different types of treatment (or 1 type if there aren't further types available where you are being treated
it is possible to take a sample of tissue (biopsy) of the cancer that has come back or a sample has been taken previously
you are well enough to be up and about for at least half the day (performance status 0,1 or 2)
you are at least 18 years old

Who can’t enter

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

had more than 2 courses of chemotherapy for advanced breast cancer
have cancer that has spread to your brain or spinal cord and is causing symptoms - you might be able to take part if cancer spread to your brain was treated, is stable and you aren’t taking steroids
have problems with your heart, such as a heart attack in the last 6 months, angina that is not well controlled, an abnormal rhythm of your heart or congestive heart failure
have side effects from past treatment (apart from hair loss) unless they are mild
have had any other cancer in the last 3 years apart from non melanoma skin cancer or carcinoma in situ of the cervix (CIS)
have any other medical condition or mental health problem that the trial team think could affect you taking part
are pregnant or breastfeeding

If the circulating tumour DNA blood test shows that you have one of the rare mutations that the trial team are looking for, you might be able to join one of the treatment groups within this trial. As well as the main entry conditions above, there are a number of other conditions for each of the treatment groups that must also apply.

Women who do not have a mutation identified in ctDNA but who do have a type of breast cancer called triple negative breast cancer may also enter a treatment group. They have to have treatment targeting this type of breast cancer.

Who can join a treatment group

You might be able to join one of the treatment groups within this trial if all of the following apply.

You:

had a scan that showed your cancer got worse after your last treatment
haven't had more than 2 courses of chemotherapy for advanced breast cancer
have satisfactory blood test results
are willing to use reliable contraception during the trial and for 6 months afterwards if there is any chance you could become pregnant

Who can’t join a treatment group

You cannot join one of the treatment groups if any of these apply. You:

have had any treatment for your cancer (apart from radiotherapy to help with symptoms) in the last 4 weeks (6 weeks if you had chemotherapy drugs called nitrosoureas or mitomycin C). You might be able to take part if you are having hormone therapy to stop the ovaries working and treatment such as bisphosphonates for cancer spread to the bone
are sensitive to any of the trial treatments you are going to have or anything they contain
are going to have tablets and you have a problem with your digestive system such as ulcerative colitis and you can’t absorb them properly
are going to require injections but are unwilling to have them
have had major surgery within 4 weeks of starting treatment in this trial

Group E is the only group people can join at the moment. But you won’t be able to join group E if, as well as the points above, you:

don’t have triple negative breast cancer
have a problem with blood clotting and you are having treatment
have had a bone marrow transplant with somebody else’s cells
have had a blood transfusion in the last 4 months
have had olaparib, AZD6738 or similar drugs in the past
are taking any medication that blocks an enzyme called CYP3A4
have a condition myelodysplastic syndrome or acute myeloid leukaemia (AML)
have a problem with your immune system such as HIV or active hepatitis
have an abnormal heart rhythm or a condition called Torsades de Pointes or you have a problem with the function and pumping action of your heart

Trial design

This phase 2 trial is based in the UK. The trial team will invite about 1,150 women with advanced breast cancer to have the ctDNA blood test to look for a number of genetic changes (mutations). If you have one of the mutations, you might be suitable to have treatment as part of this trial.

About 130 patients with a suitable mutation will be able to enter a treatment group. In addition, about 70 patients who do not have a mutation identified in ctDNA but who do have triple negative breast cancer will be invited to a treatment group. They have treatment targeted to this type of breast cancer.

It takes about 2 weeks to get the result of the blood test. If you don’t have the mutations, and if you do not have triple negative breast cancer, you won’t be able to join a treatment group within this trial. Your doctor will talk to you about other treatment options.

The treatments in this trial are:

fulvestrant (more often than the usual dose)
neratinib
capivasertib (AZD5363)
ceralasertib (AZD6738)
olaparib

Which treatment you have will depend on which genetic mutation and type of breast cancer you have.

Please note, groups A, B, C and D are now closed. Group E is still open for women to join.

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Group A – fulvestrant - Closed to recruitment

Group A is for people with an ESR1 gene mutation. You have a hormone therapy called fulvestrant. It blocks the actions of the hormone oestrogen in the body. Fulvestrant is a standard treatment, but you will have it for longer than usual.

You have fulvestrant as 2 injections – 1 into each buttock. To begin with, you have fulvestrant 3 times in 15 days. After that you have it once every 2 weeks

Group B - neratinib with or without fulvestrant - Closed to recruitment

Group B is for people with a HER2 gene mutation. If you have oestrogen receptor (ER) positive cancer you have fulvestrant and a targeted therapy called neratinib.

To begin with, in cycle 1 you have 2 fulvestrant injections, two weeks apart. After that you have it once every 4 weeks.

Neratinib is a type of targeted treatment called a cancer growth blocker. You take neratinib tablets once a day, every day.

If you have oestrogen receptor negative cancer you have neratinib but not fulvestrant. You take neratinib tablets once a day, every day.

Group C – capivasertib and fulvestrant - Closed to recruitment

Group C is for people with an AKT1 gene mutation. You have fulvestrant and capivasertib (AZD5363).

To begin with you have 2 fulvestrant injections, two weeks apart. After that you have it once every 4 weeks.

Capivasertib is a targeted treatment called a kinase inhibitor. You take capivasertib tablets twice a day for 4 days, followed by 3 days with no tablets, every week.

Group D – capivasertib - Closed to recruitment

Group D is for people with an AKT or PTEN gene mutation. You take capivasertib tablets twice a day for 4 days followed by 3 days with no tablets, every week.

Group E - olaparib and ceralasertib - this part is still open for women to join

Group E is for people who don’t have any gene mutations, but have a type of breast cancer called triple negative cancer.

You have olaparib tablets twice a day, every day. And ceralasertib (AZD6738) tablets for 7 days out of every 28 days (4 weeks).

Samples for research

If you join one of the treatment groups the researchers will ask for samples of your cancer (a biopsy) that were removed when you had surgery or the biopsy you had when you were first diagnosed.

They will ask you to have another biopsy before you start treatment. If this isn’t possible, they might be able to use one taken before. They would also like to take extra blood samples. Where possible, you have these at the same time as your routine blood tests.

They plan to look at substances called biomarkers to help work out why treatment might work for some people and not for others.

Results so far
In December 2019 the research team presented some results for this trial at a conference in America. They looked at the results so far for treatment groups A, B, C and D.

They had analysed blood samples (liquid biopsies) for presence of genetic mutations in circulating tumour DNA (ctDNA) in more than 1,000 people who joined the trial.

84 people with an ESR1 gene mutation were able to take part in group A
21 people with a HER2 gene mutation were able to take part in group B
18 people with an AKT1 gene mutation were able to take part in group C
19 people with either an AKT or PTEN gene mutation were able to take part in group D

The results showed that the research team mostly found the same gene changes in the ctDNA blood test as they did in the cancer cells (tissue biopsies). They were the same for between 96% and 99% of samples, depending on the gene.

Researchers were able to analyse how the treatment was working for most of the patients entered into the treatment groups.

They found that the cancer responded to treatment in:

6 out of 74 people (8%) in group A
5 out of 20 people (25%) in group B
4 out of 18 people (22%) in group C
2 out of 19 people (11%) in group D

The research team also looked at how well certain sub groups of cancer responded to treatment in each group.

The team concluded that:

testing blood samples for rare genetic changes could be a less invasive way to help decide which treatment to give people
extended dose fulvestrant may not be a useful treatment for people with an ESR1 gene mutation
fulvestrant may work better for certain sub types of ESR1 gene mutations
neratinib, with or without fulvestrant, could be a useful treatment for people with HER2 gene mutations
capivasertib and fulvestrant may be a useful treatment for people who have oestrogen receptor (ER) positive cancer and AKT1 gene mutations
capivasertib alone may not be a useful treatment for people with PTEN gene mutations
capivasertib alone seemed to work better for people with certain AKT1 gene mutations

We plan to update this page as the research team produce more results, including results for group E.

Hospital visits

If a mutation is found in your blood sample you will be asked to see a doctor and have some tests before you can join one of the treatment groups. These include:

a physical examination
blood tests
heart trace (ECG)
heart scan (echocardiogram) or MUGA scan
bone scan
CT scan

If you join a treatment group, you have a CT scan or MRI scan every 8 weeks for 8 months and then every 12 weeks after that.

You see the trial team regularly while you are having treatment. How often you see them depends on the treatment group you are in. The trial team can tell you more about this.

When you finish treatment, you see the trial team every 6 months for up to 2 years.

Side effects

The most common side effects of fulvestrant include:

discomfort or pain at the injection site
pain affecting the bones, joints and muscles including back pain and pain in the hands and feet
feeling or being sick
skin rash
changes in liver enzymes
hot flushes
hypersensitivity or allergic reactions
weakness or lack of energy and strength

Neratinib is a new drug so there might be side effects we don’t know about yet. So far, the most common side effects of neratinib include:

diarrhoea
feeling or being sick
sore mouth
tummy (abdominal) pain
muscle spasms
tiredness (fatigue)
skin rash
loss of appetite

Capivasertib is a new drug so there might be side effects we don’t know about yet. So far, the most common side effects include:

diarrhoea
high blood sugar levels
loss of appetite
skin rash
feeling or being sick
dry skin
sore mouth

The most common side effects of olaparib include:

a drop in blood cells causing tiredness and breathlessness
tiredness (fatigue)
weakness or lack of energy
feeling or being sick
diarrhoea
indigestion
headaches
taste changes
dizziness
loss of appetite
cough

Ceralasertib is a new drug so there might be side effects we don’t know about yet. So far, the most common side effects include:

a drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness

The trial team will talk to you about all the possible side effects of the you will be having before you agree to take part. They will monitor you during the time you have treatment and you’ll have a phone number to call if you are worried about anything.

We have more information about fulvestrant and olaparib in our Cancer Drugs section.

Early results

In December 2019 the research team presented some results for this trial at a conference in America.

So far, they have looked at the results for treatment groups A, B, C and D.

They plan to publish more results once the trial has finished and they have analysed all the information.