A trial of selumetinib for plexiform neurofibromas (KOMET)

Cancer type:

Neurofibroma

Status:

Open

Phase:

Phase 3

This trial is looking at how well selumetinib might work for plexiform neurofibromas.

Plexiform neurofibromas are not cancer but are a benign Open a glossary item growth on the nerves.

This trial is open to people with neurofibromatosis Open a glossary item type 1 (NF1) who have plexiform neurofibromas that are causing symptoms. And you can’t have surgery to remove them.

More about this trial

NF1 is a rare genetic (inherited Open a glossary item ) disease. It can affect many parts of the body including the nervous system. This system is made up of:

the brain and spinal cord, called the central nervous system
the nerves that run throughout the body, called the peripheral nervous system

When NF1 affects the peripheral nervous system this is plexiform neurofibroma (PN).

PN can continue to grow throughout your life. It grows on and along the nerves. This can cause a lot of pain and affect your daily living. PN can also lead to cancer but this is rare.

Doctors treat PN with surgery. However, this is not always possible. Researchers are looking for other treatments for PN.

Selumetinib is a targeted drug Open a glossary item called a growth blocker. It works by stopping an enzyme that PN cells need to grow. Selumetinib is already used to treat some types of cancer.

Researchers think that selumetinib might help people whose PN can’t be removed by surgery. In this trial half the people have selumetinib and the other half have a dummy drug (placebo Open a glossary item ).

The aims of this trial are to find out:

how well selumetinib works for plexiform neurofibroma
more about plexiform neurofibroma
what happens to selumetinib in the body
how the body affects selumetinib
how it affects quality of life

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 neurofibromatosis type 1 (NF1)
have a plexiform neurofibroma (PN) that is causing symptoms. And you can’t have surgery to remove it.
have filled in a pain diary for a certain time. Your doctor can tell you more about this.
have at least 1 area of PN that the doctor can measure and is a certain size. Your doctor knows what size it must be.
have satisfactory blood test results
can look after yourself but might not be able to do heavy physical work (performance status 0 or 1)
are able to swallow capsules whole
are willing to use contraception during the trial and for a certain time after. This is if there is any chance you or your partner could become pregnant.
are at least 18 years old

If you are taking painkilling medication the dose needs to have been the same for the past 28 days before going into the trial.

Who can’t take part

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

might have a malignant glioma or malignant peripheral nerve sheath tumour (MPNST)
had treatment for PN within 4 weeks of starting the trial treatment. For radiotherapy it is 6 weeks.
have ongoing moderate to severe side effects from previous treatment. This is apart from hair thinning, hair lightening or other side effects that your doctor thinks won’t get worse during treatment.
have or had a cancer. This is apart from successfully treated non melanoma skin cancer . You might be able to join if you had a cancer that has been treated with the aim to cure and there has been no sign of it for 5 years or more.
have had a targeted drug called a MEK inhibitor before. Your doctor will know if you have.
are not able to have an MRI scan . This could be because you have a pacemaker, metal in your body for example surgical clips. It could also be because something such as an artificial limb or dental braces is near the tumour.
have a problem with the digestive system that affects how well medication is absorbed into the body
have hepatitis B, hepatitis C or HIV
have an eye problem or a heart problem that could affect you taking part
have high blood pressure that isn’t controlled
have a problem with bleeding
have had a kidney transplant
have moderate to severe liver disease
have major surgery or a major injury within 4 weeks of starting treatment
are taking vitamin E or anything that contains vitamin E. This is unless you are able to stop taking it at least 7 days before starting treatment.
are taking medication that affects the CYP enzymes. This is unless you can stop taking the medication within a certain time before starting treatment. Your doctor will know how long this is.
have taken part in another clinical trial within a certain time before starting treatment. Your doctor will know how long this is.
have any other medical condition or mental health problem that could affect you taking part

Other
You cannot join this trial if any of these apply. You are:

sensitive or allergic to selumetinib or any of its ingredients
pregnant or breastfeeding

Trial design

This is an international phase 3 trial. The team need 146 people worldwide to take part with 10 people in the UK.

It is a randomised double blind trial. A computer puts you into 1 of 2 groups. Neither you nor your doctor can choose which group you go into. And neither you nor your doctor will know which group you are in.

The trial team will be able to tell your doctor which group you are in if this becomes necessary.

The groups are:

people having selumetinib
people having the dummy drug (placebo)

KOMET trial randomisation diagram

Selumetinib is a capsule. You take the capsules twice a day. You must take them on an empty stomach. That means you can’t have any food or drink, apart from water, for 2 hours before taking the capsules and for 1 hour after. Your doctor tells you how many to take.

The dummy drug is a capsule. You take it twice a day. You must take them on an empty stomach. Your doctor tells you how many to take.

You take the dummy drug for a year. After the year you can start taking selumetinib. During the year if your scans show that your PN is getting worse you might be able to start taking selumetinib sooner.

You should not have certain foods and drinks for 7 days before starting treatment and during. As they can affect how well the body absorbs selumetinib. Your doctor will tell more about this.

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

e-Diary
You have an e-diary to fill in before starting treatment and during treatment. You fill it in everyday and record any pain you have from the PN and what painkillers you take. During treatment you will also record when and how much of selumetinib or the dummy drug you take.

There are also questions in the e-diary about:

your general health and wellbeing
what you are able to do
side effects and symptoms

This is a quality of life questionnaire.

You must bring this e-diary with you to every clinic visit.

Optional Interview sub study
A member of the team will phone 3 times during the trial:

before starting treatment (takes about 30 minutes)
a year after starting treatment (takes about an hour)
about 2 years after starting treatment (takes about an hour)

They will arrange to phone you at a time that is convenient to you. The questions are about:

symptoms
how these symptoms affect your daily life
your experiences during the trial

The interviewer records the interview and keeps it in a safe and confidential place.

You don’t have to take part in this sub study.

Samples for research
You give several blood samples and urine samples during the trial. Your doctor will tell when and how often.

Researchers use these samples to find out:

what happens to selumetinib in the body
how selumetinib affects the body
more about plexiform neurofibroma

Hospital visits

You see the doctor for tests before taking part. These include:

a physical examination
blood tests
urine test
heart trace (ECG )
heart scan (ECHO)
eye examination
MRI scan

You see the doctor:

at regular times during treatment
at the end of treatment
a month after stopping treatment

This is to see how you are and to have the same tests you had at the start.

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 selumetinib are: