A trial of lenvatinib and pembrolizumab for liver cancer (LEAP 002)

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 comparing lenvatinib on its own with lenvatinib and pembrolizumab for advanced liver cancer.

Advanced liver cancer is liver cancer that has spread into the near by tissues or to another part of the body.

More about this trial

Lenvatinib is a targeted drug called a cancer growth blocker. Doctors can use lenvatinib to treat advanced liver cancer.

Pembrolizumab is an immunotherapy called a monoclonal antibody (MAB). Pembrolizumab works by stimulating the immune system Open a glossary item to fight cancer cells.

Researchers are always looking to improve treatment. They think that adding pembrolizumab to lenvatinib might be better for people with advanced liver cancer.

To find out if it is better half the people in this trial will have lenvatinib and pembrolizumab. The other half will have lenvatinib and a dummy drug (placebo Open a glossary item ).

The aims of this trial are to find how:

well the combination of lenvatinib and pembrolizumab works
safe this combination is
it affects quality of life
well the body handles this combination

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 hepatocellular liver cancer
have cancer that has spread to the blood vessels, lymph nodes or to another part of the body (BCLC stage C) or you have many areas of cancer in the liver (BLC stage B) that can’t be treated with treatment to 1 area of the body (local treatment) or has continued to get worse after local treatment or can’t have treatment with the aim to cure
are willing to have tests that show your liver is working normally (Child-Pugh class A) within 7 days of starting treatment
have at least 1 area of cancer that can be seen and measured on a scan
have satisfactory blood tests results
are as active as you were before your diagnosis (performance status 0 or 1) within 7 days of starting treatment
are willing to use reliable contraception for a month after stopping lenvatinib or for 3 months after stopping pembrolizumab if you or your partner could become pregnant
are at least 18 years old

Who can’t take part

You cannot join this trial if any of these apply.

Cancer related
You:

have cancer that has spread to the brain or spinal cord
have had local treatment such as chemoembolisation or radio ablation within 4 weeks of starting treatment
have had chemotherapy that reached the whole body including anti VEGF treatment for your advanced liver cancer
have had drugs that work by stimulating or stopping T cells of the immune system
have had bleeding from your cancer in the 2 weeks before starting treatment
have changes to your brain such as how you think, your personality or your memory caused by your cancer within the past 6 months and treatment for it hadn’t worked within 3 days
have cancer that has grown into the large blood vessel of the liver called the portal vein
have cancer that has spread to a major blood vessel called the inferior vena cava
have cancer that is affecting your heart
have fluid in your abdomen (ascites) that the doctor can see or feel and isn’t controlled by medication

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

have had bleeding from the food pipe (oesophagus) or stomach within the last 6 months
have problems with bleeding
have had a blood clot and are being monitored for it or are taking medication such as warfarin
can’t have a scan such as a CT scan or MRI scan
have a problem that affects how well medications are absorbed in your gut (digestive system)
have an abnormal opening between 2 parts of the body or between the inside and outside of the body that is large
have a major bleed from any part of your body in the 2 weeks before starting treatment
have had a major heart problem such as a heart attack, congestive heart failure or unstable angina within a year of starting treatment
have had a stroke within a year of starting treatment
have had major surgery to the liver in the 4 weeks before starting treatment
still have any ongoing side effects or major complications from any major surgery
have had minor surgery in the 7 days before starting treatment
have a wound, ulcer, bone fracture or similar thing that hasn’t healed
have had radiotherapy, apart from to the liver, in the 2 weeks before starting treatment
still have ongoing side effects from radiotherapy or are still taking steroids
have an immune system that isn’t working properly
are taking steroids or any other medication that affects the immune system in the 7 days before starting treatment
have another cancer that is getting worse or has needed treatment in the past 3 years apart from successfully treated non melanoma skin cancer and carcinoma in situ
are very sensitive to the drugs, or any of their ingredients, used in this trial
have an autoimmune disease that has needed active treatment in the past 2 years apart from medication that replaces a substance in the body for example hormone tablets for a thyroid that doesn’t make enough hormones
have inflammation of the lungs (pneumonitis)
have had steroids in the past for inflammation of the lungs
have a test that shows there is a large amount of protein in the urine
have a heart test or scan that shows the heart isn’t working well enough
have an infection that needs treatment that reaches the whole body apart from hepatitis B and hepatitis C
have both hepatitis B and hepatitis C
have HIV
have active tuberculosis (TB)
have had a donor (allogenic) stem cell or bone marrow transplant
have had an organ transplant
have or had an experimental drug or used an experimental device as part of another clinical trial in the past 4 weeks
have any other medical condition or mental health problem that the doctor or trial team think could affect you taking part

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

have had a live vaccine in the past month
are pregnant or breastfeeding

Trial design

This is an international phase 3 trial. The team need 750 people worldwide to join with 30 people form the UK.

This is a randomised trial. Everyone is put into 1 of 2 groups. Neither you nor your doctor can choose which group you are in. The groups are:

lenvatinib and pembrolizumab
lenvatinib and a dummy drug (placebo)

Lenvatinib is a capsule. You take it once a day. Your doctor will tell you how many to take. You take the capsules at home apart from the days you have pembrolizumab or the dummy drug. On these days you take the lenvatinib capsule at the hospital about an hour after pembrolizumab or the dummy drug.

You have pembrolizumab or the dummy drug as a drip into a vein. You have it every 3 weeks. It takes about 30 minutes to have.

You continue to have lenvatinib as long as it is helping and the side effects aren’t too bad. You continue to have pembrolizumab or the dummy drug for up to 2 years as long as it is helping and the side effects aren’t too bad.

You have a card that says you are taking part in this trial. It has information about the trial and contact numbers of the trial team. You should always carry this card.

Samples
You give several blood samples throughout the trial. Researchers will use these to find out what happens to lenvatinib and pembrolizumab in the body when they are taken together. They will also look for substances (biomarkers Open a glossary item ) in the blood that might show how well treatment is working.

You give a poo (stool) sample before starting treatment then:

at 2 different times during treatment
at the end of treatment

Researchers will use this sample to look for substances (biomarkers) that might show:

how well the treatment might work
how well the treatment is working

You don’t have to give this poo sample if you don’t want to. You can still take part in the trial.

Quality of life
You fill in a few questionnaires before starting treatment then

every 3 weeks for 27 weeks then
every 6 weeks for up to a year

The questions ask about:

how you are
what you can do
any side effects you might have

Hospital visits

You see the doctor to have some tests before you start. These tests include:

a physical examination
blood tests
heart trace (ECG )
heart scan (ECHO or MUGA )
a gastro endoscope
CT scan and or an MRI scan

During treatment you see the doctor every 3 weeks for:

a physical examination
blood tests
heart trace
CT scan and or an MRI scan

When you finish treatment you see the doctor for a physical examination and blood tests. You then see the doctor a month and 2 months later:

to see how you are
for a CT scan and or an MRI scan
heart trace
heart scan

Your doctor will then tell you how often they want to see you.

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. 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 that you are on or have been on an immunotherapy.

The most common side effects of pembrolizumab are:

itching
diarrhoea
cough
joint, back or tummy (stomach) pain
rash
high temperature (fever)
loss of skin colour
the thyroid not making enough hormones (hypothyroidism) causing tiredness, weight gain, feeling cold and constipation
low levels of salt in the blood causing tiredness, confusion, headache and muscle cramps

Lenvatinib can cause some serious side effects that can be life threatening and might need urgent medical attention. You need to tell your doctor straight away if you have any of the following side effects.

The most common serious side effects of lenvatinib are:

stroke, mini stroke or bleeding in the brain causing numbness and weakness on one side of the body
blood clot in the legs causing swelling of the lower leg muscle (calf muscle) that is warm and tender or a blood clot in the lungs (pulmonary embolism) that can cause sudden onset of shortness of breath, rapid breathing, tight feeling in the chest or chest pain, cough or coughing up blood, fast heart rate and a blue colour in the lips
heart problems, feeling your own heart beat (palpitations), heart attack or not being able to pump as well (heart failure) causing severe shortness of breath
an abnormal opening between 2 parts of the body or from inside to the outside of the body (fistula) or a hole forming in the bowel (bowel perforation)
bleeding inside the body particularly from the gut that might cause blood in the poo or black, tarry poo
not enough fluid in your body (dehydration) and your kidneys not working
liver damage causing yellowing of the skin or eyes, loss of appetite, tummy pain or high temperature
changes to the way your brain works causing confusion, drowsiness, poor concentration and loss of consciousness

Other common side effects include:

high or low blood pressure
loss of appetite and weight loss
feeling or being sick
constipation or diarrhoea
tummy (abdominal) pain and indigestion
tiredness and feeling weak
dry, sore or inflamed mouth or throat
high levels of protein in the urine and urinary infections
hoarse voice
headache
red, sore, swollen hands and feet (hand foot syndrome)
joint, muscle, arm or leg pain
cough
a drop in blood cells that help with clotting (platelets) causing an increased risk of bruising and bleeding
swollen legs
thyroid not working as well (hypothyroidism)
rash
feeling dizzy
changes to your taste
trouble sleeping
hair loss
low levels of potassium and calcium in the blood

Your doctor or a member of the trial team will talk to you about the side effects of lenvatinib and pembrolizumab before you agree to take part in this trial.