A trial of pembrolizumab with chemotherapy for cancer of the bile duct or gallbladder (KEYNOTE 966)

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

Gallbladder cancer

Secondary cancers

Status:

Closed

Phase:

Phase 3

This trial is looking at adding pembrolizumab to chemotherapy for cancer of the bile duct or gallbladder (the biliary tract).

It is for people whose cancer:

has spread into surrounding tissues and they can’t have surgery to remove it
has spread elsewhere in the body

This is advanced cancer.

More about this trial

Bile duct cancer and gallbladder cancer are known as biliary tract cancers.

Doctors treat advanced biliary tract cancer with chemotherapy. The usual treatment includes the chemotherapy drugs gemcitabine and cisplatin. Doctors want to improve treatment for people with advanced biliary cancer. In this trial they are looking at adding a drug called pembrolizumab to chemotherapy.

Pembrolizumab is an immunotherapy drug Open a glossary item . It works by blocking a protein called PD-L1. This helps the body’s immune system to recognise and kill cancer cells.

In this trial some people have pembrolizumab, gemcitabine and cisplatin. And some have a dummy drug (placebo) Open a glossary item , gemcitabine and cisplatin. Researchers think that having pembrolizumab with chemotherapy might work better. But they aren’t sure so want to find out more.

The main aims of the trial are to:

find out if adding pembrolizumab to chemotherapy improves treatment for advanced biliary tract 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 bile duct cancer or gallbladder cancer that has spread into surrounding tissues and can’t be removed with an operation or the cancer has spread elsewhere in the body
can see and measure the cancer on a scan
have a sample of tissue available for the trial team to do some tests on or you are willing to give a new sample from an area that hasn’t been treated with radiotherapy
are fit and well but may not be able to do heavy physical work (performance status 0 and 1)
have satisfactory blood test results
you are willing to use reliable contraception during treatment and after you finish treatment for 4 months if you are a man and there is any chance your partner could become pregnant. Women should use reliable contraception during treatment and for 4 months after you finish pembrolizumab or 7 months after you finish chemotherapy if there is any chance you could become pregnant.
are at least 18 years of age

Who can’t take part

You cannot join this trial if any of these apply.

Cancer related
You:

have already had treatment to the whole body (systemic treatment) for advanced bile duct or gallbladder cancer apart from treatment after surgery and you completed this at least 6 months before you were diagnosed with advanced or metastatic cancer
have ampullary cancer
have a type of bile duct cancer or gallbladder cancer called small cell cancer, a neuroendocrine tumour, lymphoma, sarcoma or a mucinous cancer
have cancer that has spread to the brain or spinal cord or to the tissues that surround the brain (carcinomatous meningitis)
have had pembrolizumab or a similar drug in the past
have had an experimental treatment in the 4 weeks before going into a treatment group in this trial
have another cancer that is getting worse or needed treatment in the last 3 years unless you have basal cell cancer , squamous cell cancer or carcinoma in situ (CIS) of the breast or cervix

Medical conditions
You:

have an autoimmune disease that needed treatment such as steroids or treatments that damp down the immune system. You might be able to take part if you have a thyroid gland adrenal gland or pituitary gland problems that are controlled with medication
have had radiotherapy within 2 weeks of starting treatment
have side effects from radiotherapy that aren’t getting better
take steroids and you have pneumonitis caused by radiotherapy
have a problem with your immune system or you are having long term steroid treatment of more than 10mg of prednisolone each day in the 7 days before starting treatment in the trial
are sensitive to pembrolizumab, gemcitabine or cisplatin
have lung inflammation from past treatment (pneumonitis) that needed treatment
have side effects from major surgery that aren’t getting better
have side effects from chemotherapy unless they are mild
have an ongoing active infection that needs treatment
have hepatitis B and hepatitis C. If you have hepatitis B only, you can join the trial but might need to have treatment for hepatitis B.
have HIV
have an active tuberculosis (TB) infection
have any other medical problem such as hearing problems or a mental health problem that the team think will affect you taking part in the trial
have a problem with drugs and or alcohol that your doctor thinks will affect you taking part in the trial

Other
You:

are pregnant, trying to become pregnant or breastfeeding
have had a live vaccination within 30 days of starting trial treatment

Trial design

This phase 3 trial is taking place worldwide. The researchers hope to find 788 people to take part including 33 from the UK.

It is a randomised trial. You are put into 1 of 2 treatment groups by a computer. Neither you nor your doctor can choose which group you are in. And neither you nor your doctor know which group you are in. It is a double blinded trial.

You have 1 of the following:

pembrolizumab, gemcitabine and cisplatin
a dummy drug (placebo) , gemcitabine and cisplatin

keynote_966.png

You have all the drugs as a drip into a vein. You have treatment in cycles Open a glossary item . Each 3 week period is a cycle of treatment.

The first day of each cycle is called day 1. On day 1 you have:

pembrolizumab or the dummy drug
gemcitabine
cisplatin

On day 8 you have:

gemcitabine
cisplatin

You have treatment for up to 2 years as long as it is working and the side effects aren’t too bad.

Some people might continue to have treatment for another year. The trial doctor can tell you more about this.

Samples for research
The researchers ask for samples of your cancer (a biopsy Open a glossary item ) that you gave when you had surgery or a previous biopsy. They also ask to take some extra blood samples. Where possible you have these at the same time as your routine blood tests.

They plan to look at:

gene changes (mutations )
substances called biomarkers to help work out why treatment might work for some people and not for others

The team might also ask to collect poo samples. But you don’t have to agree to give these samples if you don’t want to.

Quality of life questionnaires
The team ask you to fill out a questionnaire before you start treatment and at set times during treatment. The questionnaire will ask about side effects and how you’ve been feeling. This is called a quality of life study Open a glossary item .

Hospital visits

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

physical examination
blood tests
urine tests
CT scan and or an MRI scan
heart trace (ECG )
hearing test

You might need to give a tissue sample if there isn’t one available.

You have a CT or MRI scan every:

6 weeks in the first year
3 months in the second year

Follow up
When you stop treatment you see the team 1 month later for a check up.

When you stop treatment and your cancer hasn’t got worse, you see the team every 6 to 12 weeks for a check up.

If the cancer has got worse, they’ll follow you up every 3 months to see how you are getting on. This might be at a routine hospital appointment or they might phone you.

Side effects

The 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 immune system. It may cause inflammation in different parts of the body which can cause serious side effects. They could happen during treatment, or some months after treatment has finished. Rarely, these side effects could be life threatening.

If you have any of these side effects, you should tell the doctor or nurse as soon as possible. You should tell them that you are on, or have been on, an immunotherapy.

Some of the common side effects of pembrolizumab are:

itchy skin or skin rash
loose, watery poo (diarrhoea)
cough
joint or back pain
fever
tummy pain
loss of skin colour
not enough thyroid hormone so you may feel tired, gain weight, feel cold or be constipated
low levels of salt in the blood that may cause you to feel tired, confused, have a headache, muscle cramps or feel sick