The Christie Hospital Nhs Foundation Trust

The goal of this clinical trial is to investigate adaptive therapy in late-stage cutaneous melanoma. The main question it aims to answer are:
If the patient having breaks in their treatment allows the less resistant cells to continue to grow, this would result in a tumour with a lower proportion of resistant cells, making the tumour less resistant to the treatment, an increasing the time it takes for the disease to progress?
Participants will
Receive their allocated treatment regimen until their cancer progresses, they or their doctor withdraw them from the study, or until the study ends, whichever happens first.
Attend fortnightly visits to hospital.
Complete EORTC QLQ-C30 and PRO-CTCAE questionnaires, prior to treatment, every 12 weeks and at the point of cancer progression, to assess quality of life.
Researchers will compare the adaptive therapy participant arm with a standard of care arm to answer the research question described above.

The trial is looking for new and better ways to treat melanoma, an aggressive type of skin cancer. Having surgery to remove the melanoma will cure the majority of patients with early stage disease. However, a small percentage of these patients will go on to develop further disease, which may spread to other places in their body.
Currently, patients who have been cured of melanoma will have appointments in clinic to check that further disease has not developed or returned and some may also receive regular scans.
The trial team has developed a blood test that tells us whether cancer cells are still present or is becoming active after a patient has been 'cured' of melanoma, even if a scan looks normal. The test looks for pieces of DNA in the blood that are known to have come from the cancer, which we call 'circulating tumour DNA', or ctDNA. Patients who have ctDNA in their blood have an extremely high chance of the cancer returning.
By using the blood test that we have developed we think that we can identify patients earlier than normal. We think that some of the treatments that are used when melanoma cancer has spread may benefit patients at this earlier stage.
We want to see if these patients with ctDNA in their blood, who have a higher risk of their cancer returning or spreading, and receive treatment early have a better response to their cancer compared to those patients who receive treatment when their cancer has returned and it can be seen on a scan. This could mean we would be able to offer patients earlier treatment in the future using just a blood test rather than a scan, while also providing reassurance to those patients that do not have ctDNA in their blood that they do not need treatment and their cancer is not returning.

This research is being done because the investigators are looking for new and better ways to treat a type of breast cancer called triple negative breast cancer. This type of breast cancer can be more difficult to treat than other types of breast cancer as it does not respond to drugs such as hormonal therapies. One type of treatment that looks promising is immunotherapy using new drugs called immune checkpoint inhibitors.
Immune checkpoints help to regulate the immune system and can stop the immune system from attacking cancer cells. Immune checkpoint inhibitors block this 'off-switch' and aim to help the immune system control the cancer. These drugs have been very effective in other cancers such as melanoma and are now being tested in breast cancer.
In this study patients will receive an immune checkpoint inhibitor called avelumab. Half the patients on the study will also receive aspirin tablets for approximately 18 days as the investigators wish to compare the effects of avelumab alone versus in combination with aspirin.
Patients will attend hospital approximately five times in order to complete all necessary study assessments. The first visit screens patients for suitability, after which a baseline visit will collect the first of two breast tissue biopsies. At the third visit a single dose of Avelumab will be given via an infusion (a drip in the forearm). Patients will then return approximately two weeks later for a second breast tissue biopsy before having a final follow up visit another two weeks later. Blood and urine samples will be taken at various visits throughout the study to help us learn more about the effects these treatments may have on the immune system and on breast cancer cells.