A trial looking at pembrolizumab and lenvatinib for head and neck cancers (LEAP-010)

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

Cancer type:

Head and neck cancers

Laryngeal cancer

Mouth and oropharyngeal cancer

Nasal and paranasal sinus cancer

Status:

Closed

Phase:

Phase 3

This trial is looking at whether having lenvatinib with pembrolizumab works better than pembrolizumab on its own as a treatment for head and neck cancer.

The trial is open to people who have one of following head and neck cancers:

mouth cancer (oral cancer)
cancer of the back of the mouth (oropharyngeal cancer) caused by the human papilloma virus (HVP)
cancer of the voice box (laryngeal cancer)

More about this trial

Pembrolizumab is an immunotherapy. It works by stimulating your immune system Open a glossary item to help fight cancer. Doctors use pembrolizumab to treat cancer including some head and neck cancers.

Lenvatinib is a targeted drug Open a glossary item called a cancer growth blocker. It works by blocking signals that tell cancer cells to grow. Doctors use lenvatinib to treat some cancers but not head and neck cancers.

Researchers think that pembrolizumab with lenvatinib might work well to treat head and neck cancers. To find this out half the people in the trial have pembrolizumab and lenvatinib. And the other half have pembrolizumab and a dummy drug (placebo Open a glossary item ).

The aims of this trial are to find out:

how safe it is to have pembrolizumab and lenvatinib
how well this combination works
how it affects quality of life

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 you have one of the following head and neck cancers:

mouth cancer (oral cancer)
cancer of the back of the mouth (oropharyngeal cancer) and you have test results that show the human papilloma virus (HVP) caused your cancer
cancer of the voice box (laryngeal cancer)

And all of the following apply:

Your type of cancer is a squamous cell cancer.
You can’t have surgery or radiotherapy with the aim to cure your cancer. If your cancer is newly diagnosed it must have spread from where it started (advanced cancer) and to at least 1 other area of the body.
Your doctor can see and measure your cancer on a scan.
The trial can get a sample of cancer tissue from when you were diagnosed or if this isn’t available you are willing to have a new sample (biopsy ) done.
Your cancer has a large amount of the PD-L1 protein.
You are active and able to look after yourself (performance status 0 or 1).
You have satisfactory blood test results.
You are willing to use reliable contraception during treatment and for a certain time after if there is any chance you or your partner could become pregnant.
You are at least 18 years old.

Who can’t take part

You cannot join this trial if any of these apply.

Cancer related
You:

can have surgery or radiotherapy with the aim to cure your cancer
had treatment that reaches your whole body (systemic treatment ) with the aim to cure your cancer and the cancer came back or got worse within 6 months of finishing treatment
have cancer that has grown into the surrounding tissue and you had systemic treatment for it and the last dose was less than 6 months ago
have signs or symptoms that mean your cancer has bled within 6 months of going into a treatment group
have a scan that shows your cancer is growing into a major blood vessel
have cancer that has spread to your brain or spinal cord unless you have had treatment, a scan shows it is stable, there are no signs of it getting worse for 4 weeks and you haven’t needed steroids within the 2 weeks of starting treatment
have had radiotherapy to your head and neck before this includes the lymph nodes around your collar bone
have cancer that has broken through the skin and caused ulcers or wounds on your skin
have had another cancer that has started to get worse. Or you have needed to have treatment for cancer within the past 3 years apart from successfully treated non melanoma skin cancer or a carcinoma in situ.

Medical conditions
You:

have high blood pressure that isn’t controlled within the week before starting on the trial
are allergic to pembrolizumab, lenvatinib or any of their ingredients
have an abnormal opening between 2 parts of your body. Or between the inside of your body to the outside that is causing problems and needs surgery. This opening is called a fistula.
have any problems with absorbing medicines. This might be because of a problem with your stomach or because you have had surgery to your stomach or bowel.
have had a major heart problem in the past year that isn’t controlled by medication. This includes heart failure, heart attack, chest pain (angina) or abnormal heart rhythm.
have had a test that shows our heart doesn’t work well enough
had major surgery within 3 weeks of starting treatment
have problems swallowing capsules or liquid medicines. This includes through a tube that goes down your nose to your stomach (nasogastric tube ). Or a feeding tube that goes straight into your stomach through your abdomen (gastronomy tube) unless it is a certain size.
have had pembrolizumab or lenvatinib before
have had a drug treatment that travels throughout the body (systemic treatment) such as chemotherapy within 4 weeks of starting treatment
have had an experimental drug or used an experimental device as part of a clinical trial within 4 weeks of starting treatment
have had radiotherapy within 2 weeks of starting treatment
still have ongoing side effects from radiotherapy
have an immune system that isn’t working well enough
are taking 10mg or more of steroids within 7 days of starting treatment
are taking medication that affects how well your immune system works, or have taken it within 7 days of starting treatment
had systemic treatment for an autoimmune disease within the past 2 years apart from medication to replace substances in the body for example thyroxine for thyroid problems, insulin for diabetes and steroids for problems with the adrenal glands
have inflammation of your lungs not caused by an infection (pneumonitis) or you had pneumonitis and you took steroids for it
have an active infection that needs systemic treatment
have HIV
have hepatitis B or hepatitis C
have had tuberculosis (TB)
had an organ transplant
had a bone marrow or stem cell transplant from another person (allogeneic transplant )
have any other medical condition or mental health problem that your doctor or the trial team think could affect you taking part

Other
You:

have had a live vaccine within 30 days of starting treatment
are pregnant or breastfeeding

Trial design

This is an international phase 3 trial. The team need 500 people worldwide to join with 28 people from the UK.

This is a double blind randomised trial. You are put into treatment groups. Neither you nor your doctor can choose which group you are in. And neither you nor your doctor knows which group you are in. The treatment groups are:

pembrolizumab and lenvatinib
pembrolizumab and a dummy drug (placebo )

LEAP-010 trial randomisation diagram

You have pembrolizumab as a drip into a vein. You have treatment in cycles Open a glossary item . Each cycle is 3 weeks. You have pembrolizumab on the first day of each treatment cycle.

You have pembrolizumab for 2 years as long as it is working and the side effects aren’t too bad.

After the 2 years you might be able to have another year of pembrolizumab. Your doctor will talk to you about this.

You have lenvatinib or the dummy drug as a capsule. You take the capsule once a day every day.

You have lenvatinib or the dummy drug as long as it is working and the side effects aren’t too bad.

Research Samples
You give extra blood samples during the trial. Researchers use these to look for substances (biomarkers Open a glossary item ) to see how well the treatment is working.

They will also ask for a poo (stool) sample to look for biomarkers. You don’t have to give the poo sample if you don’t want to.

Quality of life questionnaires
You fill in 3 questionnaires:

before each treatment
at the end of treatment then
a month later

The questions ask about:

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

This is a quality of life study.

Hospital visits

You see the doctor to have some tests when you agree to take part. These tests include:

a physical examination
blood tests
urine test
mouth examination
heart trace (ECG )
heart scan (ECHO or MUGA )
CT scan or MRI scan

During treatment you see the doctor regularly for a physical examination and blood tests. At some of these visits you also have a heart trace and a CT scan or MRI scan.

You see the doctor at the end of treatment for:

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

You then see the doctor every 3 months until:

your cancer starts to get worse or
you start another treatment for your cancer or
the end of the trial

The trial team will then contact you about every 3 months to see how you are until:

the end of the study or
you decide to withdraw from the study

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.

You have a card that shows you are taking part in this trial. On the card are the contact details of the trial team. Always carry this card with you. Show it to your GP when you see them or to staff at the emergency department of the hospital if you go there. This is so they can contact the trial team if necessary.

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 common side effects of pembrolizumab include:

itching, rash, loss of skin colour
diarrhoea
a cough
joint pain
back pain
high temperature (fever)
tummy (stomach) pain
less hormones being made by your thyroid gland (hypothyroidism) causing tiredness, weight gain, feeling cold and constipation
low level of salt in your blood causing tiredness, confusion, headaches, muscle cramps and or feeling sick

The common side effects of lenvatinib includes:

bleeding in the brain (stroke or mini stroke) causing numbness and weakness on one side of the body
blood clot in your legs (DVT) causing swelling, a warm feeling and tenderness
blood clot in your lungs (pulmonary embolism) causing shortness of breath, rapid breathing, chest feeling tight, chest pain, cough, coughing up blood, fast heartbeat, blue lips
heart problems including fast heart beat (palpitations), heart attack or your heart not being able to pump very well causing shortness of breath
an abnormal opening (fistula) between parts of the body or to the outside of your body such as between the windpipe and the skin or between the bowel and the gut
bleeding in the gut causing black, tarry poo or blood in the poo
low level of fluid in your body (dehydration)
changes to how your kidneys work causing diarrhoea and feeling or being sick
changes to how your liver works causing yellowing of the skin and eyes (jaundice), tiredness, feeling sick, loss of appetite, tummy (abdominal) pain and fever
changes to how your brain works causing confusion, feeling drowsy, poor concentration and loss of consciousness

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

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