A trial of chemotherapy, pembrolizumab and lenvatinib for oesophageal cancer has spread (LEAP-014)
Cancer type:
Status:
Phase:
This trial is comparing 2 combinations of treatment for cancer of the food pipe (oesophagus) that has spread to another part of the body.
One combination of treatment is chemotherapy and pembrolizumab. The other combination is chemotherapy, pembrolizumab and lenvatinib.
More about this trial
Oesophageal cancer that has spread elsewhere in the body is called metastatic or advanced cancer.
Chemotherapy is a 
for advanced oesophageal cancer. You might also have a drug called pembrolizumab with chemotherapy. Pembrolizumab is an . It helps your find and kill cancer cells.
Doctors are trying to improve treatment for people with advanced cancer of the oesophagus. They are looking at adding a called lenvatinib to chemotherapy and pembrolizumab.
Lenvatinib is a type of targeted drug called a cancer growth blocker. It stops signals that cancer cells use to divide and grow. It is already a treatment for some other types of cancer that have spread elsewhere in the body.
In this trial some people have chemotherapy and pembrolizumab. And some have chemotherapy, pembrolizumab and lenvatinib.
The main aims of the trial are to find out:
- which combination of treatment works best
- how safe it is to add lenvatinib to chemotherapy and pembrolizumab
- what the side effects are
- how treatment affects quality of life
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
squamous cell cancer of the food pipe (oesophagus) that has spread elsewhere in the body - have cancer that your doctor can measure on a scan
- have a sample of tissue (
biopsy ) available for the trial team to do some tests on. Or if this isn’t available you are willing to provide a fresh sample. - have blood pressure that is well controlled with or without medication
- have satisfactory blood test results
- are well enough to carry out all your normal activities but might not be able to do heavy physical work (performance status 0 to 1)
- are willing to use reliable contraception during the trial and for a period 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 already had treatment for oesophageal cancer that has grown into surrounding tissues or spread elsewhere in the body. You might be able to take part if you had
standard treatment just before or after surgery. The trial team will check this. - have cancer that has grown into surrounding tissue but hasn’t spread elsewhere in the body
- have
adenocarcinoma of the oesophagus - have cancer that has grown into nearby organs such as the main artery in the heart or the windpipe (trachea)
- have cancer that surrounds a major blood vessel or areas of cancer that have air in them
- have cancer that has spread to the brain or the tissues surrounding the brain. You might be able to take part if you have had treatment and the cancer is stable.
- have had pembrolizumab, lenvatinib or a similar drug in the past
- have had recent radiotherapy before starting trial treatment or you have inflammation of the lung (pneumonitis) due to radiotherapy
- are having an experimental drug or using a device as part of a clinical trial within 4 weeks of the first dose of trial treatment
- have another cancer that is getting worse or needed treatment in the last 3 years. You can join if you have
non melanoma skin cancer , carcinoma in situ of the breast or cervix that has been successfully treated.
Medical conditions
You cannot join this trial if any of these apply. You:
- have had a heart attack in the last year or a significant
heart problem that needs treatment. The trial team check if you have a heart condition before you join the trial. - have had a stroke in the last year
- have a risk of bleeding or you have had a bleed from your tumour in the last few weeks
- have had a significant bleed from your tummy or you have vomited blood within 3 weeks of the first dose of trial treatment
- have areas of fluid on your lungs, heart or tummy that need frequent drainage
- have a blockage in your gut, problems eating or drinking or problems swallowing medication
- can’t absorb lenvatinib for any reason. For example you have a problem with your
digestive system . - have a
stent in your oesophagus - have had major surgery or a bad injury within 3 weeks of having trial treatment
- are having any antiviral treatment such as brivudine or sorivudine
- have a certain amount of protein in your urine. Your doctor will test for this.
- have a problem with how your
immune system works, you are having long term steroid treatment or any other treatment that damps down the immune system - have had an
organ transplant or a stem cell transplant with somebody else’s cells (allogeneic transplant ) - have an active
autoimmune condition that needed treatment in the past 2 years apart from certain ones. Your doctor will know which ones these are. - have lung inflammation (pneumonitis) not caused by a lung infection or interstitial lung disease. Or you had treatment for this in the past.
- have diarrhoea that isn’t controlled
- have moderate to severe numbness or tingling in your hands or feet
- are known to have HIV, hepatitis B, a known hepatitis C infection or any other severe infection that needs treatment
- have any other medical condition or mental health problem that could affect you taking part in this trial
Others
You cannot join this trial if any of these apply. You:
- have had a live
vaccine within 30 days of starting trial treatment - are allergic to any of the drugs in the trial or anything they contain
- have a problem with drugs or alcohol that could affect you taking part in the trial
- have lost more than 20 percent (a fifth) of your body weight in the last 3 months
- are pregnant or breastfeeding
- plan to donate sperm during the trial and for a period after
Trial design
This phase 3 trial is taking place worldwide. The team need to find 862 people to take part including 35 from the UK.
It is a randomised trial. A computer puts you into a treatment group. Neither you nor your doctor will be able to decide which group you are in. There are 2 treatment groups.
You have one of the following:
- chemotherapy, pembrolizumab and lenvatinib
- chemotherapy and pembrolizumab
You:
- have chemotherapy every 2 or 3 weeks for 12 weeks
- have pembrolizumab as a drip into a vein once every 6 weeks
- take lenvatinib capsules that you swallow whole every day
You have one of the following combinations of chemotherapy:
• 5FU and oxaliplatin (FOLFOX) or
• 5FU and cisplatin
Your doctor decides which combination of chemotherapy will work best for you. These are all standard chemotherapy drugs for cancer of the oesophagus.
You start all your treatment on the same day. You have 12 weeks of chemotherapy in total. You then continue to have pembrolizumab on its own or pembrolizumab and lenvatinib. This depends on which group you are in. You have this for up to 2 years as long as it is working and the side effects aren’t too bad.
You have regular tests to check how well treatment is working. You might stop treatment if tests show that your cancer has disappeared. You may start a second course of pembrolizumab if your cancer comes back after this. You might also have a second course of lenvatinib. Your doctor can tell you more about this.
Blood samples for research
The researchers will ask to take some extra blood samples. Where possible, you have these at the same time as your routine blood tests.
They plan to use the samples to:
- see how well treatment is working
- look at
genes to understand more about oesophageal cancer - look for substances called
biomarkers to help work out why treatment might work for some people and not for others - see what happens to treatment in the body
Quality of life
The trial team ask you to fill out a questionnaire:
- before you start treatment
- at set times during treatment
- at set times after treatment
The questionnaire asks about side effects and how you’ve been feeling. This is called a quality of life study.
Hospital visits
You see the doctor and have tests before you can take part. These include:
- blood tests
- urine tests
- a
physical examination - heart trace (ECG)
- heart scan (echocardiogram) or
MUGA scan - endoscopy to examine your throat, stomach and oesophagus
- CT scan or MRI scan
You have chemotherapy and pembrolizumab at the hospital on the day care ward. Each visit will take about 4 to 6 hours.
You see the doctor for a check up and blood tests:
- about once a week for 18 weeks and then
- every 3 weeks for up to 2 years
You have a scan every:
- 6 weeks in the first year of treatment and then
- every 9 weeks after that
You stop having trial scans if your cancer gets worse.
You see the doctor a month after stopping treatment.
Follow up
You have follow up every 3 months if you stopped treatment because your cancer got worse.
If you had the full course of treatment or stopped treatment but the cancer didn’t get worse, you have follow up as follows:
- every 6 weeks for the first year and then
- every 9 weeks
This is until your cancer gets worse or you start a new treatment.
You might see the team at a routine hospital appointment or they may call you to see how you are getting on.
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 These side effects could happen during treatment or months after treatment has finished. Rarely, these side effects could be life threatening. Your doctor or nurse can explain what these side effects are, the risk of them happening and what to look out for. |
The most common side effects of pembrolizumab are:
- itchy skin or skin rash
- diarrhoea
- cough
- joint, back or tummy pain
- high temperatures (fever)
- loss of skin colour
- not enough thyroid hormone. You may feel tired, gain weight, feel cold, or have constipation.
- low levels of salt in the blood. You may feel tired, confused, have a headache, have muscle cramps and feel or be sick.
The team will ask to take a photo if you get a skin rash. They may ask to take more photos until it gets better.
The most common side effects of lenvatinib include:
- high or low blood pressure
- loss of appetite or weight loss
- feeling or being sick
- constipation or diarrhoea
- tummy (abdominal) pain or indigestion
- tiredness (fatigue)
- dry, sore, or inflamed mouth or throat
- high levels of protein in the urine
- hoarse voice
- headache
- redness, soreness and swelling of the skin on the hands and feet
- joint, muscle, arm, leg or back pain
- cough
- an increased risk of bruising or bleeding
- swelling of the legs
- not enough thyroid hormone. You may feel tired, cold, have dry skin, or develop hair loss
- skin rash
- dizziness
- odd taste sensation
- trouble sleeping
- hair loss
- urine infections
- low levels of potassium or calcium in the body
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
- a blood clot in the leg causing swelling of the calf that is warm and tender
- a 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 such as heart palpitations or a heart attack - an abnormal opening between two parts or organs of the body (a fistula) or a hole in the wall. This can cause severe abdominal pain.
- bleeding inside the body, mainly the gut, causing black, tarry or bloody poo
- severe loss of water from the body (dehydration) and kidney failure. Diarrhoea and being sick a lot can cause this.
- a decreased ability of heart to pump causing severe shortness of breath
liver problems or failure. This can cause 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
The trial doctor will talk to you about all the side effects of treatment. You will have a chance to ask any questions you may have.
We have more information about:
Location
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.
Chief Investigator
Professor Wasat Mansoor
Supported by
Merck, Sharp & Dohme
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
