A trial of pembrolizumab and chemotherapy for cancer of the stomach and cancer where the food pipe joins the stomach (KEYNOTE 859)

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

Cancer type:

Oesophageal cancer

Secondary cancers

Stomach cancer

Status:

Closed

Phase:

Phase 3

This trial is for people with stomach cancer or cancer where the food pipe joins the stomach (gastro oesophageal junction).

It is for people whose cancer:

has grown into the surrounding tissues (locally advanced) or spread to other parts of the body (advanced)
doesn’t have a large amount of proteins called HER2 on its surface (HER2 negative)

You can’t join this trial if your cancer has a large amount of HER2 proteins on its surface (HER2 positive). We have information about a trial looking at pembrolizumab and chemotherapy for people with HER2 positive stomach or gastro oesophageal junction cancer.

More about this trial

Chemotherapy is a possible treatment for stomach and gastro oesophageal junction cancer. Common chemotherapy treatments include:

cisplatin and fluorouracil (5FU)
capecitabine and oxaliplatin

Pembrolizumab is a type of immunotherapy. It works by stimulating the body’s immune system to find and attack cancer cells.

Pembrolizumab is already a possible treatment for some people with lung cancer. Doctors want to find out if it can also help people with stomach and gastro oesophageal junction cancer.

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

pembrolizumab and chemotherapy (group A)
dummy drug (placebo) and chemotherapy (group B)

The main aims of this trial are to:

find out whether pembrolizumab helps people with stomach and gastro oesophageal junction cancer
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 stomach cancer or gastro oesophageal junction cancer
your cancer has grown into the surrounding tissues (locally advanced) and can’t be removed with surgery or it has spread to other parts of the body (advanced cancer)
your cancer does not have a large amount of HER2 protein on its surface (HER2 negative)
you have at least an area of cancer that doctors can see and measure on a scan
you are willing to give a new sample of tissue (biopsy) if there isn’t a suitable sample available that doctors can test for certain proteins and biomarkers
your cancer is either PD-L1 positive or PD-L1 negative (the trial team will test a sample of tissue for this)
you are able to carry out your normal activities apart from heavy physical work (performance status of 0 or 1)
you have satisfactory blood test results
you are willing to use reliable contraception during treatment and for up to 6 months afterwards if there is any possibility that you or your partner could become pregnant
you 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 a rare type of stomach cancer called squamous cell or undifferentiated stomach cancer
have cancer spread in your brain, spinal cord or the membranes that surround your brain (carcinomatous meningitis) unless you have had treatment for it, you have stopped taking steroids 2 weeks ago and a scan showed that it has been stable for the past month
have had treatment for locally advanced or advanced cancer. You might be able to take part if it was chemotherapy before or after surgery
have had pembrolizumab or any other similar drug
have had a cancer treatment that reached your whole body (systemic treatment) in the last month
have moderate or severe side effects from previous treatment
have had radiotherapy in the past 2 weeks and you still have side effects from it (1 week if it was radiotherapy to help with symptoms, apart from radiotherapy to the brain or the spinal cord)
have had another cancer in the past 5 years apart from non melanoma skin cancer or carcinoma in situ of the breast and cervix that has been successfully treated

Medical conditions

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

are taking part, or have taken part in another clinical trial using an experimental drug or device in the past month
have an autoimmune disease that needed treatment that reached your whole body in the past 2 years, unless it was treatment to replace something that the body makes such as thyroxine or insulin
have taken drugs that damp down your immune system (steroids) in the past week, unless it was a very small dose, a cream or inhaler
have had a major surgery in the past month or you might need one during this trial
still have side effects from previous surgery
have, or have had a lung inflammation (pneumonitis) that needed treatment with steroids
have had an organ or tissue transplant from a donor
have an infection that needs treatment
have HIV
have hepatitis B or hepatitis C
have tuberculosis (TB)
have moderate or severe hearing loss if you are going to have treatment with cisplatin
have moderate or severe numbness or tingling in fingers and toes
have any other 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
have had a live vaccine in the past month
are sensitive to pembrolizumab, any of the drugs used in this trial or anything they contain

Trial design

This is an international phase 3 trial. The trial team hopes that around 1,542 people worldwide and between 28 and 35 people from the UK will agree to take part.

It is a randomised trial. Everyone taking part is put into 1 of the following groups by computer:

pembrolizumab and chemotherapy (group A)
dummy drug and chemotherapy (group B)

Neither you nor your doctor can choose which group you are in. And neither you nor your doctor will know which treatment you are having. This is a double blind trial.

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There are 2 different chemotherapy treatments that you can have:

cisplatin and fluorouracil (5FU)
capecitabine and oxaliplatin

Your doctor can tell you which treatment you will have.

How you have pembrolizumab or the dummy drug

You have pembrolizumab or the dummy as a drip into a vein (intravenously). You have it every 3 weeks. It takes about 30 minutes each time you have it.

You continue to have pembrolizumab or the dummy drug for as long as it is helping you and the side effects aren’t too bad. You can have up to 35 treatments (about 2 years).

If you are in the pembrolizumab group (group A), you might be able to have another year of pembrolizumab if your cancer gets worse after:

completing 2 years of treatment
you stopped treatment because there was no sign of your cancer

This is called the second course (retreatment) phase. Your doctor can tell you more about this.

How you have cisplatin and fluorouracil (5FU)

You have cisplatin and 5FU as drips into a vein. It takes:

between 1 and 2 hours to have cisplatin
about 5 days to have 5FU

You need to stay in hospital for 5 days to have 5FU if you don’t have a central line. If you have a central line, you may be able to have treatment through a pump which means you can have treatment at home.

You have cisplatin and 5FU in cycles of treatment. Each cycle lasts 3 weeks.

You may continue to receive 5FU if the doctor thinks it will help and is safe.

You have up to 6 treatment cycles of cisplatin. You might have more if your doctor thinks it will help.

You have each cycle in the following way. You have:

cisplatin on the 1st day of each cycle
5FU continuously over 5 days starting on the 1st day of each cycle

How you have capecitabine and oxaliplatin

You have capecitabine and oxaliplatin as cycles of treatment. Each cycle lasts 3 weeks. You have up to 8 cycles taking about 6 months. You might have more if your doctor thinks it will help.

You have each cycle of treatment in the following way. You have:

oxaliplatin as a drip into your vein every 3 weeks, taking around 2 hours each time you have it
capecitabine as tablets that you swallow whole twice a day, for 2 weeks, followed by a week of no treatment

Tissue and blood samples

The trial team will ask for a sample of tissue of your cancer. This can be from when you had a biopsy or a previous surgery to remove the cancer. You need to have a new tissue sample taken if there isn’t a suitable sample available.

You have some extra blood tests as part of this trial. You have them before the start of treatment and at set times during this trial. Doctors want to look for certain substances in the blood (biomarkers) that can help to tell how well treatment is working.

Quality of life questionnaires

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

every 3 weeks for up to 13 weeks
every 6 weeks until you finish treatment
a month after you finish treatment

Each questionnaire asks about how you are feeling and the side effects you might have. You complete the questionnaires on a tablet.

Hospital visits

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

a physical examination
CT scan or MRI scan
a hearing test (if you are going to have cisplatin)
heart trace (ECG)
blood tests
urine test

During treatment, you see the trial team every 3 weeks. You have a physical examination and blood tests every time you see them. You also have a CT scan or MRI scan every 6 weeks.

After you finish treatment, you see the trial doctor after a month. You have blood tests and your doctor will check how you are. You then see or speak with the trial team every 3 months or more often.

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, weight gain, feeling cold and hard infrequent poo
low levels of salt in your body that may cause you to feel tired, have headaches, muscle cramps and feel sick

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