"I was delighted to take part in a clinical trial as it has the potential to really help others in the future.”
A trial looking at improving treatment and outcome for children with liver cancer (PHITT)
The trial is looking at the treatment for 2 types of liver cancer called hepatoblastoma (HB) and hepatocellular carcinoma (HCC).
More about this trial
It is for children and young adults up to the age of 30. We use the term ‘you’ in this summary, but of course if you are a parent, we are referring to your child.
Doctors usually treat children and young adults who have liver cancer with surgery and chemotherapy. Most children who have liver cancer survive after treatment.
Doctors hope that treating children with less chemotherapy can reduce side effects but still cure the cancer. They also hope to improve how long people live for. For children with advanced liver cancer, they hope to treat them with new chemotherapy drugs to improve the outcome of the treatment.
The trial team will be putting people into different treatment groups depending on how far their disease has spread.
For hepatoblastoma (HB) liver cancer you are put into 1 of 4 treatment groups. For hepatocellular carcinoma (HCC) you are put into 1 of 2 treatment groups.
At the same time, they will also be looking at:
- how doctors stage liver cancer
- how liver cancer develops
- how to develop better ways to diagnose liver cancer
- the best way to perform surgery
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.
The trial is split into 2 parts and the trial entry criteria is different for each part.
Part 1 - registration
Who can take part
You may be able to join part 1 of this trial if all of the following apply.
- have been diagnosed with hepatoblastoma (HB) or hepatocellular carcinoma (HCC)
- are 30 years old or younger
- are willing to use reliable contraception during treatment and for six months afterwards if there is any chance that you or your partner could become pregnant
Who can’t take part
You cannot join this trial if any of these apply.
- have had previous chemotherapy
- are currently having chemotherapy, biological therapy or hormone therapy
- have cancer that has come back
- have had an organ transplant, not including a liver transplant
- have an uncontrolled infection
- cannot take part in this trial for any reason
- have another cancer
- are pregnant or breastfeeding
Part 2 – the treatment part of the trial
Those who fulfil all the above entry conditions for part 1, might be suitable to have treatment if all of the following apply.
- are well enough to take part (Lansky score of at least 50) if you are under 16 years old
- are well enough to take part (Karnofsky score of at least 50) if you are 16 years or older
- are not pregnant
- are willing to use reliable contraception during treatment and for 6 months afterwards if there is any chance that you or your partner could become pregnant
There may be other reasons as to why people cannot take part. Your doctor will talk to you about this.
This is a phase 3 trial which is taking place worldwide. Researchers hope that around 300 children and young adults up to the age of 30 will take part. This includes 100 children and young adults from the UK.
It is in 2 parts. When you agree to take part in this trial it means that you agree for the trial team to:
- take extra blood and tumour samples so that researchers can look into your liver cancer
- allow experts to look at your scans and surgery information so they can improve the outcome of your cancer
- collect information about how well you are doing for at least two years
Part 1 (trial registration)
In this part of the trial, the researchers want to work out whether you can take part in part 2 of the trial and which treatment group you should go into.
First, they will confirm your diagnosis with either surgery to remove the tumour or by taking a sample of the cancer tissue (biopsy). This isn’t extra surgery, but the researchers would like to do some extra tests on the sample.
If you have already had surgery, then you will not need to have more surgery but the trial team will ask if they can analyse some of the tissue that was removed during your operation.
You will also have a blood test. Again, this is so they can do some extra tests to understand the cancer better.
They use the results of these tests to decide on which treatment group you should be in.
It might be that some people don’t need further treatment after surgery. If this is the case for you, then you can still take part in the trial. The researchers will want to collect samples from you for at least 2 years.
Part 2 (trial treatment)
You will meet with your doctor who will decide what treatment is best for you. There are 6 treatment groups in the trial and you will be in one of these.
For hepatoblastoma (HB) liver cancer you may take part in 1 of the 4 following treatment groups.
- group A – it is possible to remove the cancer, and it has a low risk of coming back
- group B – you need chemotherapy to shrink the cancer before the doctor can remove it
- group C – your cancer has grown into surrounding tissues and you need chemotherapy before and after surgery
- group D – your cancer has spread elsewhere in the body
For hepatocellular carcinoma (HCC) liver cancer, you are put into 1 of 2 treatment groups. They are:
- group E – it is possible to remove the cancer
- group F – it isn’t possible to remove the cancer
This group is for people who can have an operation to remove the tumour and there is a low risk of the cancer coming back. The researchers want to look at the cancer in the lab and depending on how it looks, decide whether you need to have chemotherapy or not.
Those that don’t need chemotherapy have no further treatment at this stage. Those that do need it will have the chemotherapy drug cisplatin on day 1 of each treatment cycle. You then have no treatment between day 2 and day 21. Each cycle lasts for 3 weeks and you have 2 cycles of treatment, a total of 6 weeks.
This group is for people who need to have chemotherapy before surgery to reduce the size of the tumour. In this part of the trial the researchers want to find out if having 4 cycles of chemotherapy works as well as 6 cycles.
You have the chemotherapy drug cisplatin on day 1 of each treatment cycle. And then have no treatment on day 2 to 14. Then you start the next cycle.
After you have had 2 treatment cycles of cisplatin, you have a CT scan or MRI scan. This is to see how well the treatment is working. The treatment you have next, depends on the result of the scans and if you can have surgery to remove the cancer.
You have another 2 or 4 treatment cycles of cisplatin if doctors think your liver cancer can be removed by surgery. This is chosen at random. Neither you nor your doctor can decide which treatment group you are in.
If your doctors don’t think your liver cancer can be removed by surgery you have another 2 treatment cycles of cisplatin. After this, your doctor will check again if you can have surgery.
If you can have surgery, you have another 2 treatment cycles of cisplatin
If you can’t have surgery, your doctors will decide what further treatment is best for you.
You may have up to 6 cycles of cisplatin.
People taking part in group C need to have chemotherapy before and after surgery. In this part of the trial the researchers want to compare 3 different combinations of chemotherapy to find out which works best.
You are put into 1 of 3 groups at random. So you have 1 of the following:
- SIOPEL-3HR (cisplatin, doxorubicin and carboplatin) - treatment lasts for 20 weeks
- C5VD (cisplatin, doxorubicin, 5FU and vincristine) – treatment lasts for 18 weeks
- intensified cisplatin CDDP-M - treatment lasts for 12 weeks
Your doctor will let you know what treatment you have and how often you have it.
You will have regular scans during treatment. When the doctors think your cancer has shrunk enough, you will have surgery to remove the cancer.
This group is for people whose liver cancer has spread to other parts of the body. Normal treatment is to have chemotherapy and then if possible to have surgery to remove the tumour in the liver and the secondary cancers. You then have more chemotherapy.
This part of the trial is looking at two treatments for people who still can’t have surgery after the chemotherapy.
To begin with, you have standard chemotherapy before surgery. This includes the drugs cisplatin and doxorubicin chemotherapy. This treatment lasts for 10 weeks. You then have a scan to find out if surgery is possible.
You have surgery to remove the cancer in your liver or you have a liver transplant, if the cancer spread has cleared. You then have more chemotherapy with carboplatin and doxorubicin. This lasts for 9 weeks. This is standard treatment if there are no more signs of cancer spread.
If there are still signs of cancer spread, you are put into 1 of 2 treatment groups at random. You have 1 of the following:
- a treatment cycle of carboplatin and doxorubicin, followed by a treatment cycle of carboplatin and etoposide and so on, for up to 6 cycles
- a treatment cycle of carboplatin and doxorubicin, followed by a treatment cycle of vincristine and irinotecan and so on for up to 6 cycles
This group is for people whose cancer can be removed with surgery, and your doctor wants you to have chemotherapy. They want to find out more about the side effects of treatment.
You have cisplatin and doxorubicin chemotherapy. You have cisplatin on day 1 and doxorubicin on days 1 and 2 of each treatment cycle. Each cycle lasts for 3 weeks. You have 4 cycles in total.
This group is for people with a large tumour that your doctor can’t remove with surgery. In this part of the trial, researchers are comparing 2 different treatments to see which works best.
You are put in treatment groups at random. You have chemotherapy and a targeted cancer drug called sorafenib. It is a tablet.
You have 1 of the following:
- PLADO and sorafenib – you have up to 6 cycles of treatment in total
- PLADO/GEMOX and sorafenib – you have up to 8 cycles of treatment in total
After you have had treatment, your doctor will assess whether surgery is possible.
Everyone taking part gives blood, urine and tissue samples for research. The doctor takes the tissue samples during your surgery. You have blood tests and give urine samples at different times throughout your treatment. Your doctors will try and time this when you would normally be having blood tests.
You see a doctor and have some tests before you start treatment. These include:
- a physical examination
- blood tests
- MRI and CT scan
- heart trace (
- a test to check your hearing (audiogram)
- a pregnancy test if you are a female of child bearing age
For part 2 of the trial when you are having treatment
Your hospital visits will depend on which group you are in for your treatment.
Everyone will have physical examinations and blood tests throughout their treatment. You might also have MRI scans, CT scans and ECG’s.
The trial team will want to collect information from you for at least 2 years after your treatment has finished. You go to your hospital for a follow up visit at least every 3 months. At each visit you may have:
- a physical examination
- blood tests
- MRI and CT scan
- heart trace (ECG) once a year
- a test to check your hearing (audiogram) once a year
The most common side effects of the chemotherapy drugs in this trial include:
- feeling or being sick
- a drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
- hearing problems
- damage to your kidneys and heart
- redness and soreness of hands and feet (palmar-plantar syndrome)
- allergic reactions
- loss of appetite
- skin problems – itches and rashes
- hair loss
- diarrhoea and constipation
- muscle and bone pain
- chest pain
- difficulty breathing
- speech changes
The study doctors will explain all the possible side effects before you join the study.
How to join a clinical trial
Professor Bruce Morland
European Union Innovation Programme Horizon 2020
University of Birmingham