RecruitingPhase IIInterventional

Assessing if stopping and starting standard of care medication for later stage melanoma can reduce the body's resistance to the treatment

Advanced melanoma is a skin cancer that has spread or cannot be removed by surgery. In the UK, patients with a specific gene change in their cancer (a BRAF mutation) usually take two daily targeted medicines: encorafenib and binimetinib. These drugs work well, but the cancer often develops resistance after about a year. This trial, called the DyNAMIc study, tests a strategy known as 'adaptive therapy'. Participants are randomly assigned either to take their tablets continuously as usual, or to take planned breaks. Those taking breaks have a blood test every two weeks to check levels of cancer DNA in their blood. If cancer activity rises, treatment restarts immediately. Researchers hope that giving the body treatment breaks will stop drug-resistant cancer cells from taking over. Taking part involves regular hospital visits, blood tests, and scans to closely monitor your health.

At a glance

Status

Recruiting

Phase

Phase II

Sponsor

The Christie NHS Foundation Trust

Enrolment target

Start

29 Nov 2024

Estimated completion

31 Mar 2027

Cutaneous melanoma

What is this study about?

Melanoma is a type of skin cancer that begins in the cells that give skin its colour. When it reaches an advanced stage, it means the cancer has spread to other parts of the body or cannot be safely removed with surgery. Many people with advanced melanoma have a specific change in their cancer cells called a BRAF mutation. In the UK, the standard treatment for this is a pair of targeted daily drugs called encorafenib and binimetinib, which block the signals that cancer cells need to grow.

While these medicines are often very effective at first, the cancer usually finds a way to resist them after 12 to 15 months. Daily treatment quickly destroys the cancer cells that are easy to kill. However, this leaves behind a small number of resistant cells, which can then multiply without competition. Eventually, the tumour becomes fully resistant, and the treatment stops working.

This study is testing an approach called 'adaptive therapy' to see if it can delay or prevent this resistance. Instead of taking tablets every day without a break, patients on adaptive therapy take planned breaks. Doctors use a sensitive blood test every two weeks to measure tiny fragments of tumour DNA in the blood. If the cancer is quiet, treatment is paused. If the blood test shows the cancer is waking up, treatment restarts straight away.

The idea is that by allowing some treatment-sensitive cells to survive, they keep the drug-resistant cells from taking over completely. Researchers hope this stop-and-start method will keep the cancer under control for much longer than continuous daily treatment, improving long-term outcomes for patients.

Key takeaways

Tests whether taking planned breaks from melanoma medication prevents the cancer from becoming drug-resistant.
Uses a regular blood test every two weeks to carefully track cancer activity and guide treatment pauses.
Compares standard daily treatment against this new stop-and-start approach.
Open to adults with advanced, BRAF-positive skin melanoma.
Participants receive double the usual health monitoring and keep reserve medicine at home.

Who may be eligible?

This trial is for adults aged 18 and over who have advanced skin melanoma that has spread (stage 4) or cannot be removed by surgery (stage 3). To be considered, testing on your tumour must show a specific genetic change known as a BRAF V600 mutation, and a screening blood test must detect measurable levels of tumour DNA.

You will need to be generally well enough to walk around and manage your own daily personal care. Your heart, liver, and kidneys must also be working reasonably well so that the study drugs can be given safely. If you have recently had radiotherapy, it must have finished at least two weeks before joining.

Because the study medicines can cause harm to an unborn child, women who could become pregnant must have a negative pregnancy test before starting. Both men and women taking part must agree to use reliable contraception throughout the study and for a set period after their final dose.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

I am 18 years of age or older.
I have advanced skin melanoma that cannot be surgically removed or has spread.
My cancer has been confirmed to have a BRAF gene mutation.
I am well enough to manage daily personal care and light activities.
I am able to attend hospital appointments every two weeks for blood tests.
I am willing to use reliable contraception if there is any chance of pregnancy.

Answer every question to see your result.

What does participation involve?

If you join the trial, a computer will randomly place you into one of two groups. One group will take the standard tablets every single day, which is the current normal care. The other group will follow adaptive therapy, taking treatment in planned cycles with pauses guided by their blood test results. Neither you nor your doctor can choose your group.

You will visit the hospital every two weeks for blood tests. These tests check your overall health and measure cancer DNA levels to decide whether your treatment should pause or restart. You will also have standard imaging scans, such as CT, PET-CT, or MRI scans, to see how the cancer is responding. At regular intervals, you will fill out questionnaires about how you are feeling and your quality of life.

The study is expected to run for up to three years. You will stay on your assigned treatment for as long as it continues to help you, or until you or your doctor decide it is best to stop. If you are in the stop-start group, you will be given a reserve pack of tablets to keep at home so you can restart treatment without delay whenever your tests show it is needed.

Potential risks and benefits

A key benefit of taking part is receiving twice as much monitoring as standard care, with blood tests every fortnight to catch any changes early. If adaptive therapy proves successful, it could help keep your cancer controlled for longer. However, there is no guarantee that taking breaks will work better than continuous treatment, and pausing medication may cause some anxiety. The study also requires more frequent hospital trips and extra blood draws. Extra scans involve very small amounts of radiation, and some people may experience mild bruising or rare reactions to scan dyes. Taking part is completely voluntary, and you can withdraw at any time without your regular NHS care being affected.

Locations (15)

Addenbrookes
Approximate
Cambridge, England
Guys Hospital
City only
London, England
Royal Preston Hospital
Approximate
Preston, England
Freeman Hospital
Approximate
Newcastle upon Tyne, England
Queens Medical Centre
Approximate
Nottingham, England
John Radcliffe Hospital
Unverified
Oxford, England
Christie Hospital
Unverified
Manchester, England
Clatterbridge Cancer Centre
Unverified
Liverpool, England
Royal Marsden Hospital
Unverified
Surrey, England
Southampton
Unverified
Southampton, England
Velindre Cancer Centre
Unverified
Cardiff, Wales
The Royal Marsden Hospital
Unverified
London, England

Common questions

What is the main difference between the two trial groups?

One group takes their targeted cancer tablets every day as normal. The other group pauses and restarts their medication based on regular blood test results.

What is a ctDNA blood test?

ctDNA stands for circulating tumour DNA. It is a simple blood test that measures tiny pieces of genetic material shed by cancer cells into your blood, showing how active the cancer is.

Will I be left without medication if my cancer starts growing during a break?

No. You will be monitored every two weeks, and you will have a reserve pack of pills at home ready to restart immediately if your blood test shows increased cancer activity.

Do I have to agree to extra tissue biopsies?

No. Any extra biopsies in this trial are entirely optional. You can say no to them and still take part in the main study.

Can I leave the study if I change my mind?

Yes. You can leave the trial at any point, for any reason, and your medical team will move you to the best standard care available.

How to find out more

DyNAMIc Trial Manager

dynamic_study@liverpool.ac.uk - Official trial record

Always speak to your GP or specialist before deciding to take part in a study.