A trial of lenvatinib and pembrolizumab for bowel cancer (LEAP-017)

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

Cancer type:

Bowel (colorectal) cancer
Secondary cancers

Status:

Closed

Phase:

Phase 3

This trial is comparing lenvatinib and pembrolizumab with standard treatment Open a glossary item for bowel cancer that has spread (advanced bowel cancer). 

It is for people whose cancer has spread and continued to grow during treatment. It is also for people whose cancer came back after treatment and surgery to remove it is not possible.  

More about this trial

The treatment for advanced bowel cancer that can’t removed by surgery can be either:

  • radiotherapy or
  • chemotherapy or
  • a targeted drug Open a glossary item

In this trial researchers are using chemotherapy or a targeted drug as the standard treatment. The chemotherapy is TAS-102 (Lonsurf). The targeted drug is regorafenib

Pembrolizumab is an immunotherapy. It works by stimulating the immune system Open a glossary item to fight cancer cells. 

Lenvatinib is a targeted drug called a growth blocker. It works by stopping signals that cancer cells need to divide and grow. It also stops cancer cells from forming new blood vessels which they need to grow. 

Researchers think that the combination of pembrolizumab and lenvatinib might be better than the standard treatment. 

To find this out half the people in this trial will have pembrolizumab and lenvatinib. The other half will have TAS-102 or regorafenib. 

The aims of this trial are to find out: 

  • how well pembrolizumab and lenvatinib work compared with TAS-102 or regorafenib
  • if the combination is acceptable 
  • what the side effects of the combination are
  • how the combination 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 adenocarcinoma bowel cancer that has spread and cannot be removed by surgery (stage 4A, B or C)
  • had previous treatment but your cancer has continued to grow or came back. You might be able to join if you could not tolerate having the standard treatment for bowel cancer.  
  • have an area of cancer that the doctor can see and measure on a scan Open a glossary item
  • have a sample of tissue (biopsy) Open a glossary item taken before that the trial team can access or if not you are willing to have a fresh biopsy taken
  • are fit and active but might not be able to do heavy physical work (performance status 0 or 1)
  • can swallow capsules or have liquid medication through a feeding tube
  • have satisfactory blood test results
  • are willing to use contraception during the trial 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 cancer that has a genetic change called microsatellite instability Open a glossary item and deficient mismatch repair (MSI-H/dMMR). Your doctor will test for this and know the results. 
  • have a scan or x-ray that shows your cancer spread is very close to a major blood vessel or that there is very little blood going into the cancer   
  • are coughing up blood if your cancer spread is in the lung or other cancer spreads are bleeding within 2 weeks of starting treatment
  • have fluid on the lungs, around the heart or around the tummy (abdomen) that needs draining or drugs to control it within 2 weeks of joining the trial
  • have cancer spread to the spinal cord, brain or the tissue surrounding the brain
  • have had radiotherapy within 2 weeks of starting treatment. If it was to control symptoms such as pain (palliative radiotherapy) it is 1 week. You can’t join the study if you still have ongoing side effects from any previous radiotherapy. 
  • had another cancer in the past 3 years that has got worse or needed treatment. This is apart from early cancers Open a glossary item treated with the aim to cure. And successfully treated non melanoma skin cancer Open a glossary item and in situ carcinoma Open a glossary item of the cervix or breast. 
  • have already had treatment with certain checkpoint inhibitors Open a glossary item drugs, certain monoclonal antibodies Open a glossary item or VEGFR inhibitors. Your doctor will know if you have had any of these drugs. 
  • have already had regorafenib or TAS-102
  • have had any cancer treatment within 28 days of going into a trial treatment group (randomisation Open a glossary item
  • have ongoing side effects from any previous treatment. This is apart from mild nerve damage and mild hormone (endocrine Open a glossary item) side effects that need treatment or you are taking hormones to replace what the body makes. 

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

  • have a problem with your digestive system Open a glossary item that affects how well your body absorbs capsules or tablets
  • had a major heart problem Open a glossary item such as a heart attack, unstable chest pain (angina) or congestive heart failure in the past year 
  • had a stroke in the past year
  • have high blood pressure that isn’t controlled with or without medication. If you are taking medication there must no change to the dose within the week of randomisation.
  • had a blood clot in an artery within the past year
  • have a high amount of protein in your urine. Your doctor will test for this. 
  • have a heart scan (ECHO Open a glossary item or MUGA Open a glossary item) that shows your heart isn’t working well enough. Your doctor will arrange these tests and will know what the results are. 
  • have a wound that isn’t healing, an ulcer, a bone fracture or an active infection that needs treatment that reaches the whole body (systemic treatment Open a glossary item)
  • have HIV, hepatitis B or hepatitis C
  • have had major surgery within 3 weeks of starting treatment
  • have had medication that stimulates the immune system Open a glossary item such as G-CSF  Open a glossary itemwithin the 4 weeks before joining the trial. You might be able to join if you are taking regular erythropoietin Open a glossary item and the dose has stayed the same for the 2 months before starting trial treatment. 
  • have an abnormal opening between 2 parts of the body or between the inside of the body and the outside of the body (a fistula) 
  • have taken an experimental drug as part of a clinical trial within 28 days of starting this trial treatment
  • are allergic to any of the drugs used in this trial or any of their ingredients
  • have an active autoimmune disease Open a glossary item that has needed systemic treatment in the past 2 years. This is apart from hormone treatment that replaces what the body would make. 
  • have an immune system that isn’t working well enough
  • are taking medication that damps down the immune system. This is apart from a small daily dose of steroids
  • have inflammation of the lungs or had inflammation of the lungs that was treated with steroids
  • have any other medical condition or mental health problem that might 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 itemwithin 30 days of the start of treatment. Please note that the COVID-19 vaccine is allowed as it isn’t a live vaccine. 
  • are pregnant or breastfeeding
     

Trial design

This is an international phase 3 trial. The team need 434 people worldwide to take part with 22 people from the UK.

It is a randomised trial. There are 2 treatment groups. Neither you nor your doctor can choose which group you are in. The groups are:

  • pembrolizumab and lenvatinib 
  • standard treatment 

The standard treatment is either TAS-102 (Lonsurf) or regorafenib. Which one you have, depends on what your doctor decides or what the hospital uses. 


You have pembrolizumab as a drip into a vein. You have it once every 6 weeks. You have pembrolizumab for about 2 years. 

Lenvatinib is a capsule. You take it once a day every day. If you have difficulty swallowing your doctor will talk about other ways to have lenvatinib. 

Regorafenib is a tablet. You take it once a day every day with food. You take it for 3 weeks. You then have a week of not taking it. This 4 week period is a cycle of treatment Open a glossary item

TAS-102 is a tablet. You take it twice a day every day with food. You take TAS-102 for the first 2 weeks. You take it for 5 days only. You then don’t take it for the next 2 weeks. This is a cycle of treatment. 

You have lenvatinib, regorafenib and TAS-102 for at least 2 years. After this you might be able to continue treatment as long as it is helping and the side effects aren’t too bad. 

While having treatment there are certain foods, drinks and medication you should avoid having. Your doctor will talk to you about this. 

Research samples
You give blood samples before, during and after treatment. As much as possible they will take these at the same time as your routine bloods. 

The team ask for a piece of a tissue sample (biopsy) taken previously. If the is not available you might need to have a fresh biopsy taken. 

Researchers use these samples to look:

  • for substances (biomarkers Open a glossary item)
  • at the genes Open a glossary item and DNA  Open a glossary itemin the cancer cells 

This could tell them more about bowel cancer and how to treat it. 

Quality of life
You fill in a questionnaire:

  • before you start treatment 
  • during treatment
  • after finishing treatment

The questions ask about:

  • your general health
  • what daily activities you can do
  • any side effects or symptoms 

This is a quality of life questionnaire

Hospital visits

You see the doctor to have tests before taking part. These tests include:

  • a physical examination Open a glossary item
  • blood tests
  • heart trace (ECG Open a glossary item)
  • heart scan (ECHO  Open a glossary itemor MUGA Open a glossary item)
  • a sample of cancer tissue (biopsy Open a glossary item) only if a previous biopsy isn’t available for the team to access
  • CT scan or an MRI scan
  • a bone scan if the cancer has spread to the bones

You see the doctor regularly during treatment to see how you are and for blood tests. You have a:

  • scan every 8 weeks
  • heart trace every 12 weeks

You see the doctor within a month after stopping treatment and before you start any further treatment. This is to see how you are. 

You then see the doctor or a member of the trial team will phone every 3 months to see how you are. 

You have a scan every 8 weeks to see whether your cancer is getting better or worse. The trial team may contact you more often if they want more tests done. 

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. This 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 tell your doctor or nurse as soon as possible. You should tell them that you are on or have been on an immunotherapy.

The most common side effects of pembrolizumab include:

  • skin problems such as itching, a rash and loss of skin colour
  • diarrhoea
  • a cough
  • joint, back and stomach pain
  • your thyroid Open a glossary item not making enough hormones signs include feeling tired, weight gain, feeling cold and constipation
  • low amount of salt in the blood causing tiredness, confusion, headaches, muscle cramps and or feeling sick

The most common side effects of lenvatinib include:

  • high or low blood pressure
  • loss of appetite, weight loss and changes to taste
  • feeling or being sick
  • constipation or diarrhoea
  • tummy (abdominal) pain
  • indigestion
  • feeling tired and weak (fatigue)
  • dry, sore or inflamed mouth or throat
  • high amount of protein in the urine
  • hoarse voice
  • soreness, swelling and reddening of the palms of the hand and or soles of the feet (hand foot syndrome)
  • joint, muscle, limb and back pain
  • cough
  • a drop in blood cells causing an increased risk of infection, bruising and bleeding
  • swelling of the legs
  • the thyroid not making enough hormones causing tiredness, weakness, dry skin, hair loss and feeling cold
  • rash 
  • feeling dizzy
  • trouble sleeping
  • hair loss
  • low levels of potassium and calcium in the blood which could affect your heartbeat

There are some serious side effects of lenvatinib that could be life threatening. You need to see your doctor or go to the emergency room at the 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
  • blood clot in the leg causing swelling of the calf that is warm and tender 
  • 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 palpitation or heart attack causing pain or pressure in the chest, pain in the arms, neck, back or jaw, shortness of breath, rapid or irregular heartbeat, coughing, bluish colour to the fingers or lips, feeling very tired
  • an abnormal opening between two parts or organs of the body (a fistula) or a hole in the wall of the gut causing severe abdominal pain
  • bleeding inside the body particularly the gut causing black, tarry or bloody poo 
  • severe loss of water from the body (dehydration) and kidney failure caused by diarrhoea and being sick (vomiting)
  • a decreased ability of heart to pump causing severe shortness of breath
  • liver problems or failure causing 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 

We have more information about pembrolizumab and lenvatinib. And information about regorafenib and TAS-102 (Lonsurf) and their side effects.

Your doctor or a member of the trial team will talk to you about all the side effects of these treatments before you agree to take part. 
 

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

Kai Keen Shiu 

Supported by

Merck Sharp & Dohme Ltd

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

Freephone 0808 800 4040

Last review date

CRUK internal database number:

17601

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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