A trial looking at pembrolizumab for people with liver cancer (KEYNOTE-937)

Cancer type:

Liver cancer

Status:

Open

Phase:

Phase 3

This trial is for people with cancer that started in the liver (primary liver cancer). It is for people who have had one of the following treatments to remove the cancer:

surgery
heat directly to the tumour (tumour ablation) such as radiofrequency ablation or microwave ablation

More about this trial

The standard treatment for liver cancer that hasn’t spread to a distant part of the body, is surgery or treatment using heat to destroy cancer cells (tumour ablation). There are 2 types of tumour ablation for liver cancer:

radiofrequency ablation (RFA)
microwave ablation (MWA)

But sometimes liver cancer can come back after surgery or tumour ablation. Doctors in this trial, want to find out if a drug called pembrolizumab can help to stop liver cancer from coming back.

Pembrolizumab (Keytruda) is a type of targeted drug called a monoclonal antibody. It targets and blocks the protein PD-1 on the surface of certain immune cells called T-cells. Blocking PD-1 triggers the immune system Open a glossary item to find and kill cancer cells.

Everyone taking part in this trial has surgery or tumour ablation followed by pembrolizumab or a dummy drug (placebo).

The main aim of this trial is to find out how well pembrolizumab works as an adjuvant treatment Open a glossary item for liver cancer.

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 carcinoma (primary liver cancer)
you have had surgery, radiofrequency ablation or microwave ablation to remove the cancer in the past 6 weeks
you have a moderate, high or very high risk of your cancer coming back – your doctor can tell you more about this
you have had a CT scan in the last month and you no longer have signs of cancer
you are willing to give a tissue sample of your cancer taken when you had surgery or a biopsy
you are fully active, more or less as you were before your cancer diagnosis (performance status of 0)
your liver is working normally (Child-Pugh score A)
you have, or have had, liver infection with the hepatitis C virus and you have finished treatment for it more than 4 weeks ago
you have hepatitis B that is controlled
you have satisfactory blood test results
you are at least 18 years old
you are willing to use reliable contraception during treatment and for up to 4 months afterwards if there is any possibility that you or your partner could become pregnant

Who can’t take part

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

have had embolisation or chemoembolisation, hepatic artery infusion or stereotactic body radiotherapy (SBRT)
still have side effects from your previous cancer treatment
have had pembrolizumab or any other similar drug
have had treatment that reached your whole body (systemic) for liver cancer
are currently having any treatment for liver cancer such as radiotherapy, chemotherapy or an investigational treatment
have had another cancer in the past 3 years unless it was non melanoma skin cancer or carcinoma in situ of the cervix and breast that has been successfully treated

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

are taking part in another clinical trial or have taken part in a trial looking at a new drug or device in the last month
have had bleeding from swollen veins in the food pipe or stomach (oesophageal or stomach varices) in the last 6 months
have a build up of fluid in your tummy (ascites)
have problems with your brain (encephalopathy ) caused by the liver disease
have or have had lung problems such as pneumonitis
have an autoimmune disease that needed treatment that reached your whole body in the past 2 years unless it was treatment to replace something that the body makes such as thyroxine or insulin
take or have taken drugs that damp down your immune system such as steroids in the past week unless it was a very small dose
have an active infection that needs antibiotics that reach your whole body
have both active hepatitis B and hepatitis C – your doctor can tell you more about this
have or have had HIV
have active tuberculosis
have any other serious medical condition or mental health problem that the trial team think could affect you taking part
take an amount of drugs or alcohol that is a concern for your doctor

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

are pregnant or breastfeeding
have had a live vaccine in the last month
are sensitive to pembrolizumab or anything it contains

Trial design

This is an international phase 3 trial. Researchers hope that around 950 people worldwide and 27 people from the UK will agree to take part.

It is a randomised trial. Everyone taking part is put into 1 of the following groups by computer:

pembrolizumab
dummy drug

Neither you nor your doctor can choose which treatment you have. And neither you nor your doctor will know which treatment you are having. This is a double blind trial.

keynote-937.png

You have pembrolizumab or dummy drug as a drip into your bloodstream (intravenously). It takes about 30 minutes to have pembrolizumab each time.

You continue to have treatment for as long as it is helping you and the side effects aren’t too bad. You have up to 17 treatments of pembrolizumab, taking about a year in total.

Quality of life
Everybody taking part completes quality of life questionnaires before the start of treatment and:

every 3 weeks during treatment
at the end of treatment
a month after finishing treatment
every 3 months after a year
then every 6 months after 2 years
and then every year until year 5

The questionnaires ask about how you have been feeling and what side effects you have had.

Blood tests
You have extra blood tests as part of this trial. You have them before the start of treatment and then:

every 3 weeks during treatment
at the end of treatment
at set times during your follow up

Researchers want to:

look of certain proteins (biomarkers ) that can help to tell how well the treatment is working
look at the cancer DNA

Tissue sample
The trial team will ask to use a tissue sample of your cancer taken when you had surgery or a biopsy. Researchers want to learn more about how the treatment affects the cancer.

Poo (stool) sample
The trial team might ask you to give a poo sample before the start of treatment and then:

3 weeks after the start of treatment
12 weeks after the start of treatment
at the end of treatment

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

Hospital visits

You see a doctor and have some tests before taking part. These tests might include:

a physical examination
a CT scan or MRI scan
heart trace (ECG )
an endoscopy
blood tests
urine test

During treatment, you see the trial team every 3 weeks. You have blood tests and a physical examination every time you see them. You also have a CT scan or MRI scan every 12 weeks for a year.

When you finish treatment, you see the trial team after a month. You then see the trial team:

every 3 months for 3 years
then every 6 months for 2 years
then every year for 2 years

After 7 years, the trial team will call you every 3 months to check how you are.

Side effects

The trial team monitor you during treatment and afterwards. You have a phone number to call them if you are worried about anything. The team will tell you about all the possible side effects before you start the treatment.

Pembrolizumab affects the immune system. This may cause inflammation in different parts of the body which can cause serious side effects. Side effects can happen during treatment or some months after treatment has finished. Some side effects can be life threatening.

The most common side effects of pembrolizumab are:

skin rashes, itching and changes to your skin colour
loose or watery poo (diarrhoea)
cough
pain in your joints, back and tummy (abdomen)
high temperature (fever)
low levels of thyroid hormones in your body causing tiredness, weight gain and feeling cold
low levels of salts in your body which can cause muscle cramps and feeling sick

We have more information about the possible side effects of pembrolizumab.