A trial of lenvatinib, pembrolizumab and chemotherapy for non small cell lung cancer (LEAP-006)
Please note - this trial is no longer recruiting patients. We hope to add results when they are available.
Cancer type:
Lung cancer
Non small cell lung cancer
Secondary cancers
Status:
Closed
Phase:
Phase 3
This trial is for people with advanced non small cell lung cancer (NSCLC). Advanced NSCLC can mean one of the following:
- the cancer is in both lungs
- the cancer has spread outside of the lungs into the surrounding area, or elsewhere in the body
- there is a collection of fluid around the lung (pleural effusion) and this fluid contains cancer cells
It is for people who are going to have treatment for advanced NSCLC for the first time.
More about this trial
For advanced NSCLC, you usually have a combination of chemotherapy and targeted drugs. This treatment can help to control the cancer and reduce the symptoms.
Chemotherapy uses anti cancer (cytotoxic) drugs to destroy cancer cells. Common chemotherapy drugs used for advanced NSCLC include:
- platinum chemotherapy such as cisplatin or carboplatin
- pemetrexed (Alimta)
Targeted drugs work by ‘targeting’ differences that a cancer cell has that make them different from normal cells. Pembrolizumab is a type of cancer drug called a monoclonal antibody. It helps the immune system attack the cancer and stop it from growing.
Lenvatinib (Lenvima) is also a targeted drug. It works by blocking certain proteins that help cells to grow new blood vessels. All cancer cells need blood vessels to survive and grow.
Everyone taking part in this trial has 1 of the following:
- pembrolizumab, lenvatinib and chemotherapy (arm 1)
- pembrolizumab, dummy drug and chemotherapy (arm 2)
The chemotherapy treatment includes pemetrexed and either cisplatin or carboplatin. Your doctor can tell you which treatment is best for you.
The main aims of this trial are to:
- find out how well pembrolizumab, lenvatinib and chemotherapy work as a treatment for advanced NSCLC
- learn more about the side effects
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 stage 4A or stage 4B NSCLC
- you have at least 1 area of cancer that can be seen and measured on a scan
- you are willing to have a sample of cancer taken (biopsy) if there isn’t a suitable sample available that doctors can test for a protein called PD-L1
- you are at least 18 years old
- you have satisfactory blood tests results
- your blood pressure is normal and your heart is working well
- you are well enough to carry out your normal activities apart from heavy physical work (performance status of 0 or 1)
- you are willing to use reliable contraception during treatment and for up to 6 months afterwards
Who can’t take part
You cannot join this trial if any of these apply.
Cancer related
- your cancer has receptors for a protein called epidermal growth factor (EGFR positive). Your doctor can tell you more about this
- you have cancer spread in your brain, spinal cord or the membranes surrounding the brain (carcinomatous meningitis) unless you have had treatment, it has been stable for the past month and you have stopped taking steroids more than 2 weeks ago
- your cancer has spread to a major blood vessel and your doctor thinks that you have a high risk of bleeding
- you have had chemotherapy, targeted drugs or any other treatment for advanced NSCLC
- you have had pembrolizumab, lenvatinib or any other similar drug
- you have had radiotherapy in the past 2 weeks and still have moderate or severe side effects from it, or you have had radiotherapy in the past week if it was radiotherapy to help with symptoms (palliative)
- you have had another cancer in the past 3 years unless it was non melanoma skin cancer, a superficial bladder cancer or carcinoma in situ of the cervix
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 or have had lung problems such as pneumonitis
- have an autoimmune disease that needed treatment that reached your whole body (systemic) 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 problems with your gut and can’t absorb capsules
- have heart problems such as an abnormal heart rhythm, congestive heart failure, angina that isn’t stable or you have had a heart attack in the past year
- have had an organ transplant from a donor
- have protein in your urine
- have HIV
- have hepatitis B or hepatitis C
- have active tuberculosis
- have coughed up a large amount of blood in the past 2 weeks
- have an active infection that needs antibiotics that reach your whole body (systemic)
- have side effects from previous medical treatments
- have any other serious medical condition or mental health problem that the trial team think could affect you taking part
Other
You cannot join this trial if any of these apply. You:
- are pregnant or breastfeeding
- are sensitive to any of the drugs used in this trial or anything they contain
- have had a live vaccine in the last month
Trial design
This is an international phase 3 trial. Researchers hope that around 714 people worldwide and 45 people from the UK will agree to take part.
It is a randomised trial. The people taking part are put into 1 of the following groups at random:
- pembrolizumab, lenvatinib and chemotherapy
- pembrolizumab, dummy drug (placebo) and chemotherapy
Neither you nor your doctor are able to decide which group you are in. And neither you nor your doctor will know which group you are in. This is a double blind trial.
Everyone taking part has treatment in cycles of treatment that last 3 weeks. The first day of each cycle is called day 1.
Pembrolizumab, lenvatinib and chemotherapy (arm 1)
You have 4 cycles of treatment, taking about 3 months in total. You have each cycle in the following way. You:
- have pembrolizumab as a drip into your bloodstream (intravenously) on day 1
- have cisplatin or carboplatin as a drip into your bloodstream on day 1
- have pemetrexed as a drip into your bloodstream on day 1
- take lenvatinib as capsules that you swallow whole every day
After 4 cycles of treatment, you stop having cisplatin or carboplatin. You continue to have pembrolizumab, pemetrexed and lenvatinib. This is called maintenance treatment. You have this every 3 weeks.
You have maintenance treatment for as long as it is working, and the side effects aren’t too bad. You can have up to 35 pembrolizumab treatments.
You have regular tests to check how well the treatment is working. You might stop treatment if tests show that your cancer has disappeared. You may start a second course of pembrolizumab and lenvatinib if your cancer comes back after this. Your doctor can tell you more about this.
Pembrolizumab, dummy drug and chemotherapy (arm 2)
You have 4 cycles of treatment, taking about 3 months in total. You have each cycle in the following way. You:
- have pembrolizumab as a drip into your bloodstream on day 1
- have cisplatin or carboplatin as a drip into your bloodstream on day 1
- have pemetrexed as a drip into your bloodstream on day 1
- take a dummy drug as capsules that you swallow whole every day
After 4 cycles of treatment, you stop having cisplatin or carboplatin. And continue to have pembrolizumab, pemetrexed and dummy drug every 3 weeks (maintenance treatment).
You continue to have maintenance treatment for as long as it is working, and the side effects aren’t too bad. You can have up to 35 pembrolizumab treatments.
You may also be able to have a second course of treatment with pembrolizumab and dummy drug if your cancer comes back after you stop treatment. Your doctor can tell you more about this.
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
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:
- at set times during the trial
- at the end of treatment
Researchers want to:
- look for certain proteins (biomarkers) that can help to tell how well the treatment is working
- find out what happens to the drugs inside your body (pharmacokinetics)
- 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. You need to have a new sample taken if there isn’t a suitable sample available.
Researchers want to look for certain proteins (biomarkers) in the cancer.
Hospital visits
You see a doctor and have some tests before taking part. These tests might include:
- a physical examination
- heart trace (ECG)
- a heart scan (MUGA or ECHO)
- blood tests
- urine test
- a CT scan and MRI scan
During treatment, you see the trial team on day 1 and day 15 of your treatment cycle. This continues for 2 months. You then see the trial team every 3 weeks. You have blood tests and a physical examination every time you see them.
You have a CT scan every 6 weeks for 4 months. You then have a CT scan:
- every 9 weeks for a year
- then every 12 weeks for a year
This continues for as long as the treatment is helping you and the side effects aren’t too bad.
When you finish treatment, you see the trial team after a month. You then see or speak with the trial team every 3 months.
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 and lenvatinib affect 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.
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 that can cause muscle cramps and feeling sick
We have more information about the possible side effects of pembrolizumab.
The most common side effects of lenvatinib are:
- a stroke or bleeding in the brain that might cause numbness or weakness on one side of your body
- a blood clot in the veins of your legs or lungs
- heart problems such as palpitations, or a heart attack
- an abnormal opening (fistula) between organs or to the outside of your body
- a hole in your bowel (bowel perforation)
- bleeding from the gut
- feeling or being sick
- diarrhoea
- loss of fluid in your body (dehydration)
- shortness of breath
- liver problems which may cause yellowing of the skin and eyes (jaundice), tiredness, fever and confusion
We also have information about the possible side effects of:
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
Dr Samreen Ahmed
Supported by
Merck Sharp & Dohme (MSD)
Eisai
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
Last review date
CRUK internal database number:
16221
Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.
