
“Deborah agreed to take part in a trial as she was keen to help other cancer patients in the future. "If taking part in a trial means others might be helped then I’m very happy with that."
Please note - this trial is no longer recruiting patients. We hope to add results when they are available.
Cancer Research UK supports this trial.
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:
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.
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:
In December 2019 the research team presented the results so far for this trial. There is more information in the ‘trial design’ section below.
You might be able to join this trial to have your blood sample tested if all of the following apply:
You cannot join this trial if any of these apply. You:
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:
You cannot join one of the treatment groups if any of these apply. You:
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:
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:
Please note, groups A, B, C and D are now closed. Group E is still open for women to join.
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.
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:
The research team also looked at how well certain sub groups of cancer responded to treatment in each group.
The team concluded that:
We plan to update this page as the research team produce more results, including results for group E.
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.
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.
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.
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:
The research team also looked at how well certain sub groups of cancer responded to treatment in each group.
The team concluded that:
We plan to update this page as the research team produce more results, including results for group E.
Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.
Prof Nicholas Turner
Cancer Research UK
Stand Up to Cancer
The Institute of Cancer Research
The Royal Marsden NHS Foundation Trust
AstraZeneca
Puma Biotechnology
This is Cancer Research UK trial number CRUK/15/010.
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
“Deborah agreed to take part in a trial as she was keen to help other cancer patients in the future. "If taking part in a trial means others might be helped then I’m very happy with that."