A trial looking a lenvatinib and pembrolizumab for people with womb cancer (KEYNOTE-775)

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

Cancer type:

Secondary cancers

Womb (uterine or endometrial) cancer

Status:

Closed

Phase:

Phase 3

This trial is for women with womb cancer that has come back or spread to other parts of the body (advanced womb cancer). Womb cancer is also called uterine or endometrial cancer.

It is for people who have had at least one type of treatment with chemotherapy that included a platinum drug. Platinum chemotherapy includes the drugs:

cisplatin
carboplatin
oxaliplatin

More about this trial

Treatment for advanced womb cancer is usually chemotherapy. It uses cytotoxic drugs to slow down the cancer and help with symptoms. Doxorubicin and paclitaxel are 2 possible chemotherapy treatments.

Doctors are looking for new ways to help women with advanced womb cancer. In this trial, they are looking at lenvatinib and pembrolizumab.

Lenvatinib (Lenvima) is a targeted drug. It works by blocking certain proteins that help cells to grow blood vessels. All cancer cells need blood vessels to survive and grow.

Pembrolizumab (Keytruda) is a type of immunotherapy. It stimulates the body’s immune system to fight cancer cells.

Everyone taking part in this trial has 1 of the following:

lenvatinib and pembrolizumab
doxorubicin or paclitaxel

The main aim of this trial is to find out whether lenvatinib and pembrolizumab help people with advanced womb cancer.

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 womb cancer that has come back (recurrent) or spread to other parts of the body (metastatic)
your cancer got worse after treatment with a platinum chemotherapy such as cisplatin or carboplatin
there is a suitable tissue sample available (archival tumour sample) that doctors can use to look for certain changes (or you are willing to have a new sample taken)
you have at least 1 area of cancer that can be seen and measured on a scan
you are well enough to carry out your normal activities, apart from heavy physical work (performance status of 0 or 1) and this hasn’t changed in the past week
you have satisfactory blood tests results
your heart is working well
you are at least 18 years old
you are willing to use reliable contraception during treatment and for up to 6 months afterwards if there is any possibility that you could become pregnant

Who can’t take part

You cannot join this trial if any of these apply.

Cancer related

You can’t take part if:

you have a type of womb cancer called carcinosarcoma, endometrial leiomyosarcoma or endometrial stromal sarcoma
you have cancer spread in your brain unless you have had treatment, it hasn’t got worse in the past 4 weeks and you are no longer taking steroids
your cancer has spread to a major blood vessel and your doctor thinks you have a high risk of bleeding
you have had a large bleeding from your cancer in the past 2 weeks
you have had more than 1 chemotherapy regimen that included a platinum drug unless you had it before or after your main treatment (adjuvant or neoadjuvant treatment)
you have had chemotherapy, surgery or a targeted drug in the past 28 days
you have had radiotherapy in the past 3 weeks, or 2 weeks if it was radiotherapy to help with symptoms (palliative)
you have moderate or severe side effects from previous cancer treatment apart from hair loss and numbness or tingling in fingers and toes
have had pembrolizumab or any other similar drug
have taken part in another clinical trial looking at pembrolizumab and lenvatinib
you have had another cancer in the past 2 years apart from early cancer (carcinoma in situ) of the cervix, breast and bladder or a non melanoma skin cancer

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 treatment (drug or device) in the past 4 weeks
have problems with your gut and you can’t absorb tablets
have had, or you currently have, lung problems such as pneumonitisthat needed treatment with steroids
have an abnormal opening (fistula) between organs or to the outside of your body
have coughed up a large amount of blood in the past 2 weeks
have heart problems such as high blood pressure (hypertension) that isn’t controlled, unstable angina, an abnormal heart rhythm or you have had a heart attack in the past 12 months
have had a stroke in the last year
have an infection and you need antibiotics that reach your whole body
have taken drugs that damp down your immune system (immunosuppressants) in the past week, unless it was a very small dose
have an autoimmune disease that needed treatment in the past 2 years, apart from treatment to replace something that the body makes such as insulin or thyroxine
have had an organ transplant or a bone marrow or stem cell transplant from a donor (allogeneic transplant)
have protein in your urine
have HIV
have hepatitis B or hepatitis C
have any other medical condition or mental health problem that the trial team think could affect you taking part
take an amount of drugs or drink an amount of alcohol that is a concern for the trial team

Other

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

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

Trial design

This is an international phase 3 trial. Researchers hope that around 780 people worldwide and 35 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 treatment groups by computer:

lenvatinib and pembrolizumab
doxorubicin or paclitaxel

Neither you nor your doctor are able to decide which group you are in.

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Lenvatinib and pembrolizumab

You have:

• lenvatinib as tablets that you swallow whole every day

• pembrolizumab as a drip into a vein over 30 minutes, every 3 weeks

You continue lenvatinib and pembrolizumab for as long as it helps you and the side effects aren’t too bad. You can have treatment for up to 2 years.

After 2 years, you may be able to continue having treatment for another year. This is called the second course treatment. Your doctor can tell you more about this.

Doxorubicin or paclitaxel

You have doxorubicin or paclitaxel as a drip into your vein over an hour. You have:

doxorubicin every 3 weeks
paclitaxel every week for 3 weeks, followed by a week off

Your doctor can tell you which treatment you have. This continues for as long as treatment is helping you and the side effects aren’t too bad.

Blood tests

You have extra blood tests as part of this trial. You have them before the start of treatment and then:

every 3 or 4 weeks
at the end of treatment

Doctors want to look for certain proteins (biomarkers) that can tell how well the treatment is working. And find out what happens to lenvatinib in your body (pharmacokinetics).

Tissue sample

The trial team 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 changes (mutations) in a gene called the mismatch repair gene.

Quality of life

Everybody taking part completes quality of life questionnaires before the start of treatment and:

every 3 to 4 weeks
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.

Hospital visits

You see a doctor and have some tests before taking part. These tests might include:

a physical examination
heart trace (ECG) and heart scan (MUGA)
blood tests
urine test
a CT scan or MRI scan
a bone or brain scan (if you have cancer spread in your bones or brain)

During treatment, you see the trial team regularly. How often you see them depends on the treatment you have. You have blood tests and a physical examination every time you see them.

You have a CT scan or MRI scan every 8 weeks. You may also have a bone and brain scan if you have cancer spread in the bones or brain.

Your treatment continues for as long as it is helping you and the side effects aren’t too bad.

When you finish treatment, you see the trial doctor 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 has an effect on the immune system. This may cause inflammation in different parts of the body which can cause serious side effects.

These side effects could happen during treatment, or some months after treatment has finished. In some people, these side effects could be life threatening.

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 temperatures
thyroid problems that can cause tiredness and feeling cold
low levels of salt in your body that may cause you to feel tired, have headaches and muscle cramps

We have more information about the possible side effects of pembrolizumab.

The 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)
heart problems that can cause shortness of breath
liver problems which may cause yellowing of the skin and eyes (jaundice), tiredness, fever and confusion