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:
Status:
Phase:
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 
. It works by blocking a protein called PD-L1. This helps the body’s to recognise and kill cancer cells.
In this trial some people have pembrolizumab, gemcitabine and cisplatin. And some have a dummy drug (, 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
You have all the drugs as a drip into a vein. You have . 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 ) 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 .
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
We have information about the side effects of:
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
Dr John Bridgewater
Supported by
Merck Sharp & Dohme
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
