"I was delighted to take part in a clinical trial as it has the potential to really help others in the future.”
A trial of durvalumab with chemotherapy for biliary cancer (TOPAZ-1)
Please note - this trial is no longer recruiting patients. We hope to add results when they are available.
More about this trial
Biliary cancer that can’t be removed by surgery or has spread to another part to the body is called advanced biliary cancer. Doctors treat advanced biliary cancer with chemotherapy. Two of these chemotherapy drugs are gemcitabine and cisplatin.
Durvalumab is an immunotherapy drug. It works by blocking a protein called PD-L1. This helps the body’s immune system to recognise and kill cancer cells.
Researchers think that the combination of durvalumab, gemcitabine and cisplatin might be better than gemcitabine and cisplatin for advanced biliary cancer.
In this trial some people will have durvalumab, gemcitabine and cisplatin. And others will have a dummy drug (placebo), gemcitabine and cisplatin.
The aims of the trial are to find out:
- how well durvalumab, gemcitabine and cisplatin work for advanced biliary cancer
- what happens to durvalumab in the body when used with gemcitabine and cisplatin
- how acceptable this treatment is
- what the side effects are
- how it affects quality of life
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 one of the following cancers:
And at least one of the following applies. You:
- have cancer that has grown into the surrounding tissue and cannot be removed by surgery
- have cancer that has spread to another part of your body (metastatic)
- had your cancer removed by surgery with the aim to cure more than 6 months ago and it has come back (recurred). If you had further treatment after surgery it was completed more than 6 months ago.
And all of the following apply. You:
- have at least 1 area of cancer that the doctor can measure on a scan
- have satisfactory blood test results
- are fit and well but may not be able to do heavy physical work (performance status 0 and 1)
- weigh more than 30kg (4st 7lb)
- are willing to use reliable contraception during treatment and for 6 months after if you have chemotherapy and for 3 months if you have durvalumab
- are at least 18 years old
Who can’t take part
You cannot join this trial if any of these apply.
- have ampullary cancer
- have cancer that has spread to the brain or spinal cord
- have cancer that has spread to the membranes (meninges) surrounding the brain
- have ongoing moderate side effects of previous cancer treatment apart from hair loss and lightening of your skin (vitiligo)
- are currently having cancer treatment such as chemotherapy, hormone therapy, a targeted drug, immunotherapy or radioembolisation
- had radiotherapy apart from radiotherapy after surgery to remove your cancer
You cannot join this trial if any of the following apply. You:
- have had an organ transplant
- have an autoimmune disease or inflammatory disorder such as inflammatory bowel disease, diverticulitis, systemic lupus erythematosus or rheumatoid arthritis. You might be able to join if you have vitiligo, hair loss, hypothyroidism that is stable with hormone replacement therapy, ongoing skin condition not needing treatment that affects the whole body, celiac disease controlled by diet only or there has been no sign of this disease for at least 5 years
- have an ongoing or active infection
- have or have had heart problems such as a congestive heart failure that is causing symptoms, angina not controlled or problems with how your heart beats (rhythm) that isn’t controlled
- have high blood pressure that isn’t controlled
- have problems with your lungs such as scarring
- have had another cancer in the past 5 years apart from successfully treated non melanoma skin cancer, lentigo maligna, carcinoma in situ or another cancer that was treated with the aim to cure and there hasn’t been a sign of it in the past 5 years
- have an active disease that affects your immune system such as HIV
- 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 hepatitis B and hepatitis D
- have tuberculosis (TB)
- have major surgery within 28 days of starting treatment
- are taking medication such as steroids that damp down your immune system within 14 days of starting treatment apart from inhalers, creams, injections into a joint and tablets with a dose of 10mg or less a day or used once only to stop an allergic reaction before a procedure such as a CT scan
- have used an experimental drug or device in the past 3 months as part of another clinical trial
- are taking part in another clinical trial unless it is an observational study or you are in follow up
- have had durvalumab before
- are allergic or sensitive to the drugs or any of their ingredients used in this trial
- have any other medical or mental health condition that your doctor or the trial team think will affect you taking part in the trial
You cannot join this trial if any of the following apply. You:
- had a live vaccine within 30 days of starting treatment, might have a live vaccine during treatment or within 30 days after finishing treatment
- are pregnant or breastfeeding
This is an international phase 3 trial. The trial team need 474 people to join with 24 people from the UK.
This is a randomised trial. Everyone is put into 1 of 2 treatment groups. Neither you nor your doctor can choose which group you are in. And neither you nor your doctor will know which group you are in. It is a double blinded trial.
- 316 people have durvalumab with gemcitabine and cisplatin
- 158 people have a dummy drug (placebo) with gemcitabine and cisplatin
You have treatment in cycles. Each 3 week period is a cycle of treatment. You have all the drugs as a drip into a vein.
You have all 3 drugs at the start of each cycle of treatment. On day 8 of each cycle of treatment you have gemcitabine and cisplatin again.
After 8 cycles of treatment (24 weeks) you stop having gemcitabine and cisplatin. You continue having durvalumab or the dummy drug as long as it is helping and the side effects aren’t too bad.
Quality of life
You fill in a few questionnaires when you start treatment and then every:
- 3 weeks for 24 weeks
- 4 weeks to 52 weeks
- 8 weeks until your cancer gets worse or the end of the trial
The questions ask about how you are feeling and any side effects you might have. You fill in the questionnaires on an electronic device like a tablet.
Tissue and blood samples
The team will ask for a piece of the cancer tissue that was taken when you were first diagnosed. If this isn’t available you must agree to have a fresh piece of tissue (biopsy) taken. They use this to check that your cancer has the protein PD-L1.
You also give a number of blood samples during the trial. These are used to:
- check the level of durvalumab
- see if there are any antibodies to durvalumab
- look for substances (biomarkers) that might show how well durvalumab is working
You must agree to all of the above samples to take part in the trial.
The team will ask for more tissue samples if your cancer gets worse. They will also ask for extra blood samples to look at the DNA in your cells.
You don’t have to agree these samples if you don’t want to. You can still take part in the main trial.
You see the doctor to have some tests before taking part. These tests include:
You see the doctor regularly during treatment for blood tests and to see how you are. You have an MRI scan or CT scan every:
- 6 weeks for 24 weeks
- then every 8 weeks
A month after treatment has finished you see the doctor who will ask how you are and to have:
- a physical examination
- for blood tests
You then see the doctor at:
- 2 months
- 3 months
- 4 months
- 6 months
- 8 months
- 10 months
- 1 year
- and then every 6 weeks until your cancer gets worse
Durvalumab works by boosting the immune system. This can cause side effects that might happen when you have it, hours after, days after or even weeks after. Contact your health advice line, doctor or a member of the trial team if you have any side effects.
Your doctor and the trial team will monitor you closely when you are having treatment.
The most common side of durvalumab include:
- rash and or dry, itchy skin
- change to the way your liver works
- feeling or being sick
- tummy (abdominal) pain
- build up of fluid in the body causing swelling
- chest infections
- loss of appetite
- shortness of breath
- painful muscles and joints
- high temperature (fever)
Your doctor or a member of the trial team will talk to you about the side effects of all the drugs before you agree to take part.
How to join a clinical trial
Professor Juan Valle