A trial of encorafenib and binimetinib for melanoma that has spread (PREMIUM)

Cancer type:

Melanoma

Secondary cancers

Skin cancer

Status:

Open

Phase:

Phase 2

This trial is looking at 2 drugs called encorafenib and binimetinib before and after surgery for melanoma.

It is for people:

whose melanoma has spread to the lymph nodes or other parts of the body
who can have surgery to completely remove the melanoma
who have melanoma with a change in the BRAF gene

More about this trial

Surgery is a usual treatment for melanoma that has spread to the lymph nodes or other parts of the body. You might also have a targeted cancer drug after surgery. The cancer drug you have depends on how far the cancer has spread. You might have:

a combination of 2 targeted drugs called dabrafenib and trametinib
an immunotherapy such as nivolumab or pembrolizumab

Doctors are looking for ways to improve treatment. In this trial they are looking at a combination of drugs that include encorafenib and binimetinib. This is already a treatment for melanoma that has spread elsewhere in the body and it isn’t possible to have surgery to remove it. Doctors now want to see how well it works for melanoma that the surgeon can completely remove.

We know from research that having encorafenib and binimetinib before surgery might stop the melanoma coming back. Researchers don’t know this for sure, so they are doing this trial to find out more.

In this trial some people have encorafenib and binimetinib before and after surgery. And some people have surgery followed by standard cancer drug treatment. This is the treatment that people have if they don’t take part in a trial.

The main aims of the trial are to find out:

how well encorafenib and binimetinib work to shrink the cancer before surgery
if people are willing to join the trial
if having encorafenib and binimetinib before and after surgery improves treatment
more about any side effects of treatment

The trial team hope to run a larger trial if this one is successful.

Who can enter

The following bullet points are a summary of 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 take part

You may be able to join this trial if all of the following apply. You:

have melanoma that has spread to the lymph nodes (stage 3 melanoma) or other parts of the body (stage 4 melanoma). If you have stage 4 melanoma it has only spread to one other part of the body. And it can be completely removed by surgery.
have cancer that is possible to remove with surgery
have a change (mutation) in the BRAF V600 gene in your melanoma cells
have melanoma that your doctor can measure on a scan and this is the area that the surgeon will remove
have had scans to assess the cancer within 28 days of being put into a treatment group
have a sample of tissue from when you were diagnosed that the trial team can access. The team plan to do some tests on the sample.
can swallow medication
are fully active but might not be able to do heavy physical work (performance status 0 to 1)
have satisfactory blood test results
are willing to use reliable contraception during the trial and for a period after if there is any chance you or your partner could become pregnant
are at least 18 years old

Who can’t take part

Cancer related
You cannot join this trial if any of these apply. You:

have melanoma that didn’t start in the skin
have already had treatment after surgery for melanoma
have had encorafenib, binimetinib, dabrafenib, trametinib or similar drugs in the past
have had radiotherapy to the area of cancer that the surgeon will remove
have had an immunotherapy within 3 months of joining the trial
have melanoma that has spread to the brain or bone
have had another cancer drug within 28 days of joining this trial
have had another cancer within 2 years of joining the trial. And this cancer hasn’t gone away completely or you might need more treatment.
are taking part in another clinical trial that involves a treatment

Medical conditions
You cannot join this trial if any of these apply. You:

have a serious problem with your eyesight
have high blood pressure that isn’t well controlled with medication
have had a heart attack in the last 6 months or have another significant heart problem that needs treatment
have had a stroke in the last 6 months
have a serious condition that affects the muscles such as muscular dystrophy
have an autoimmune condition apart from certain ones. Your doctor will know this.
have HIV, an active hepatitis B or hepatitis C infection or another serious infection
have any other medical condition or mental health problem that the trial team think could affect you taking part

Other
You cannot join this trial if you are pregnant, planning to become pregnant or breastfeeding.

Trial design

This is a phase 2 trial. The trial team need 45 people to take part.

It is a randomised trial. A computer puts you into a treatment group. In this trial, 2 out of every 3 people have encorafenib and binimetinib. And 1 out of every 3 people standard cancer treatment.

There are 2 are groups:

about 30 people have encorafenib and binimetinib before and after surgery
about 15 people have surgery followed by standard cancer treatment. This is the usual treatment.

Encorafenib and binimetinib group
Encorafenib and binimetinib are tablets. You have encorafenib and binimetinib for 8 weeks before surgery. You have treatment in cycles. Each 4 week period is a cycle of treatment Open a glossary item .

You take:

encorafenib once a day, every day
binimetinib twice a day, every day

You then have surgery as planned. This is the same surgery you would have whether you were in the trial or not.

After surgery you have encorafenib and binimetinib for up to 44 weeks. This is as long as it is working and the side effects aren’t too bad. You start it within 12 weeks of surgery. You have it as described above.

You won’t be able to continue to have encorafenib and binimetinib after surgery if the surgeon can’t remove all of the cancer. The trial team will discuss the treatment options with you if this happens.

Standard treatment group
You have your surgery as planned. This is followed by a standard cancer drug. The treatment you have depends on how far the cancer has spread.

You either have:

dabrafenib and trametinib tablets or
nivolumab or pembrolizumab. You have these as a drip into a vein.

You start treatment within 12 weeks of surgery. Your doctor can tell you which treatment you’ll have and how often you have it.

You have this for up to 1 year after surgery as long as treatment is working and the side effects aren’t too bad.

Quality of life
The trial team ask you to fill out some questionnaires:

before you start treatment
at set times during treatment and after treatment

The questionnaires ask about side effects and how you’ve been feeling. This is called a quality of life study.

Blood and tissue samples
The researchers take some extra blood samples. Where possible, you have these at the same time as your routine blood tests. They also need a sample of tissue Open a glossary item that they take from the melanoma during surgery.

They plan to use the samples to:

see how well the treatment is working
look at the make up of the melanoma
look for substances called biomarkers to help work out why treatment might work for some people and not for others

The trial team also ask to take a tissue sample if the cancer gets worse.

Hospital visits

You see a doctor and have some tests before you join the trial. These include:

a physical examination
heart trace (ECG)
heart scan (echo)
blood tests
a check to see if you have swelling in the arms or legs (lymphoedema assessment) if this applies
CT scan, PET-CT scan or an MRI scan

Encorafenib and binimetinib group
You see the trial team once a month before surgery. In week 3, a member of the team will call you to find out if you are having any side effects.

After surgery you see the doctor once a month for a check up. Some of the consultations might be a phone or video call. You’ll still need to go to the hospital at least every 3 months for a check up.

Standard treatment group
Your healthcare team can let you know how often you have treatment at the hospital. This depends on the cancer drugs you are having.

You see the trial doctor at least every 6 weeks. Some of these appointments might be video or phone calls. You still need to go to the hospital at least every 12 weeks for a check up.

Both groups
Everyone in the trial has a CT scan, PET-CT scan or MRI scan every 3 months. You stop the trial scans if your cancer gets worse.

You see the trial team one month after you finish treatment for a check up. After that you see them once every 3 months.

Side effects

The trial team monitor you during treatment and afterwards. Contact your advice line or tell your doctor or nurse if any side effects are bad or not getting better.

The most common side effects of binimetinib in combination with encorafenib include: