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 .
.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:
- 3
- 6
- 12
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:
- high temperature (fever)
- an increased risk of bleeding
- chills
- liver changes
- high blood pressure
- swelling or pain in the arms or legs
- redness and swelling of the throat and nostrils
- loss of appetite
- headache
- dizziness
- cough
- tummy (abdominal pain)
- constipation or diarrhoea
- feeling or being sick
- tiredness (fatigue) or weakness
- painful, stiff joints or muscle pain
We have more information about dabrafenib.
Recruitment start:
Recruitment end:
How to join a clinical trial
Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.
Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.
Chief Investigator
Dr Pippa Corrie
Supported by
Novartis
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
Last review date
CRUK internal database number:
15681
Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.
