A trial of dabrafenib and trametinib for children and young people with a glioma

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

Cancer type:

Brain (and spinal cord) tumours

Children's cancers

Status:

Closed

Phase:

Phase 2

This trial is for children and young people with a glioma that has a change in the BRAF gene called BRAF V600.

It is open to children and young people who are at least 12 months old and haven’t yet had their 18th birthday. And who have a type of brain tumour called a glioma that is either:

slow growing (low grade)
fast growing (high grade) and continued to get worse during treatment or came back after treatment

We use the term ‘you’ in this summary, but if you are a parent we are referring to your child.

More about this trial

Some gliomas have a change (mutation) in the BRAF gene called BRAF V600. The BRAF gene makes a protein that affects how cancers grow and divide.

Dabrafenib and trametinib are targeted drugs. They work by blocking the action of the BRAF protein so possibly stopping the cancer growing or spreading.

We know that the combination of dabrafenib and trametinib works for other cancers that have the BRAF V600 change. Researchers think it could help children and young people whose glioma has the BRAF V600 change.

In this trial everyone who has a fast growing glioma will have dabrafenib and trametinib.

Everyone who has a slow growing glioma will have either:

dabrafenib and trametinib or
carboplatin and vincristine (standard treatment)

The aims of this trial are to find:

how well dabrafenib and trametinib works for children and young people with a glioma
how dabrafenib and trametinib works in the body of children and young people
out about the side effects of having dabrafenib and trametinib together
out how tasty and acceptable liquid dabrafenib and liquid trametinib is

Who can enter

The following bullet points list 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 a low grade glioma that has got worse following surgery or can’t be removed by surgery and needs treatment or you have a high grade glioma that got worse during treatment or came back after treatment
have a glioma with a change (mutation) in the BRAF V600 gene
have a glioma that can be measured on a scan
might need quite a lot of help to look after yourself (Karnofsky performance status 50 or more) or you can get dressed, lie down for most of the day and take part in quiet play (Lansky performance status 50 or more)
have satisfactory blood test results
are willing to use reliable contraception during treatment and for 6 months after if there is any chance you or your partner could become pregnant
are at least 12 months old and haven’t yet had your 18th birthday

Who can’t take part

You cannot join this trial if any of these apply.

Cancer related

You:

have another cancer
have already had dabrafenib, trametinib or any other drug that works in a similar way
have had another cancer treatment within 3 weeks of starting treatment, if you are taking steroids you must be taking a stable dose or a reducing dose a week before starting treatment
have had radiotherapy to the glioma within 3 months unless a scan shows that the glioma has continued to grow
have had an experimental drug as part of a clinical trial within 3 weeks of starting treatment
have had another cancer that had a gene change (mutation) in the RAS gene or a combination of genes that included the BRAF gene
have ongoing moderate to severe side effects from any previous cancer treatment
have had a stem cell transplant within 3 months of starting treatment
have had graft versus host disease (GVHD)

Medical conditions

You can’t take part if you:

are taking medication including herbal treatments that affect the CYP enzymes
have had a heart attack, unstable angina or heart surgery in the past 6 months
have any other serious heart problem such as congestive heart failure
have a problem with your digestive system that could affect how well you absorb tablets, capsules or liquid medication
have hepatitis B or hepatitis C
have any other medical or mental health condition that your doctor or the trial team think could affect you taking part

Other

You can’t take part if you:

are sensitive or allergic to dabrafenib, trametinib or any of their ingredients
are pregnant or breastfeeding

Trial design

This is a phase 2 trial.

There are 2 groups in this trial. Children and young people who have:

a fast growing (high grade) glioma
a slow growing (low grade) glioma

Fast growing glioma

The trial team need about 40 children and young people to join this group. Everyone will take dabrafenib and trametinib.

Slow growing glioma

The trial team need 102 children and young people to join this group.

This part of the trial is randomised. You are put into 1 of 2 groups by a computer. Neither you or your doctor can choose which group you are in.

dabrafenib and trametinib
carboplatin and vincristine

2 out of every 3 children and young people will be in the dabrafenib and trametinib group.

15821_1.png

Dabrafenib and trametinib

You have dabrafenib as a capsule or a liquid. You take it twice a day. Your doctor will tell you how many capsules or how much liquid to take.

You have trametinib as a tablet or a liquid. You take it twice a day. Your doctor will tell you how many tablets or how much liquid to take.

You continue taking dabrafenib and trametinib as long as it is helping and the side effects aren’t too bad.

Carboplatin and vincristine

You have carboplatin and vincristine as a drip into a vein. You have treatment:

once a week for 10 weeks
followed by no treatment for 2 weeks
followed by maintenance treatment

You have maintenance treatment:

once a week for 4 weeks
followed by no treatment for 2 weeks

Each 6 week period is called a cycle of treatment. You have 8 cycles of maintenance treatment.

15821_2.png

After you finish chemotherapy, or if your glioma gets worse, you might be able to start taking dabrafenib and trametinib. Your doctor or a member of the trial team will talk to you about this.

Questionnaires

Children and young people taking dabrafenib and trametinib as a liquid fill in a questionnaire during the 1st week and 5th week of treatment. This questionnaire is about the taste of the liquid.

Everyone who has a slow growing (low grade) glioma will fill in a questionnaire:

every month for 3 months
then every 8 weeks for about 9 months
then every 16 weeks while you are having treatment

The questions are about your general health, wellbeing and any side effects you might have. This is a quality of life questionnaire.

Samples

When you agree to join the trial, the team will ask for a small piece of glioma tissue from when you had your surgery. If this isn’t available, you must agree to have a small piece of glioma tissue (biopsy) taken. They use this sample to confirm your glioma has the change (mutation) in the BRAF V600 gene.

During the trial if your glioma gets worse and you have surgery to remove it the team will ask for a small piece of the glioma tissue. They will use this to learn:

why the treatment has stopped working
more about how dabrafenib and trametinib works
why dabrafenib and trametinib works better for some people and not others

The trial team will take extra blood samples from those who are taking dabrafenib and trametinib. They will use these to find out what happens to these 2 drugs in the body.

They will also ask for extra blood samples at the start of treatment and if your glioma gets worse. You don’t have to agree to these samples being taken. You can still take part in the trial.

Researchers will use the blood samples to look for substances (biomarkers) in them that could help identify who might benefit from this treatment in the future.

Hospital visits

You see the doctor to have some tests before taking part. These tests include:

a physical examination
blood tests
heart trace (ECG)
CT scan
MRI scan or x-ray of your shin bone or wrist
heart scan (ECHO)
eye examination

During treatment you see the doctor:

every week for 5 weeks
at 2 months
then every 2 months for about 9 months
then every 3 to 4 months until you start a new treatment for your glioma

You have your eyes examined every 4 months.

You have a CT scan:

every 2 months for about 9 months
then every 16 weeks until your glioma starts to grow or you are no longer in the trial

You have an MRI scan or x-ray of your shin bone or wrist at:

16 weeks
48 weeks
then every year until the end of treatment

After you start a new treatment a member of the trial team will phone you to see how you are. They might ask you to have a CT scan every 4 months.

Side effects

Your doctor and nurse will monitor you closely for any side effects. Let your doctor or nurse know as soon as possible if:

you have severe side effects
your side effects aren’t getting any better
your side effects are getting worse

Dabrafenib can cause men to lose the ability to have children (fertility). And this might be permanent. If you have been through puberty you might be able to bank your sperm. This is a way of storing your sperm to be used later in a fertility treatment. Your doctor will be able to tell you more about this.

The most common side effects of taking dabrafenib only or dabrafenib and trametinib together include:

high temperature sometimes with low blood pressure, low amount of fluid in the body (dehydration), dizziness and, or fainting
inflammation of the nose and throat
bleeding
a change to the way the liver works
loss of appetite
dizziness
headache
cough
tummy (abdominal) pain
diarrhoea or constipation
feeling or being sick
weakness
dry and, or itchy skin
pain and stiffness of joints
muscle pain
tiredness
pain in the arms or legs
swelling of the arms and, or legs
high blood pressure
chills
flu like illness

We have information about the side effects of carboplatin and the side effects of vincristine.

Your doctor or a member of the trial team will talk to you about the possible side effects of dabrafenib, trametinib, carboplatin and vincristine before you agree to join the trial.