A study of crizotinib for children and young adults with cancer (CRISP)
Cancer type:
Status:
Phase:
This study is looking at crizotinib by itself and with temsirolimus.
It is open to children and young people whose cancer:
- has come back after treatment
- didn’t respond to treatment
Please note, we use the term ‘you’ in this summary, but of course if you are a parent of a child with cancer, we are referring to your child.
More about this trial
Crizotinib is a 
called a cancer growth blocker. It works by blocking certain chemical messages that tell cancer cells to grow. By blocking these messages it could slow the cancer growth or stop it. Crizotinib is already a treatment for non small cell lung cancer that has certain changes () in the cancer cells.
Temsirolimus is a targeted drug called an . It affects how the protein mTOR works. Cancer cells need this protein to divide and grow. It also stops the cancer from forming new blood vessels. By doing this it stops or slows the cancer’s growth. Temsirolimus is already used for a few cancer types.
Researchers think that crizotinib by itself or in combination with temsirolimus might help some children and young people. But first they need to find the best dose of these treatments. The best dose is the one that helps the most and has the fewest side effects.
In this study people will have one of the following:
- crizotinib by itself
- crizotinib with temsirolimus
There are 3 groups in this study. Your doctor will tell you which group you are in.
The aims of the study are to find:
- the best dose of these treatments
- how these treatments affect the body
- side effects of having these treatments
Who can enter
The following bullet points are a summary of 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 you have one of the following cancers that came back after treatment or treatment had stopped working:
- anaplastic large cell lymphoma (ALCL)
- neuroblastoma
- rhabdomyosarcoma
- lymphoma
- a
solid cancer
You can also join if you have inflammatory myofibroblastic tumour (IMT). If you have this you need to be newly diagnosed and the tumour can’t be removed by surgery.
The following also need to apply.
- Your cancer has certain
gene changes (mutation ). The study team will test a piece of the cancer tissue for this. - You are a child who is up and about but you might not be able to join in active play (Lansky performance status 60 and above).
- You are a young adult who can care for yourself but might need help from time to time (Karnofsky performance status 60 and above).
- You have satisfactory blood test results.
- You have an area of cancer that the doctor can measure. This depends on when you join the study and what cancer you have. Your doctor can tell you about this.
- You are willing to use contraception during treatment and for a period of time after. That is if you are sexually active and there might be a chance that you or your partner could become pregnant.
- You are 1 year old to 21 years old.
Who can’t take part
Cancer related
You cannot join this study if any of these apply. You:
- have a cancer that started in the brain (primary brain tumour) or spinal cord
- have cancer that has spread (secondary cancer) to the brain or spinal cord that has not been treated. This includes cancer spread to the tissue or membranes surrounding the brain and spinal cord.
- have lymphoma in the tissue surrounding the brain and spinal cord. This is if there is more than a certain number of white blood cells in the fluid surrounding the brain and spinal cord. Your doctor will know if this applies to you.
- have
spinal cord compression . This is unless it has been treated, your pain is well controlled, it is stable or you have recovered. - had another cancer within the last 3 years. This is apart from
non melanoma skin cancer , early stage cervical cancer or prostate cancer that is only in the prostate or has been successfully treated. - have had
systemic cancer treatment within 2 weeks of starting treatment. For chemotherapy tablets or capsules, such as cyclophosphamide or etoposide, taken daily or weekly it is within 1 week. - have ongoing moderate to severe side effects from any previous treatment
- have taken an experimental drug as part of another clinical trial within 2 weeks of starting treatment
- have had a stem cell transplant from a donor (
allogeneic transplant ) in the past 3 months - have
graft versus host disease (GvHD). You are taking medication to prevent GvHD.
Medical conditions
You cannot join this study if any of these apply. You:
- have an active infection that isn’t controlled
- have a
heart problem such as a heart attack that could affect you taking part - have a
lung problem such as inflammation of the lungs that could affect you taking part - have a problem with your
digestive system that means your body would not be able to absorb medication well enough. This includes conditions like ulcerative colitis . - are taking medication that affects how well you absorb crizotinib. This includes medicines that affect the CYP3A4 enzyme. Your doctor will know which medications these are.
- have any other medical condition or mental health problem that could affect you taking part
You cannot take part in group 2 of this trial if you have neuroblastoma and bone marrow disease only. Your doctor will know if this applies to you.
Other
You cannot join this study if any of these apply. You:
- are allergic or very sensitive to any of the treatments used or any of their ingredients
- have
a live vaccine within 30 days of starting treatment - are pregnant or breastfeeding
Trial design
The study team ask for a piece of cancer tissue. This can be from a previous sample of tissue () if it is available. If this isn’t available you might need to have a fresh sample taken. Your doctor will tell you if this the case for you.
The study team use this piece of tissue to test for certain changes () in your cancer. You can only take part in the study if your cancer has one or more of these gene changes.
If your cancer doesn’t have any of these gene changes your doctor will talk to you about what your treatment choices are.
This is a European and UK phase 1/2 study. The team need 71 children and young adults to take part.
There are 3 groups in this study.
People with anaplastic large cell lymphoma (ALCL) have crizotinib.
People with neuroblastoma or rhabdomyosarcoma have crizotinib and temsirolimus.
People with a solid cancer, lymphoma or inflammatory myofibroblastic tumour (IMT) have crizotinib.
The team want to find the best dose of crizotinib to give:
- by itself
- in combination with temsirolimus
The best dose is the one with the fewest side effects and helps the most.
To do this the first few people in each group have a small dose of crizotinib. If they don’t have any bad side effects the next few have a higher dose. And so on until they find the best dose of crizotinib to have. This is a dose escalation study.
After finding the best dose for each group. The team want to find out how well the treatment works for each group. This is a dose expansion study.
The team have now found the best dose for each group. This part of the study is completed. They are now into the next stage, the dose expansion study.
Crizotinib is a capsule. You take it twice a day, in the morning and then in the evening (about 12 hours apart). You have it with a glass of water. You can have it either with or without food. You might be able to have crizotinib as a liquid if you are not able to swallow capsules. Your doctor will tell you how much crizotinib to take.
You have temsirolimus as a drip into a vein. You have it once a week.
As long as the side effects aren’t too bad and the treatment is helping, people with:
- ALCL have treatment for up to 2 years
- neuroblastoma or rhabdomyosarcoma have treatment for about 8 months
- a solid cancer, lymphoma or inflammatory myofibroblastic tumour (IMT) have treatment for up to 1 year
Diary
You take home a diary to fill in each day. You write how many crizotinib capsules you had and when. You also write down any side effects that you might have. You must bring this to the hospital with you whenever you go to the clinic or for treatment.
Samples for research
The team take several extra blood samples during the study. Where possible they take these samples when you have your routine blood tests done.
They ask for an extra when you have a routine bone marrow test.
The team will ask for an extra tissue sample during the study. They will tell you more about this. You don’t have to agree to have this tissue sample taken.
Researchers use these samples to find out:
- what happens to these drugs in the body
- how they affect the body
- about substances in the body (
biomarkers ) that might show how well treatment is working
Hospital visits
You see the doctor for tests before taking part. These tests include:
- a
physical examination - blood tests
- CT scan , an MRI scan, MIBG or a PET-CT scan. Your doctor chooses which is the best scan or scans for you.
- bone marrow test
- lumbar puncture
- heart trace (ECG)
- heart scan (ECHO)
- eye test
You see the doctor at regular times during treatment. This is for blood tests and to see how you are.
Everyone has more scans during treatment. For some people you also have another bone marrow test. Your doctor will tell you when you are to have these.
You see the doctor when you finish treatment for the same tests you had at the beginning. They will then tell you how often they want to see you.
Side effects
The study 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 temsirolimus are:
- a drop in blood cell causing tiredness, looking pale and an increased risk of infection, bruising and bleeding
- skin problems such as a rash, dry skin and itching
- feeling or being sick
- build up of fluid in the body causing swelling
- loss of appetite and taste changes
- sore mouth
- diarrhoea or constipation
- high sugar levels in the blood
- tiredness and weakness (fatigue)
- low level of minerals in the blood
- pain in different parts of the body
- changes to how well your kidneys work
- headaches
- high levels of fats such as cholesterol in the blood
- shortness of breath and a cough
- inflammation of the lining of the
digestive system - slow healing of a wound
We have more information about the side effects of crizotinib
Your doctor will talk to you about the possible side effects of the treatments and answer any questions you have before you agree to take part.
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
Cancer Research UK Clinical Trials, Unit Birmingham
The Dutch Childhood Oncology Group-Early Clinical Trial Centre (DCOG-ECTC)
Erasmus University Medical Centre
Cancer Research UK trial number
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
