A trial of TACE, pembrolizumab and lenvatinib for cancer of the liver (LEAP-012)

Cancer type:

Liver cancer

Status:

Open

Phase:

Phase 3

This trial is looking at adding pembrolizumab and lenvatinib to TACE to improve treatment for liver cancer. 

TACE gives high doses of chemotherapy to the tumour in the liver and blocks off the blood supply.

This trial is for people who have:

  • a type of liver cancer called hepatocellular carcinoma (HCC) and
  • whose cancer hasn’t spread elsewhere in the body 

More about this trial

There are a number of different treatments for liver cancer. One treatment is called trans arterial chemoembolisation (TACE). It involves injecting a substance (such as a gel or tiny beads) that carry a chemotherapy drug into blood vessels in the liver. 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.

Doctors are looking for ways to improve treatment for people with hepatocellular liver cancer. In this trial they are looking at adding 2 drugs called pembrolizumab and lenvatinib to TACE. Doctors aren’t sure how well this will work, so they are running this trial to find out more. 

Pembrolizumab is an immunotherapy. It helps your immune system Open a glossary item find and kill cancer cells. 
        
Lenvatinib is a type of targeted drug Open a glossary item called a cancer growth blocker. It stops signals that cancer cells use to divide and grow. It is already a treatment for hepatocellular liver cancer that has spread elsewhere in the body. 

In this trial, some people have TACE, lenvatinib and pembrolizumab. And some have TACE and 2 dummy drugs (placebos Open a glossary item). 

The main aims of the trial are to find out:

  • how safe it is to have pembrolizumab and lenvatinib together with TACE 
  • if adding pembrolizumab and lenvatinib to TACE improves treatment 
  • more about the side effects 
  • how treatment affects quality of life Open a glossary item

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 hepatocellular carcinoma (HCC) that hasn’t spread and you can’t have treatment with the aim to cure. Your doctor will know this. 
  • have at least one area of cancer that your doctor can see on a scan 
  • can have TACE to treat all the areas of cancer in the liver 
  • your liver is working normally (Child-Pugh A)
  • have a satisfactory score on a scoring system which shows whether you can cope with TACE (HAP score A, B or C)
  • have satisfactory blood test results
  • have blood pressure that is well controlled with or without medication 
  • are well enough to carry out all your normal activities but might not be able to do heavy physical work (performance status 0 to 1)
  • are willing to use reliable contraception during the trial and for a period after if there is any chance you or your partner could become pregnant
  • are at least 18 years old 

Who can’t take part

Cancer related
You cannot join this trial if any of these apply. You:

  • have areas of cancer in the liver that measure more than 10cm across, you have more than 10 areas of cancer in the liver or the cancer is in more than half of the liver 
  • have fibrolamellar carcinoma or a mixture of hepatocellular carcinoma and bile duct cancer (cholangiocarcinoma). Your doctor will know this.
  • have developed changes in the brain in the last 6 months that liver disease can cause and the treatment isn’t working. This is called hepatic encephalopathy (HE). 
  • are suitable to have a liver transplant, surgery or treatment using heat to destroy liver cancer (ablation)
  • have cancer that has spread outside of the liver including into the main portal vein. This is a large vein that brings blood from your bowel to the liver. 
  • have had chemotherapy to the whole body (systemic treatment Open a glossary item), drugs that block cancer blood vessel growth or an experimental treatment for HCC liver cancer 
  • have had lenvatinib, pembrolizumab or similar types of drugs in the past
  • have had treatment directly to the liver. You can join if you had ablation or surgery to the liver more than 4 weeks before the first dose of trial treatment. 
  • are having an experimental drug or using a device as part of a clinical trial in the 4 weeks before you start trial treatment 
  • have had another cancer in the past 3 years. You might be able to take part if you have had non melanoma skin cancer Open a glossary item or carcinoma insitu Open a glossary item of the breast or cervix that have been successfully treated. 

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

  • have had bleeding from your food pipe (oesophagus) or stomach in the last 6 months
  • have a bleeding or clotting problem or you are taking warfarin to thin the blood. You can take part if you are having other blood thinners or heparin. Your doctor will know about this.
  • have had a significant bleed within 2 weeks of the first dose of trial treatment 
  • have a build up of fluid in your tummy that your doctor finds during an examination and it isn’t controlled with medication. You might be able to join if you have a collection of the fluid that a routine scan picks up.
  • have any condition that means you can’t absorb lenvatinib 
  • have an opening between 2 parts of the body (fistula) 
  • have had a heart attack or a significant heart problem Open a glossary item that needed treatment within 12 months of the first dose of trial treatment 
  • have had major surgery to the liver within 4 weeks of the first dose of trial treatment or you aren’t better after your surgery 
  • have had minor surgery within a week of the first dose of trial treatment 
  • have a serious non healing wound, ulcer, or bone fracture
  • have a problem with how your immune system Open a glossary item works, you are having long term steroid treatment or you have had treatment that damps down the immune system in the week before starting trial treatment 
  • have an active autoimmune condition Open a glossary item that needed treatment in the last 2 years apart from certain ones
  • had inflammation of the lung tissue (pneumonitis) that needed steroid treatment or you have current pneumonitis 
  • have HIV, tuberculosis or an active infection that needs treatment. You might be able to take part if you have an active hepatitis B or hepatitis C infection. This depends on the treatment and your doctor will check this. 
  • have hepatitis B and hepatitis C at the same time
  • have protein in your urine 
  • have had a transplant with somebody else’s cells (allogeneic transplant Open a glossary item) or you have had an organ transplant Open a glossary item in the past 
  • have any other medical condition or mental health problem that would affect you taking part in the trial 

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

  • have had a live vaccine Open a glossary item within 30 days of the first dose of trial treatment 
  • are allergic to the contrast dye Open a glossary item you have for some scans
  • have a problem with drugs or alcohol 
  • are allergic to pembrolizumab, lenvatinib or anything they contain 

Trial design

This phase 3 trial is taking place worldwide. The team need to find 950 people to take part including 10 people from the UK. 

It is a randomised trial. A computer puts you into a treatment group.  Neither you nor your doctor will be able to decide which group you are in. There are 2 treatment groups. 

You have 1 of the following:

  • TACE, pembrolizumab and lenvatinib 
  • TACE and 2 dummy drugs (placebo Open a glossary item)

Treatment and how you have it 
To have TACE, your doctor threads a catheter through a small cut at the top of your leg (groin). You have an injection of a local anaesthetic to numb this area first. And you might have sedation to make you feel drowsy. The catheter goes into a blood vessel called the femoral artery and up to the artery that supplies blood to the liver. You have chemotherapy through this catheter. There is more information about what happens during TACE treatment.

You have TACE up to 4 times during the trial. You have the first TACE treatment 2 to 4 weeks after you start trial treatment. You have the next TACE treatments at least one month apart. 

Lenvatinib or the dummy drug is a capsule. You take it once a day, every day.  You have treatment for up to 2 years as long as it is working and the side effects aren’t too bad.

You have pembrolizumab or the dummy drug as a drip into a vein. You have it once every 6 weeks. You have treatment for up to 2 years as long as it is working and the side effects aren’t too bad. 

Samples for research 
The researchers might ask you to give an extra tissue sample. They also ask to take some extra blood samples. Where possible, you have these at the same time as your routine blood tests.

They plan to use the samples to:

  • see how well the treatment is working 
  • look at genes Open a glossary item to understand more about liver cancer 
  • look for substances called biomarkers Open a glossary item to help work out why treatment might work for some people and not for others
  • see what happens to treatment in the body 

The team might also ask you to give a poo sample during the trial. You can say no to giving the tissue sample and poo sample. It won’t affect you taking part in the rest of the trial.

Quality of life
The trial team ask you to fill out some questionnaires:

  • before you start treatment
  • at set times during treatment
  • at set times after treatment 

The questionnaires ask about side effects and how you’ve been feeling. This is called a quality of life study.

Hospital visits

You see the doctor and have tests before you can take part. These include:

You have TACE at the hospital. You will need to stay overnight after treatment. Your doctor can tell you more about these hospital visits. 

You also have pembrolizumab or the dummy drug at the hospital on the day care ward. 

During treatment you see the doctor for a check up:

  • once a week for the first 5 weeks and then
  • 1 to 3 times every 3 weeks until you finish treatment 

You have an MRI or CT scan every 9 weeks during treatment. You stop having the trial scans if your cancer gets worse. 

Follow up 
When you finish treatment you see the doctor:

  • at 1 month and then 
  • at 3 months 

The team then follow you up every 3 months. This might be at a routine hospital appointment or they might call you to see how you are getting on. 

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. 

Pembrolizumab can affect the immune system Open a glossary item. This may cause inflammation Open a glossary item and other reactions in different parts of the body. For many people the inflammation and reactions are not too bad. For some people they can cause serious side effects. 

These side effects could happen during treatment or months after treatment has finished. Rarely, these side effects could be life threatening. Your doctor or nurse can explain what these side effects are, the risk of them happening and what to look out for.
 
If you have any of these side effects tell your doctor or nurse as soon as possible. You should tell them that you are on or have been on an immunotherapy.

Having pembrolizumab and lenvatinib together is a new treatment for hepatocellular liver cancer. So there may be side effects we don’t know about yet. Only a few hundred people have had this combination of treatment so far. 

The common side effects of pembrolizumab include:

  • itchy skin or skin rash 
  • loose or watery poo 
  • cough
  • joint, back or tummy pain 
  • high temperatures (fever)
  • loss of skin colour
  • not enough thyroid hormone. You may feel tired, gain weight, feel cold or have constipation. 
  • low levels of salt in the blood. You may feel tired, confused, have a headache, muscle cramps or feel sick.

The most common side effects of lenvatinib include:

  • high or low blood pressure
  • loss of appetite or weight loss
  • feeling or being sick 
  • constipation or diarrhoea
  • tummy (abdominal) pain or indigestion 
  • tiredness (fatigue
  • dry, sore, or inflamed mouth or throat
  • high levels of protein in the urine
  • hoarse voice
  • headache
  • redness, soreness and swelling of the skin on the hands and feet
  • joint, muscle, arm, leg or back pain
  • cough
  • an increased risk of bruising or bleeding 
  • swelling of the legs
  • not enough thyroid hormone, so you may feel tired, feel cold, have dry skin or have hair loss
  • skin rash
  • dizziness
  • odd taste sensation
  • trouble sleeping
  • hair loss
  • urine infections
  • low levels of potassium or calcium in the body 

There are some serious side effects of lenvatinib that could be life threatening. You need to see your doctor or go to the Accident and Emergency (A&E) department at your local hospital if you have any of the signs of these side effects. They include:

  • bleeding into the brain causing weakness or numbness on one side of the body
  • a blood clot in the leg causing swelling of the calf that is warm and tender 
  • a blood clot in the lung causing shortness of breath, rapid breathing, pain or tightening of the chest, cough or coughing up blood, rapid heartbeat and blue tinge to the lips
  • heart problems Open a glossary item, heart palpitations or a heart attack 
  • an abnormal opening between two parts or organs of the body (a fistula) or a hole in the wall. This can cause severe abdominal pain.
  • bleeding inside the body, mainly the gut, causing black, tarry or bloody poo. 
  • severe loss of water from the body (dehydration) and kidney failure. Diarrhoea and being sick a lot can cause this. 
  • a decreased ability of the heart to pump causing severe shortness of breath
  • liver problems or failure. This can cause yellowing of the skin or eyes (jaundice), tiredness, feeling sick, loss of appetite, abdominal pain or high temperature.
  • swelling of the brain causing confusion, drowsiness, poor concentration or loss of consciousness

The trial doctor will talk to you about all the side effects of treatment. You will have a chance to ask any questions you may have. 

We have more information about the following treatments and their side effects:

Location

London

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

Dr Naureen Starling

Supported by

Merck, Sharp & Dohme

If you have questions about the trial please contact our cancer information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

18741

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

Last reviewed:

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