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

Cancer type:

Breast cancer

Status:

Open

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:
Cancer Research UK supports this trial.
 

More about this trial

The usual way to find gene changes (mutations Open a glossary item) in breast cancer cells is to look at a tumour sample taken during surgery or a biopsy Open a glossary item.
 
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 at and analyse ctDNA to find these mutations
  • fit treatment to the gene changes they are looking for
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. They have to have treatment targeting this type of breast cancer.
 
There are currently 5 treatment options available within the trial. 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 mutations the researchers are looking at in this trial are not ones that can be passed on to your family.

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.
 
Who can enter
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 Open a glossary item
  • 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 Open a glossary item 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 Open a glossary item) 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 Open a glossary item 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 Open a glossary item 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 Open a glossary item 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 A
You cannot take part in group A if the following apply. You:
  • have a problem with blood clotting and you are having treatment unless it is low dose aspirin, heparin or clopidogrel
  • have had fulvestrant (unless you had it at lower dose than the usual dose) or a similar drug
Group B
You cannot take part in group B if the following apply. You:
  • have had high doses of chemotherapy drugs such as doxorubicin, epirubicin or mitoxantrone in the past
  • have had already had treatment with a HER2 kinase inhibitor such as lapatinib
  • 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
  • have ER positive breast cancer Open a glossary item and you have a problem with blood clotting and you are having treatment unless it is low dose aspirin, heparin or clopidogrel
Group C
You cannot join part C if the following apply. You:
  • have ER negative breast cancer (but you may be able to join Group D)
  • have diabetes that isn’t well controlled
  • have a problem with blood clotting and you are having treatment unless it is low dose aspirin, heparin or clopidogrel
  • have a problem with the function and pumping action of your heart
  • have already had AZD5363 or a similar drug
  • are taking any medication that blocks an enzyme called CYP3A4
Group D
You cannot join group part D if the following apply. You:
  • have diabetes that isn’t well controlled
  • have a problem with the function and pumping action of your heart
  • have already had AZD5363 or a similar drug
  • are taking any medication that blocks an enzyme called CYP3A4
Group E
You cannot join group E if the following apply. 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 Open a glossary item 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 Open a glossary item or acute myeloid leukaemia (AML) Open a glossary item
  • have a problem with your immune system Open a glossary item 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 mutations. If you have one of the mutations, you might be suitable to have treatment as part of this trial. Approximately 130 patients with a suitable mutation will be able to enter a treatment group. In addition, approximately 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.
 
Depending on the mutation they find, or whether you have triple negative breast cancer, you are put into one of the following 5 groups.
 
Please note, group A, group B, group C and group D are closed. Group E is still open for women to join. 
 
In:
  • group A you have a drug called fulvestrant - this is standard treatment for women with oestrogen receptor (ER) positive breast cancer, but in this trial you have it more frequently than usual
  • group B:
     

    • if you have oestrogen receptor (ER) positive Open a glossary item breast cancer, you have drugs called neratinib and fulvestrant
    • if you have oestrogen (ER) negative Open a glossary item breast cancer you have neratinib
       
  • group C you have a drug called AZD5363 and fulvestrant
  • group D you have AZD5363
  • group E you have olaparib and AZD6738 (this group is for women with triple negative breast cancer)

You have treatment in 28 day cycles. You have it for as long as it is helping you and the side effects aren’t too bad. The 1st day of treatment is called cycle 1 day 1.
 
Group A – fulvestrant - Closed to recruitment
Fulvestrant is a type of hormone treatment. It blocks the actions of the hormone oestrogen in the body. You have fulvestrant as 2 injections – 1 into each buttock.
 
To begin with, in cycle 1, you have fulvestrant on:
  • day 1
  • day 8
  • day 15
Then you have it once every 2 weeks (on day 1 and day 15 of the following cycles). 
 
Group B - neratinib and fulvestrant (for ER positive breast cancer) Closed to recruitment 
To begin with, in cycle 1 you have fulvestrant injections on:
  • day 1
  • day 15
Then you have it once every 4 weeks on day 1 of the following treatment cycles.
 
Neratinib is a type of biological therapy Open a glossary item. It is a cancer growth blocker. Neratinib targets the HER2 mutation and stops signals that cancer cells use to divide and grow. Neratinib is a tablet.
 
You take the tablets once a day, every day. The trial team will give you a fresh supply of tablets every 4 weeks on day 1 of the following treatment cycles.
 
Group B – neratinib (for ER negative breast cancer) Closed to recruitment
You take neratinib tablets once a day, every day. The trial team will give you a fresh supply of tablets every 4 weeks.
 
Group C – AZD5363 and fulvestrant - Closed to recruitment 
To begin with in cycle 1 you have fulvestrant injections on:
  • day 1
  • day 15
You then have it once every 4 weeks on day 1 of the following treatment cycles.
 
AZD5363 is a new type of biological therapy. Researchers think it might stop cancer cells growing normally. AZD5363 is a tablet.
 
You take AZD5363 twice a day for 4 days, followed by 3 days with no tablets, every week for 4 weeks. The trial team will give you a fresh supply of tablets every 4 weeks on day 1 of the following treatment cycles.
 
Group D – AZD5363 - Closed to recruitment 
Each week, you take AZD5363 tablets twice a day for 4 days followed by 3 days with no tablets, every week for 4 weeks. The trial team will give you a fresh supply of tablets every 4 weeks.
 
Group E - olaparib and AZD6738 (for women who have triple negative breast cancer) this part is still open for women to join
You take olaparib tablets twice a day, everyday. AZD6738 is a tablet. You take it once a day for the first 7 days of each cycle of treatment. The trial team will give you a fresh supply of tablets every 4 weeks.
 
All groups
You have treatment for as long as it is helping you and the side effects aren’t too bad. When you stop taking trial treatment, your doctor will discuss your treatment options. If more than one mutation was identified in your blood sample you might be suitable to enter one of the other treatment groups in this trial.
 
Samples for research
If you join one of the treatment groups the researchers will ask for samples of your cancer (a biopsy Open a glossary item) that were removed when you had surgery or a previous biopsy 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 previously. They would like to collect 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 Open a glossary item to help work out why treatment might work for some people and not for others. 

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 Open a glossary item) or MUGA scan Open a glossary item
  • 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
AZD5363 is a new drug so there might be side effects we don’t know about yet. So far, the most common side effects of AZD5363 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
AZD6738 is a new drug so there might be side effects we don’t know about yet. So far, the most common side effects of AZD6738 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 drug (or drugs) 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:

Location

Bournemouth
Bristol
Cambridge
Cardiff
Edinburgh
Exeter
Glasgow
Liverpool
London
Manchester
Nottingham
Oxford
Plymouth
Sheffield
Southampton
Truro

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.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Prof Nicholas Turner

Supported by

Cancer Research UK
Stand Up to Cancer
The Institute of Cancer Research
The Royal Marsden NHS Foundation Trust
AstraZeneca
Puma Biotechnology

Other information

This is Cancer Research UK trial number CRUK/15/010.

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

13382

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Caroline took part in a clinical trial for breast cancer

“I had treatment last year and I want to give something back.”

Last reviewed:

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