A trial of nivolumab and TACE or TAE for cancer of the liver (TACE 3)

Cancer type:

Liver cancer

Status:

Open

Phase:

Phase 2/3

This trial is looking at adding nivolumab to TACE or TAE for people with cancer of the liver. It is for people who have a type of liver cancer called hepatocellular carcinoma (HCC).

TACE involves injecting a substance (such as a gel or tiny beads) that carry a chemotherapy drug into blood vessels in the liver.

TAE works by reducing the blood supply to the liver.

More about this trial

There are a number of different treatments for liver cancer. One treatment is called trans arterial chemoembolisation (TACE) or trans arterial embolisation (TAE). 

TACE involves injecting a substance (such as a gel or tiny beads) that carry a chemotherapy drug into blood vessels in the liver. The chemotherapy drug you have in this trial is called doxorubicin. 

The beads block the blood supply to the liver. This prevents the cancer getting oxygen and food that it needs to grow. The beads release chemotherapy which can kill the cancer cells.

TAE works by reducing the blood supply to the liver. It involves injecting a substance (such as a gel or tiny beads) into your blood vessel to block the blood supply to the liver tumour. This stops the cancer getting the oxygen and nutrients it needs to survive.  

Doctors are trying to improve treatment. In this trial they are looking at a drug called nivolumab. It is a type of immunotherapy. It helps your immune system Open a glossary item find and kill cancer cells. It works by blocking a protein called PD-1 on the surface of certain immune cells called T cells Open a glossary item. Blocking this protein activates the T cells to find and kill cancer cells.

Researchers think that nivolumab might improve treatment. But they aren’t sure so want to find out more. In this trial some people have TACE or TAE and nivolumab. And some have TACE or TAE on its own. 

The aims of this trial are to find out:

  • if nivolumab and TACE or TAE works better than TACE or TAE on its own
  • more about the side effects of the combination 
  • how treatment affects quality of life Open a glossary item

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 type of liver cancer called hepatocellular carcinoma (HCC)
  • You have at least one area of cancer that can be measured on a CT scan Open a glossary item or MRI scan Open a glossary item.
  • You aren’t suitable to have surgery to remove the cancer or to have a liver transplant. 
  • Your liver is working normally (Child-Pugh A).
  • You have a satisfactory score on a scoring system which shows whether you can cope with TACE (HAP score A, B or C).
  • You have satisfactory blood test results. 
  • You are willing to have a new sample of tissue (biopsy Open a glossary item) taken before starting treatment if necessary.
  • You are willing to use reliable contraception for at least 5 months after treatment if you are a woman or for 7 months if you are a man and there is any chance you or your partner could become pregnant. 
  • You are well enough to carry out all your normal activities but might not be able to do heavy physical work (performance status of 0 or 1).
  • You are at least 16 years old. 

Who can’t take part
You cannot join this trial if any of these apply. 

Cancer related
You:

  • have liver cancer that has spread outside of the liver  
  • have already had embolisation or radiotherapy for HCC
  • can’t have liver embolisation for any reason, for example you have a shunt in the liver, abnormal blood flow in the liver or severe problems with the arteries in the liver 
  • have mild, moderate or severe liver damage (Child-Pugh B or C)
  • have a score that shows you won’t cope with chemoembolisation (HAP score D)
  • can’t have treatment with a type of immunotherapy such as nivolumab that targets PD-1
  • have had another cancer apart from those treated successfully with surgery, non melanoma skin cancer Open a glossary item or CIS Open a glossary item of the cervix 
  • have had an experimental treatment  

Medical conditions
You:

  • aren’t as alert as usual due to liver failure, for example you are more drowsy or confused or you have difficulty thinking 
  • have had a bleed in your stomach or food pipe (oesophagus) in the 4 weeks before joining the trial 
  • have a blockage in the main artery or main vein in the liver 
  • have a collection of fluid on the liver and treatment to get rid of it isn’t working 
  • are allergic to the contrast dye Open a glossary item you have for some scans
  • have a condition called interstitial lung disease
  • have a serious infection or an active infection that needs treatment in the 7 days before joining the trial 
  • have had major surgery in the 4 weeks before joining the trial 
  • have hepatitis
  • have symptoms of tuberculosis (TB) or had a test that shows you have TB but aren’t showing symptoms
  • are having treatment to damp down the immune system such as steroids unless it is less than 10mg of prednisolone a day
  • have an inflammatory disease of the gut including Chron’s disease and ulcerative colitis 
  • have an active or suspected autoimmune condition Open a glossary item apart from type 1 diabetes, thyroid problems that are controlled by medications, pale white patches on the skin (vitiligo), hair loss or conditions that won’t come back again 
  • have any other medical condition or mental health problem that means the trial team don’t think you will be suitable to take part in this trial

Other
You:

  • have had a live vaccine Open a glossary item within 30 days before you start trial treatment
  • are allergic to any of the drugs or their ingredients used in the trial
  • are pregnant or breastfeeding

Trial design

This is a phase 2/3 trial. The trial team need 522 people to take part. 

It is a randomised trial. You are part are put into 1 of 2 treatment groups by a computer. Neither you nor your doctor can decide which group you are in. 

You have 1 of the following:

  • TACE or TAE
  • TACE or TAE and nivolumab

TACE or TAE
Your doctor will decide on the most appropriate procedure, either TACE or TAE for your condition.

To have TACE your doctor puts a fine tube (catheter) into your groin. They inject a dye to outline the blood vessels and blood supply of the cancer. The doctor injects a substance (such as a gel or tiny plastic beads) into the small arteries feeding the tumour. This blocks the blood flow to the cancer and slowly releases the chemotherapy. 

You have TAE in the same way. The doctor injects gel or tiny plastic beads into the small arteries which blocks the blood flow to the cancer. 

To have this procedure you have a drug to make you sleepy (sedation). You stay in hospital overnight. 

The team arrange your TACE or TAE appointment and tell you when this takes place. You may have TACE or TAE more than once. Your doctor can tell you more if this applies to you. 

TACE or TAE and nivolumab
You have TACE or TAE in the same way as described above. You have nivolumab as a drip into a vein. This takes an hour each time. 

You have treatment in the following order:

  • nivolumab
  • TACE or TAE about 2 weeks later
  • nivolumab 2 weeks later
  • nivolumab every 4 weeks after that 

You have nivolumab for up to 2 years as long as it is working and the side effects aren’t too bad. You stop treatment if your cancer gets worse. Your doctor will talk to you about other treatment options. 

Follow up
When you finish treatment you see the team every 4 weeks for a check up. 

Samples for research
You have some extra blood samples for research. The trial team hope to use these to learn more about hepatocellular liver cancer. They also ask to have a sample of tissue you had collected when you had a biopsy. 

The team plan to look for biomarkers Open a glossary item. And they might use the samples for other tests in the future.

Quality of life
The trial team ask you to fill out a questionnaire before starting treatment, at set times during the trial and after finishing treatment. The questionnaire asks about any side effects you have had and how you have been feeling. This is called a quality of life study

Hospital visits

You see a doctor to have some tests before you join the trial. These include:

You might also need to have a sample of tissue taken from the liver. 

During treatment you have regular blood tests and check ups with the team. 

You have a CT and if required, an MRI scan:

  • at screening
  • 4 weeks after your first treatment with  TACE or TAE
  • every 12 weeks after that 

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. 
 
Nivolumab can affect the immune system. It may cause inflammation in different parts of the body which can cause serious side effects. They 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 as soon as possible. You should tell them that you are on or have been on an immunotherapy. 

The most common side effects of nivolumab are:

  • diarrhoea or constipation 
  • tiredness (fatigue
  • itchy, dry, red skin or loss of colour (pigment) from areas of skin
  • tummy pain
  • liver or kidney changes
  • high levels of pancreatic enzymes in your blood 
  • an allergic reaction for example you might get a rash, shortness of breath, redness or swelling of the face and dizziness
  • chills
  • cough, sore throat and colds
  • loss of appetite 
  • dizziness or feeling off balance (vertigo)
  • dry mouth
  • fever
  • headache
  • high blood pressure
  • high levels of sugar in the blood
  • inflammation of the gut (colon), mouth or lungs
  • joint pain, stiffness and muscle pain 
  • feeling sick or being sick 
  • shortness of breath
  • changes in the level of a mineral called sodium in the blood
  • swelling, including the face, arms, and legs
  • changes in how the thyroid gland  Open a glossary itemworks
  • tingling, burning, numbness or weakness, possibly in the arms, legs, hands and feet

The side effects of TACE or TAE are:

  • tiredness (fatigue)
  • feeling or being sick 
  • fever
  • tummy (abdomen) pain

We have more information about:

Location

Birmingham
Bournemouth
Bristol
Cambridge
Derriford
Edinburgh
Glasgow
Guildford
Liverpool
London
Manchester
Newcastle upon Tyne
Nottingham
Oxford
Southampton
Sutton
Wirral

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.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Professor Daniel Palmer

Supported by

Bristol-Myers Squibb
Clatterbridge Cancer Centre NHS Foundation Trust

Freephone 0808 800 4040

Last review date

CRUK internal database number:

16023

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Over 60,000 cancer patients enrolled on clinical trials in the UK last year.

Last reviewed:

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