TRAK-ER is a randomised trial of early detection of molecular relapse with circulating tumour DNA tracking and treatment with palbociclib plus fulvestrant, versus standard endocrine therapy in patients with ER positive HER2 negative breast cancer.
This study is for people who have had oestrogen receptor positive and HER2 negative breast cancer (ER+ HER2- breast cancer) who have previously undergone surgery to remove the tumour in the breast. It is only for people who are taking hormone therapy to reduce the risk of the cancer coming back.
We know that most people who have had their cancer removed by surgery will be cured. However, in some people the cancer will return. This is called a recurrence and regrettably it is often not curable. When the recurrence happens, the patient’s treatment is usually changed.
This study will use a new blood test that we think can pick up signs of cancer returning to help work out much more accurately which patients are risk of recurrence. We hope that by picking up signs of future cancer recurrence very early, we can more effectively treat the cancer, and perhaps prevent the recurrence from happening in some people.
How does the blood test work?
Cancers release their DNA (genetic material) into the blood. This is called circulating tumour DNA (ctDNA). These blood tests can pick up tiny amounts of cancer DNA in the blood and can identify a recurrence very early. Previous studies have shown that this ctDNA can be detected several months to years before cancer recurrence can be seen on a scan.
In this study, patients will firstly have their blood tested every three months for three years. This is called the surveillance part of the study. If cancer DNA is detected, then patients will have a scan to look for any signs that the cancer has come back. If no evidence of cancer is seen on the scan then they will be able enter the treatment part of the study.
What is the study treatment?
In the treatment part of the study, patients will receive either:
a) standard hormone therapies or
b) a combination of two drugs called palbociclib and fulvestrant.
Patients will be allocated to receive a) or b) at random. Neither the doctor nor the patient will have control over which of the two groups the patient is in. The trial will look to see if patients treated with palbociclib and fulvestrant are less likely to have a recurrence compared to people receiving standard hormone therapies. Patients having standard hormone therapies can continue to take the hormone therapy they are taking, or switch to a different one that may work better than the one they are taking.
Palbociclib and fulvestrant have been selected as a treatment choice as we know that together they offer a highly effective treatment for this type of breast cancer. Patients having standard hormone therapies can continue to take the hormone therapy they are taking, or switch to a different one.
This way all patients who enter the surveillance part of the study will potentially be able to benefit from entering the surveillance part of study.
Please see our flow charts PDF, situated at the bottom of this page, to better understand the surveillance and treatment parts of the study.
Please see our 'Who can take part?' page to see who can take part in the study.
ctDNA blood tests
To ensure that we can detect ctDNA, we will first have to analyse the changes in the DNA in each patient’s cancer, from a previous sample of the cancer. This will usually be a sample of the patient’s cancer that has been stored after their operation. For a small proportion of patients, we will not be able to find the changes required for the ctDNA testing. These patients will not be able to continue with the study.
To detect ctDNA in the blood about 40ml (8 teaspoons) is required. This will be collected every 3 months for up to 3 years as part of the surveillance part of the study. Samples will be sent to both laboratories at The Royal Marsden, as well as a company called Invitae which will be doing the analysis to detect the ctDNA.
Chief Investigator: Professor Nicholas Turner, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust
Sponsor: The Royal Marsden NHS Foundation Trust
Collaborators: Pfizer, Invitae, AstraZeneca, The Institute of Cancer Research, UNICANCER, Gustave Roussy, Cancer Campus, Grand Paris
Funding: Pfizer, Invitae, Le Cure and The Royal Marsden Cancer Charity
TRAK-ER surveillance and treatment flow charts