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

Please note - this trial is no longer recruiting patients. We hope to add results when they are available.

Cancer type:

Liver cancer

Status:

Closed

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 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

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 ), 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 or carcinoma insitu 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 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 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 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 ) or you have had an organ transplant 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 within 30 days of the first dose of trial treatment
are allergic to the contrast dye 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 )

18741-randomisation.png

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 to understand more about liver cancer
look for substances called biomarkers 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:

blood tests
urine tests
a physical examination
heart trace (ECG)
heart scan (echocardiogram ) or MUGA scan
endoscopy to examine your throat, stomach, and upper intestinal tract
CT scan
MRI scan

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 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 , 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