A trial of pembrolizumab and lenvatinib for liver cancer (PRIMER-1)

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 a type of liver cancer called hepatocellular carcinoma
• are able to have surgery to remove the cancer
• have at least 1 area of cancer that the doctor can measure on a scan
• are willing to have tissue samples (biopsies ) taken
• have a liver that is working normally. Your doctor will check if it is.
• are able to swallow capsules
• have satisfactory blood test results
• are fully active but might not be able to do heavy physical work (performance status 0 or 1)
• are willing to use contraception during treatment and for a time 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 a mixed type of liver cancer or another type that isn’t hepatocellular carcinoma
• have cancer that has spread out of the liver or is in a major blood vessel such as the portal vein
• have had chemotherapy
• have had treatment that stops cancer growing blood vessels (VEGF  treatment). Your doctor will know if you have had this.
• have had treatment to the area of cancer in the liver. This includes chemoembolisation (TACE), radiotherapy and heat to destroy the cancer (RFA or MWA).
• have had an experimental treatment as part of a clinical trial for liver cancer that could not be removed by surgery or that has spread to another part of the body
• have already had an immunotherapy  drug that works by affecting the T cell  receptors on the cancer cells. Your doctor will know if you have.
• are bleeding from the cancer within 2 weeks of starting treatment
• have or had a cancer in the past 3 years that needed treatment or got worse. This is apart from successfully treated non melanoma skin cancer  and carcinoma in situ . 

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

• have had bleeding from the veins in your food pipe (oesophagus) or stomach (gastric) within the past 6 months
• have had an active autoimmune disease  that needed treatment in the past 2 years. This is apart from certain ones such as vitiligo and psoriasis. Your doctor will know what the other ones are.
• have or have had inflammation of the lungs not caused by an infection or have scarring of the lung tissue and needed steroids to treat it
• have fluid around the abdomen (ascites) that the doctor finds when they do a physical examination  that cannot be controlled with medication
• have high blood pressure that isn't controlled. If your blood pressure is controlled with medication there must be no change to the medication within 1 week of randomisation  .
• have been diagnosed with a change to how your brain normally works due to liver damage in the past 6 months
• are not able to have a contrast medium  used for scans
• are not able to have an MRI scan . This could be because you have a pacemaker, metal in your body such as surgical clips or you have a cochlear implant.
• have a problem with your digestive system  that could affect how well the body absorbs medication taken by mouth
• are coughing up blood within the 3 weeks before starting trial treatment
• have a heart problem  such as a heart attack, congestive heart failure or unstable chest pain (angina) within the past year or you have changes to your heartbeat within 6 months of starting treatment. You might be able to join if the heartbeat changes are controlled with medication. 
• have a stroke within 6 months of starting treatment
• have an abnormal heart rhythm seen on a heart trace (ECG ). Your doctor will do an ECG before you join the trial.
• have an immune system  that isn’t working well
• are taking steroids or other medications that damp down the immune system within a week of starting treatment. You might be able to join if you are taking a low dose of steroids. Your doctor will know about this.
• are at risk of having a major bleed or developing blood clots
• are taking medication such as warfarin that thins the blood
• have a large amount of protein in your urine. Your doctor will test a sample of your urine for this.
• have ongoing side effects from previous treatment that might affect you taking part. Your doctor will know about this.
• have major surgery to the liver within 4 weeks of starting treatment
• have ongoing complications from any major surgery
• have a minor surgery procedure such as removal of a lump within 7 days of starting treatment
• have a wound, ulcer or broken bone that is not healed or healing
• have HIV
• have hepatitis B and hepatitis C or hepatitis B and hepatitis D. You might be able to join if you have hepatitis B only or hepatitis C only as long as they are controlled with medication.
• have any other active infection that needs treatment such as antibiotics that reaches the whole body (systemic treatment)
• have a history of active tuberculosis (TB)
• have had a bone marrow transplant or stem cell transplant from a donor (allogenic transplant )
• have had an organ transplant
• have had an experimental drug or used a device as part of a clinical trial within 4 weeks of starting treatment
• have any other medical condition, mental health problem or social situation that could affect you taking part

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

• are allergic or very sensitive to pembrolizumab, lenvatinib or any of their ingredients
• have a live vaccine  within 30 days of joining the trial. The COVID-19 vaccine and some seasonal flu vaccines are not live vaccines. 
• pregnant or breastfeeding