A study testing a new way of managing fever linked to dabrafenib and trametinib for melanoma skin cancer (COMBI-APlus)

Please note - this trial is no longer recruiting patients. We hope to add results when they are available.

Cancer type:

Melanoma

Skin cancer

Status:

Closed

Phase:

Phase 3

This study is looking at how best to manage fever that the combination of dabrafenib and trametinib can cause.

It is for people whose:

melanoma cells have a change in a gene called BRAF
melanoma has either grown into surrounding tissues or lymph nodes and they have had surgery to remove this

More about this trial

The usual treatment for melanoma that has grown into surrounding tissue is to have surgery to remove it. There are several different treatments you might have afterwards to help prevent the cancer coming back.

For example, you might have a combination of 2 drugs called dabrafenib and trametinib. These are both a type of targeted drug called cancer growth blockers. They work in slightly different ways to stop signals that cancer cells use to divide and grow.

A high temperature (fever) is a common side effect of the combination of dabrafenib and trametinib. Sometimes the fever can be severe. And managing it might involve a hospital stay or stopping treatment.

In this study, researchers want to improve how doctors manage fever. They have developed a new system to do this and want to check how well it works.

The main of aims of this study are to see if the new way of managing fever:

lowers the risk of a hospital admission
reduces how severe the fever is
reduces the number of people who permanently stop treatment because of fever

Who can enter

The following bullet points list the entry conditions for this study. Talk to your doctor or the study 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 study if all of the following apply.

You:

have had surgery to remove melanoma that has grown into surrounding tissues (stage 3 melanoma) within 12 weeks of starting study treatment
have a gene change in the melanoma cells called BRAFV600 with specific subtype
have had a heart scan that shows your heart is working well
can swallow and absorb tablets
have satisfactory blood test results
are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
are willing to use reliable contraception during the study and for up to 16 weeks afterwards if there is any chance you or your partner could become pregnant
are at least 18 years old

Who can’t take part

You cannot join this study if any of these apply.

Cancer related

You:

have melanoma of the eye or mucosal melanoma which is a rare type of melanoma that starts in the moist tissue (mucosa) which lines the mouth, nose, food pipe, anus, vulva and vagina
have melanoma that has spread to another part of the body
have already had treatment after or before surgery such as chemotherapy, a targeted drug , vaccines , experimental drugs or radiotherapy
have had an experimental drug in the last 28 days or it hasn’t cleared your body yet
have had any other cancer in the last 2 years apart from basal cell skin cancer , squamous cell skin cancer , or carcinoma insitu (CIS ) of the cervix that was successfully treated

Medical conditions

You:

have heart problems
have or have had a blockage in a vein in your eye called the retinal vein
have a lung condition called intestinal disease or pneumonitis
have had major surgery in the last 2 weeks
have HIV
have any other medical condition or mental health problem that the study team think would affect you taking part

Other

You:

are sensitive to dabrafenib or trametinib
take medication that affects body substances called CYP enzymes in the liver or herbal medicines
are pregnant or breastfeeding

Trial design

This is a phase 3 study. It is taking place worldwide. The researchers need 600 people to take including 30 from the UK.

Everyone has dabrafenib and trametinib. Dabrafenib is a capsule. Trametinib is a tablet.

You take:

dabrafenib capsules twice a day, everyday
trametinib tablets once a day, everyday

You have treatment for up to 1 year.

Managing a fever

The most common side effect of the combination of dabrafenib and trametinib is a fever. Take your temperature if you are feeling unwell. The study team will ask you to contact them if your temperature is 38°C or above. They will tell you what to do. They will follow the specific guidelines in the trial protocol to bring your temperature down to normal as quickly as possible. This might involve stopping treatment for a short time and taking some medication.

The study team will collect information about fevers, hospital stays and if you had to stop treatment and for how long.

If during the study your melanoma comes back you may have to stop treatment and your doctor will talk to you about other treatment options.

Quality of life

The study team will ask you to fill out a questionnaire before you start treatment and at set times during treatment. The questionnaire will ask about side effects and how you’ve been feeling. This is called a quality of life survey Open a glossary item

Hospital visits

You’ll see a doctor and have some tests before you can take part. These include:

physical examination
eye examination
examination of your skin
blood samples
heart trace (ECG)
heart scan (echocardiogram)
CT scan or MRI scan

You see the study doctor once a month for a check up and blood tests. They’ll give you a fresh supply of tablets at each visit.

During treatment, you have a CT scan at month:

Follow up

The study team follow you up every 3 to 6 months after you complete 12 months of treatment. The total period for treatment and follow up will last for up to 2 years.

After 2 years of follow up the study team will phone you every 3 months to see how you are getting on.

Side effects

The study team will monitor you during the time you have treatment and you’ll have a phone number to call if you are worried about anything.

Please contact the study team straight away if you get a high temperature either the first time or if it gets worse. A high temperature is 38°C or higher on a thermometer.

The study team will tell you what to do about your fever if you develop one.

The most common side effect of the combination of dabrafenib and trametinib are: