A trial looking at lenvatinib and pembrolizumab for people with advanced solid tumours (LEAP-005)

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

Cancer type:

Bile duct cancer

Biliary tree cancers

Bowel (colorectal) cancer

Brain (and spinal cord) tumours

Breast cancer

Ovarian cancer

Secondary cancers

Stomach cancer

Status:

Closed

Phase:

Phase 2

This trial is for people with one of the following solid tumours:

breast cancer whose cells don’t have receptors for the protein Her2 and the hormones oestrogen and progesterone (triple negative breast cancer)
ovarian cancer
stomach cancer
bowel cancer
a type of brain tumour called glioblastoma multiforme (GBM)
bile duct cancer
gallbladder cancer

It is for people whose cancer continued to grow or spread to other parts of the body despite treatment (advanced solid tumours).

More about this trial

Treatment for advanced solid tumours is usually a combination of cancer drugs. The exact treatment you have depends on your cancer type and how well you are overall.

Researchers are looking for new ways to help people with advanced solid tumours. In this trial, they are looking at 2 targeted drugs called lenvatinib and pembrolizumab. Both drugs are already a possible treatment for people with certain types of solid tumours.

Targeted drugs work by ‘targeting’ differences that a cancer cell has that make them different from normal cells. Lenvatinib (Lenvima) is a type of targeted drug called a cancer growth blocker. It blocks certain proteins that help cancer cells to grow new blood vessels. All cancer cells need blood vessels to survive and grow.

Pembrolizumab is a type of cancer drug called a monoclonal antibody. It helps the immune system attack the cancer and stop it from growing.

The main aims of this trial are to:

find out how well lenvatinib and pembrolizumab work as a treatment for advanced solid tumours
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 you have 1 of the following types of cancer:

triple negative breast cancer
ovarian cancer
bowel (colorectal) cancer
a type of brain tumour called glioblastoma multiforme (GBM)
bile duct cancer
gallbladder cancer

As well as 1 of the above, all of the following must apply:

your cancer has spread to other parts of the body (metastatic) or continued to grow despite treatment
doctors think that you can’t have treatment to cure your cancer
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
you are at least 18 years old
you have satisfactory blood test results
your heart is working well and your blood pressure is normal
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 at least 4 months afterwards if there is any possibility that you or your partner could become pregnant

As well as the above, there might be specific entry conditions for your cancer type. Speak to your doctor or research nurse if you want to find out more about the entry conditions for this trial.

Who can’t take part

You cannot join this trial if any of these apply:

Cancer related

you have cancer spread in your brain or spinal cord unless you have had treatment, it has been stable for the past month and you have stopped taking steroids more than 2 weeks ago
you have a tumour in your brain stem
you have cancer spread in the thin layers (membranes) that surround the brain (carcinomatous meningitis)
your cancer has spread to a major blood vessel and your doctor thinks that you have a high risk of bleeding
you have had lenvatinib, pembrolizumab or any other similar drug
you have had anti cancer treatment that reached your whole body in the last month
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 still have moderate or severe side effects from previous anti cancer treatment, unless it is numbness and tingling in fingers and toes
you have had another cancer in the past 3 years unless it was non melanoma skin cancer or a carcinoma in situ of the cervix and breast

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
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 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
have or have had lung problems such as pneumonitis
have an active infection that needs antibiotics that reach your whole body (systemic)
have problems with your gut and can’t absorb capsules
have protein in your urine
have coughed up a large amount of blood in the past 2 weeks
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 a blood clot in one of the main blood vessels in the past year
have a wound or a break in a bone (fracture) that hasn’t healed
have had a drug that encourages the bone marrow to make white blood cells in the last 2 months such as G-CSF
have had an organ transplant from a donor
have HIV
have hepatitis B or hepatitis C
have active tuberculosis
have any other serious medical condition or mental health problem that the trial team think could affect you taking part
take an amount of drugs or alcohol that is a concern for your doctor

Other

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

are sensitive to any of the drugs used in this trial or anything they contain
have had a live vaccine in the last month
are pregnant or breastfeeding

As well as the above, there might be specific exclusion conditions for your cancer type. Speak to your doctor or research nurse if you want to find out more about the exclusion conditions for this trial.

Trial design

This is an international phase 2 trial. Researchers hope that around 180 people worldwide and 18 people from the UK will agree to take part.

Everyone taking part has lenvatinib and pembrolizumab in the following way:

you have pembrolizumab as a drip into your bloodstream (intravenously) every 3 weeks. It takes about 30 minutes to have pembrolizumab each time
you take lenvatinib capsules every day

You continue to have treatment for as long it is helping you and the side effects aren’t too bad. You can have up to 35 treatments of pembrolizumab, taking about 2 years in total. You may be able to continue to take lenvatinib after 2 years. 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 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 or MRI scan

During treatment, you 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 or MRI scan every 9 weeks for a year. You then have a CT scan or MRI scan every 3 months. If you have glioblastoma multiform (GBM), you have an MRI scan of your brain every 6 weeks, for 4 months. You then have an MRI of your brain:

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 that can cause yellowing of the skin and eyes (jaundice), tiredness and fever
changes in your brain that can cause confusion, sleepiness (drowsiness) and loss of consciousness due to severe liver problems
kidney problems that can cause a reduction in the amount of urine you make and swelling of your legs, ankles and feet (kidney failure)