A trial of targeted drugs and chemotherapy for children and young people with cancer (eSMART)
Cancer type:
Status:
Phase:
This trial is for children, teenagers and young adults whose cancer has come back or treatment has stopped working.
Those taking part need to have had a tissue sample taken of their cancer (
) for the SMPaeds programme. This research looks for certain changes () in the of the cancer cells.
This trial is for children, teenagers and young people up to their 18th birthday. We use the term ‘you’, but of course if you are a parent, we are referring to your child.
Cancer Research UK supports this trial.
More about this trial
Researchers are always looking for new treatments for cancers when the stop working or don’t work.
In this trial they are looking at a few different combinations of treatment. Which treatment you have depends on the changes found in the DNA of the sample of cancer tissue. You have a combination of 1 or more of the following drugs:
- targeted drugs
- immunotherapy
- chemotherapy
Targeted drugs block certain proteins and enzymes which can stop the cancer from growing or causing the cancer to die. These drugs are:
- ribociclib
- AZD1775
- olaparib
- enasidenib
They are also looking at drugs that help your to recognise and kill cancer cells. These are immunotherapy drugs. In this trial they are using lirilumab and nivolumab.
The team are also looking at the chemotherapy drugs:
The aims of this trial are to find:
- the best dose of each treatment combination
- out how well these treatment combinations work
- out more about the side effects
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.
In this trial there are several different treatments that you might be able to have.
This is a list of the general entry conditions for this trial. There are other conditions for each treatment that will apply for you to be able to join or others that might mean you can’t join. Your doctor or the trial team will talk to you about these.
Who can take part
You may be able to join this trial if all of the following apply. You:
- have cancer that has got worse after standard treatment or there is no standard treatment available
- gave a sample of cancer tissue (biopsy) for the SMPaeds programme that looks for certain changes (mutations) in the cells’ DNA
- have an area of cancer that can be seen and measured on a
scan - are 13 years old or older and can care for yourself but may not be able to do your normal activities (Karnofsky performance score of 70 or more) or you are 12 years old or younger and you mightn’t play as energetically and you might spend less time than usual in active play (Lansky performance score of 70 or more)
- have satisfactory blood test results
- have had heart tests that show your heart is working well enough (this is only if your previous treatment could affect the heart)
- can swallow capsules if the drug you have in the trial is a capsule
- are at an age where you are sexually active and you are willing to use reliable contraception during treatment and for up to 7 months after if you or your partner could become pregnant
- are up to 17 years old, if you are 18 years old or older you might be able to join the trial if you were diagnosed with cancer when you were younger and now it has come back, got worse or treatment isn’t working. Or if your cancer is a cancer type most commonly found in children rather than adults.
There are also certain other entry conditions for each treatment arm. Your doctor or the trial team will talk to you about these.
Who can’t take part
You cannot join this trial if any of these apply.
Cancer related
You:
- have cancer spread to the brain or spinal cord that is causing symptoms and you are having treatment to that area or you need increasing doses of steroids. If you are having steroids you must be on the same dose for at least 7 days to join the trial
- have had another cancer treatment within 3 weeks of starting treatment
- have had treatment to kill cells in the
bone marrow followed by a transfusion of your own stem cells (autogenic transplant) within 8 weeks of starting treatment - have had a stem cell transplant with somebody else’s cell (
allogeneic transplant ) within 3 months of starting treatment - are taking medication to treat or prevent graft versus host disease (
GVHD ) after a bone marrow transplant - have had radiotherapy within 3 weeks of starting treatment. Or within 6 weeks for mIBG or radiotherapy to the head or spine.
- have ongoing moderate to severe side effects from previous treatment apart from hair loss, loss of hearing and nerve damage (peripheral neuropathy)
Medical conditions
You cannot join this trial if any of these apply. You:
- have problems with your
digestive system such as ulcerative colitis, feeling or being sick or diarrhoea that could affect you well your gut absorbs medication - have severe heart problems within the past 12 months that aren’t controlled by medication
- have an active hepatitis infection
- have HIV
- have an infection that needs treating
- have had major surgery within 3 weeks of starting treatment
- are taking medication that could affect how your heart beats
- are taking medication that affects the CYP enzymes unless it can be stopped a week before starting treatment and not taken during the trial
Other
You cannot join this trial if any of these apply. You:
- are allergic to the drugs used in this trial or any of their ingredients
- have a
live vaccine within 4 weeks of starting treatment - are pregnant or breastfeeding
There are also other conditions for each treatment arm which might mean you are not be able to join the trial. Your doctor or a trial team member will talk to you about them.
Trial design
This is an international phase 1/2 trial.
There are 5 different treatment arms in this trial. Which treatment arm you are in depends on the changes (mutations) in the DNA of your cancer.
Arm A
In this treatment arm the team are looking at ribociclib, topotecan and temozolomide. The team need up to 50 children and young people to join.
The first few children and young people have a low dose of ribociclib, topotecan and temozolomide. If they don’t have bad side effects the next few have a higher dose. And so on until they find the best dose. This is a dose escalation study.
When the researchers find the best dose they will look at how well it works. This is a dose expansion study. For this they need 26 children and young people.
You have treatment every 4 weeks. Each 4 week period is a .
Ribociclib is a capsule. You take it once a day. You take it from day 6 to day 21 of each treatment cycle. You take the capsules whole with a glass of water. You shouldn’t eat or drink, apart from water, for at least 2 hours before taking ribociclib or for 2 hours after taking it.
Temozolomide is a capsule. You take temozolomide once in the morning. You take it from day 1 to day 5 of the treatment cycle. You take the capsules whole with water before having food or drink.
You have topotecan as a drip into a vein. You have it about an hour after taking temozolomide on day 1 to day 5 of the treatment cycle.
You take the ribociclib capsules and temozolomide capsules at home. Your doctor will tell how many to take and what to do if you miss a dose. You have a diary for ribociclib and temozolomide to write down when you took them and how many. You also write down any side effects you have and any questions you might have.
You can have treatment for a year if it is working and the side effects aren’t too bad.
Arm C
In this treatment arm the team are looking at AZD1775 with carboplatin. This is also a dose escalation study. The team need 32 children and young people to join this treatment arm.
You have treatment every 3 weeks. Each 3 week period is a cycle of treatment.
AZD1775 is a capsule. You take them twice a day about 12 hours apart. You take them from day 1 to day 3 of the treatment cycle. You shouldn’t eat or drink, apart from water, for at least 2 hours before taking AZD1775 or for 2 hours after taking it.
You take AZD1775 at home. Your doctor will tell how many to take and what to do if you miss a dose. You have a diary to write down when you took them and how many. You also write down any side effects you have and any questions you might have.
You have carboplatin as a drip into a vein. You have it once every 3 weeks.
You can have treatment for a year if it is working and the side effects aren’t too bad.
Arm D
In this treatment arm researchers are looking at olaparib and irinotecan. This a dose escalation study. The team need up to 31 children and young people to join.
When the team find the best dose they will do a dose expansion study. They need 25 children and young people to join this study.
You have treatment every 3 weeks. Each 3 week period is a cycle of treatment.
Olaparib is a tablet. You take them twice a day from day 1 to day 10 of each cycle of treatment. You swallow them whole with a light snack such as biscuits or a piece of toast.
You can take olaparib at home. Your doctor will tell how many to take and what to do if you miss a dose. You have a diary to write down when you took them and how many. You also write down any side effects you have and any questions you might have.
You have irinotecan as a drip into a vein. You have it on day 4 to day 8 of each treatment cycle.
You can have treatment for a year if it is helping you and the side effects aren’t too bad.
Arm I
In this treatment arm the team are looking at enasidenib. The team need 10 children and young people to join.
Enasidenib is a tablet. You take it once a day. You shouldn’t eat or drink, apart from water, for at least an hour before taking enasidenib or for at least 2 hours after.
You can take enasidenib at home. Your doctor will tell you how many to take and what to do if you miss a dose. You have a diary to write down when you took them and how many. You also write down any side effects you have and any questions you might have.
You can have treatment for a year if it is working and the side effects aren’t too bad.
Arm J
In this treatment arm researchers are looking at lirilumab and nivolumab. This is a dose escalation and dose expansion study.
For the dose escalation study the team need up to 16 children and young people to join. For the dose expansion study the team need 56 children and young people to join.
You have treatment every 4 weeks. Each 4 week period is a cycle of treatment.
You have nivolumab and lirilumab as a drip into a vein. You have nivolumab on the 1st day and 15th day of the treatment cycle. It takes an hour.
You have lirilumab on the 1st day of the treatment cycle. It takes an hour.
You can have treatment for a year if it is working and the side effects aren’t too bad.
Samples
The team will ask for a small piece of the cancer tissue () taken when you were diagnosed.
You also give several blood samples during the trial. Where possible you give these at the same time as your routine blood samples.
Researchers will use these samples to find out more about your cancer and how to treat it.
They will also use the blood samples to find out what happens to these drugs in the body and how these drugs affect your body.
Hospital visits
You see the doctor to have some tests before starting treatment. These tests include:
- physical examination
- blood tests
- urine test
- CT scan or MRI scan
- heart scan (
ECHO ) - heart trace (
ECG ), apart for those going into treatment Arm I
Depending on your cancer type you might have additional scans such as a:
Children and young people going into treatment Arm I also have a bone marrow test if they have leukaemia.
You see the doctor regularly during treatment. You have the same tests apart from the heart scan (ECHO).
At the end of your treatment you see the doctor for the same tests you had at the start. You have a heart trace and heart scan only if your doctor thinks you need it.
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 ribociclib are:
- a drop in blood cells causing an increased risk of infection, shortness of breath, tiredness, bruising and bleeding
- muscle and bone pain
- difficulty breathing
- changes to how the liver works and liver damage
- tiredness and lack of energy (fatigue)
- feeling or being sick
- loss of appetite
- diarrhoea or constipation
- tummy (abdominal) pain
- inflammation of the gut
- inflamed, sore mouth and mouth ulcers
- changes to how your heart works
We have information on temozolomide and topotecan.
The most common side effects of AZD1775 are:
- a drop in blood cells causing an increased risk of infection, shortness of breath, tiredness, bruising and bleeding
- feeling or being sick
- mouth ulcers
- tiredness and lack of energy (fatigue)
- diarrhoea
- fever, chills and muscle pain
- loss of appetite and weight loss
- an increased level of phosphate in the blood
- hair thinning or loss
- itchiness
- changes to how your heart works
We have information on carboplatin.
We have information on olaparib and irinotecan.
The most common side effects of enasidenib are:
- tiredness and lack of energy (fatigue)
- headaches
- difficulty breathing and a cough
- high temperature (fever)
- feeling or being sick
- diarrhoea or constipation
- taste changes
- a drop in blood cells causing an increased risk of infection, tiredness, shortness of breath, bruising and bleeding
- an increased level of bilirubin in the blood causing yellowing of the white of the eyes and skin (jaundice)
- swelling of the arms, hands, legs and feet
- breakdown of cancer cells (tumour lysis syndrome) that can cause high levels of certain chemicals in your body
Another side effect of enasidenib is a condition called differentiation syndrome that affects the blood cells of those with a blood cancer such as leukaemia. It can happen between 10 days and 5 months after starting enasidenib. This can be life threatening if not treated. Symptoms include:
- fever
- cough
- shortness of breath or difficulty breathing
- fluid build up in the lungs or around the lungs or heart
- swelling
- the liver and kidney not working well
- bone pain
Contact your advice line or doctor straight away if you have a blood cancer and have any of the above symptoms.
Lirilumab and nivolumab can affect the immune system. They may cause inflammation in different parts of the body which can cause serious side effects. These could happen during treatment, or some months after treatment has finished. Rarely, these side effects could be life threatening.
If you have any of these side effects, you should tell the doctor or nurse that you are on or have been on an immunotherapy.
The most common side effects of lirilumab are:
- rash, hives, redness, dry skin and severe itching
- tiredness and lack of energy (fatigue)
- high temperature (fever)
We have information on nivolumab.
Your doctor or a member of the trial team will talk to you about the possible side effects of your treatment before you agree to join the trial.
Location
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.
Chief Investigator
Dr Lynley Marshall
Supported by
Cancer Research UK
Institute Gustave-Roussy
University of Birmingham
Innovative Therapies for Children with Cancer European Consortium (ITCC)
Other information
This is Cancer Research UK trial number CRUK/17/013.
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
