A trial of targeted drugs for bile duct cancer and gallbladder cancer (SAFIR-ABC10)

Cancer type:

Bile duct cancer
Biliary tree cancers
Gallbladder cancer

Status:

Open

Phase:

Phase 3

This trial is looking at targeted drugs Open a glossary item for bile duct cancer and gallbladder cancer that has spread to another part of the body or has come back after treatment. 

Bile duct cancer and gallbladder cancer are also called biliary tree cancers. 

More about this trial

The standard treatment Open a glossary item for bile duct cancer and gallbladder cancer that has spread or come back is either a combination of:

This works well but unfortunately the cancer can start to grow again in some people. So researchers are always looking for new treatments for people in this situation. 

We know from research that cancer cells have differences in their genes that make them unlike normal cells. Genes of one cancer are different to those of another. This is called the genetic makeup of the cancer. Every person’s cancer has its own genetic makeup. These differences or features of the cancer cells might explain why treatment works better for some people and not so well for others. 

In this trial researchers are looking at these genetic differences. They want to look at choosing a cancer drug that target them to find out if can help stop the cancer coming back. This is called personalised medicine or precision treatment. 

There are 2 parts to this trial, the:

  • screening part
  • randomised part

You must be in the screening part to be able to join the randomised part. 

During the screening part, the team test the cancer cells to look for any differences that they could target with treatment. 

In the randomised part, if your cancer has a certain genetic difference, you will have either the standard treatment or a targeted drug Open a glossary item

The aims of this trial are to find out:

  • whether having a targeted drug based on your cancer's genetic differences works better than the standard treatment by itself to stop the cancer coming back 
  • more about the side effects of the targeted drugs
  • how these treatments affect quality of life Open a glossary item

Who can enter

The following bullet points are a summary of 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

There are 2 parts to this trial, the:

•    screening part
•    randomised part, not yet open to recruitment

Each part has its own entry conditions

To take part in this trial you must:

  • have bile duct cancer or gallbladder cancer that has come back or spread to another part of the body. You cannot take part if your cancer started where the bile duct meets the pancreatic duct (ampullary cancer). 
  • are at least 18 years old

Screening part
You may be able to join the screening part of this trial if the following also apply. You:

  • have had a sample of tissue (biopsy Open a glossary item) taken of your cancer that the team can access and test. If this is not the case, then you must be willing to have a new biopsy taken. 
  • are able to have the standard treatment. Or you have just started the first cycle of the standard treatment Open a glossary item. Your doctor will know this. 
  • are fully active but might not be able to do heavy physical work (performance status 0 or 1)

Who can’t take part

Screening part
You cannot join the screening part of the trial if any of these apply. You:

  • are able to have surgery or radiotherapy to treat your cancer 
  • are not able to have the standard treatment
  • have had more than the first cycle of the standard treatment
  • have had treatment to relieve or control the symptoms (palliative treatment) from your cancer. If you had a chemotherapy called capecitabine as palliative treatment you can take part if you stopped it at least 6 months before joining this trial. 
  • have already had treatment with any of the drugs used in this trial. Your doctor will know if you have. 
  • have had another cancer. This is apart from successfully treated in situ carcinoma Open a glossary item of the cervix and non melanoma skin cancer Open a glossary item. You can join if you had cancer that was treated with the aim to cure and there has not been any sign of it for at least 5 years and it is not likely to come back. 
  • are pregnant or breastfeeding
  • have any other medical conditions, mental health conditions or other circumstances that might affect you taking part in the trial  

Who can take part 

Randomised part
You may be able to join the randomised part of this trial if the following also apply.

  • You have at least 1 change in the cancer cells that means you are able to have one of the targeted drugs used in this trial. The team use the tissue sample from the screening part to find this out. Your doctor will be able to tell you this. 
  • After 4 cycles of the standard treatment your cancer has stayed the same (stable disease) or has shrunk (responded to treatment). Your doctor will tell you this. 
  • You have at least 1 area of cancer that the doctor can measure. Or after 4 cycles of the standard treatment there is no sign of cancer (a complete response).
  • You have satisfactory blood test results. 
  • Your kidneys, liver and heart work well enough. Your doctor will do tests to find this out.
  • Your bile duct Open a glossary item drains well and there is no sign of an ongoing infection. Your doctor can tell you this. 
  • You are willing to use reliable contraception during treatment and for a period of time after if there is any chance you or your partner could become pregnant. 
  • You are fully active but might not be able to do heavy physical work (performance status 0 or 1).

Who can’t take part

Randomised part
You cannot join the randomised part of the trial if any of the following apply.

  • Your cancer got worse before you were put in a treatment group in the trial (randomised Open a glossary item). 
  • You did not complete 4 cycles of standard treatment. 
  • You have ongoing moderate to severe side effects. This is apart from hair loss.
  • You have symptoms of cancer spread to the brain and spinal cord, or the cancer has spread there and it has not been treated. You have had radiotherapy to treat cancer spread to the brain and spinal cord within 4 weeks before joining the trial. If you have had treatment for cancer spread to the brain and spinal cord, you can take part as long as you are not taking steroids Open a glossary item or medication to control seizures (fits) and the cancer spread is stable for at least 4 weeks before joining the trial. 
  • You have cancer spread to the tissue surrounding the brain. 
  • You are allergic or sensitive to the targeted drugs, or their ingredients, used in the randomised part of the trial. You might be able to take part if you are allergic to one or some of the drugs and there are others you might be able to have. Your doctor will know this. 
  • Your cancer cells have a lot of repeated changes in the DNA Open a glossary item. This is called microsatellite instability Open a glossary item high (MSI-H). Your doctor will know this. 
  • Your cancer cells have a lack of gene changes that help fix DNA when it is copied. This is called mismatch repair deficient Open a glossary item (MMRd). Your doctor will know this.  
  • You have surgery within 4 weeks of randomisation Open a glossary item.
  • You have radiotherapy within 7 days of randomisation. 
  • You have certain heart problems Open a glossary item and lung problems Open a glossary item.
  • You have tinnitus Open a glossary item or hearing loss from having cisplatin. 
  • You are having phenytoin and you can’t change it for another similar medication. 
  • You have active hepatitis B, active hepatitis C or HIV.
  • You have an immune system Open a glossary item that is not working well.
  • You had an experimental drug or used a device as part of another clinical trial within 30 days of joining the trial.
  • You are pregnant or breastfeeding.
  • You have any other medical conditions, mental health conditions or other circumstances that might affect you taking part in the trial. 

There are other entry conditions which mean you might not be able to take part. These have to do with the treatments. Your doctor will know about them.

Trial design

This is a European phase 3 trial

Everyone will have 4 cycles of standard treatment. The standard treatment is either:

  • gemcitabine and cisplatin (GemCis) or 
  • GemCis with durvalumab

Your doctor will tell you which one you will have. 

Gemcitabine and cisplatin are chemotherapy drugs. You have them as a drip into a vein. Durvalumab is an immunotherapy. You have it as a drip into a vein.

You have treatment in cycles. Each treatment cycle Open a glossary item is 3 weeks. You have gemcitabine and cisplatin at the start of weeks 1 and 2. You have durvalumab at the start of week 3. 

There are 2 parts to this trial. The first part is the screening part. The second part is the randomised part. 

Screening part
The team need 800 people across Europe to join including 400 from the UK.

The team test the tissue sample of your cancer. This is to collect information about the cancer cells' genes. 

If your cancer cells have one or more of the gene differences, the team will ask if you want to join the randomised part of the trial. You don’t have to join the randomised part. 

If you don’t want to join the randomised part, or you don’t have any of the gene differences, the trial team will look at your medical notes for 1 year. This is to see:

  • whether you have any further treatment
  • what happens to your cancer 
  • how you are

Randomised part
The team need 159 people across Europe to join including 78 from the UK.

This is a randomised trial. A computer puts you into 1 of 6 groups. Neither you nor your doctor can choose which group you are in. The 6 groups are:

  • standard treatment
  • futibatinib 
  • ivosidenib
  • zanidatamab
  • neratinib and trastuzumab 
  • encorafenib and binimetinib 

Out of every 3 people, 1 person will go into the standard treatment group and 2 will go into one of the other groups.

Standard treatment
You have 4 more cycles of the standard treatment. If you are having durvalumab you continue having it as long as it is helping you and the side effects are not too bad. 

Futibatinib
You have futibatinib if you have a change in a gene called FGFR2. You have 4 more cycles of the standard treatment. You then have futibatinib. 

Futibatinib is a tablet. Your doctor will tell you how many tablets to take. You take them once day every day at the same time on an empty stomach. This means you should not eat or drink, apart from water, for 1 hour before taking the tablets and for 2 hours after. 

You continue taking futibatinib as long as it is helping you and the side effects are not too bad. 

Ivosidenib
You have ivosidenib if you have a change in a gene called IDH1. You have 4 more cycles of the standard treatment. You then have ivosidenib.

Ivosidenib is a tablet. Your doctor will tell you how many tablets to take. You take them once a day every day at the same time. You should not take ivosidenib with the following:

  • a meal high in fat
  • grapefruit
  • pomegranate 

These can affect how much ivosidenib your body absorbs. 

You continue taking ivosidenib as long as it is helping you and the side effects are not too bad.

Zanidatamab
You have zanidatamab if you have a change in a gene called HER2. You have 4 more cycles of the standard treatment. You then have zanidatamab. 

You have zanidatamab as a drip into a vein. You have it once every 3 weeks. You continue having zanidatamab as long as it is helping you and the side effects are not too bad. 
  
Neratinib and trastuzumab 
You have neratinib and trastuzumab if you have a change in a gene called HER2. You have 4 more cycles of the standard treatment. You then have neratinib and trastuzumab. 

Neratinib is a tablet. Your doctor will tell you how many tablets you take. You take neratinib once a day every day at the same time, preferably in the morning. You should not have grapefruit or pomegranate while having neratinib as this may make the possible side effects worse. 

You have trastuzumab as a drip into a vein. You have it every 3 weeks.

You continue having neratinib and trastuzumab as long as it is helping you and the side effects are not too bad. 

Encorafenib and binimetinib 
You have encorafenib and binimetinib if you have a change in a gene called BRAF. You have 4 more cycles of the standard treatment. You then have encorafenib and binimetinib. 

Encorafenib is a capsule. Your doctor will tell you how many capsules to take. You take encorafenib once a day every day in the morning. You should not have grapefruit or pomegranate while having encorafenib as this may make the possible side effects worse. 

Binimetinib is a tablet. Your doctor will tell you how many tablets to take. You take binimetinib twice a day every day. You have the first dose in the morning with encorafenib and the second dose in the evening. 

You continue having encorafenib and binimetinib as long as it is helping you and the side effects are not too bad. 

Patient diary
You fill in a diary which you must bring with you to all your hospital appointments. In the diary you record:

  • side effects and symptoms
  • other medication you are taking, whether it is over the counter or prescribed

Your doctor will tell you more about what information to put in the diary. 

Samples for research
The team take blood samples at the start of the trial, during the trial and at the end. Your doctor can tell you more about how often they take these blood samples. Where possible they will take these samples when you have blood taken as part of your routine care. 

The team will ask for a sample of tissue (biopsy Open a glossary item) at the start of the trial, at the end of the trial and if your cancer gets worse. You don’t have to agree to have these tissue samples taken. You can still take part in the trial. 

Quality of life 
During the randomisation part you fill in questionnaires at the start, during and at the end. The questions ask about:

  • your general health and wellbeing
  • your daily activities
  • any side effects

These are quality of life questionnaires

Hospital visits

Screening part
You see the doctor to have blood tests and a CT scan or an MRI scan. Your doctor will tell you which scan you have.

Randomisation part
You see the doctor for tests before taking part. These tests include:

You see the doctor regularly during treatment for blood tests and to see how you are. You might also have regular tests during treatment. Which tests depends on the treatment you are having. Your doctor can tell you more about this. 

You have a scan every 9 weeks until your cancer starts to grow again. 

Follow up
You see the doctor about a month after finishing treatment. This is to see how you are and for the same tests you had at the start. 

You then see the doctor every 12 weeks for at least 1 year.

Side effects

The trial 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.

Durvalumab can affect the immune system Open a glossary item. This may cause inflammation Open a glossary item and other reactions in different parts of the body. For many people the inflammation and reactions are not too bad. For some people they can cause serious side effects. 

These side effects could happen during treatment or months after treatment has finished. Rarely, these side effects could be life threatening. Your doctor or nurse can explain what these side effects are, the risk of them happening and what to look out for.
 
If you have any of these side effects tell your doctor or nurse as soon as possible. You should tell them that you are on or have been on an immunotherapy.

 

Futibatinib
The most common side effects of futibatinib include:

Ivosidenib 
The most common side effects of ivosidenib include:

Ivosidenib can cause heart problems. You have regular heart tests while having treatment. 

Ivosidenib can also cause a rapid increase in cells of the immune system Open a glossary item. This is called differentiation syndrome, and it can be life threatening. Some symptoms include:

  • feeling sick
  • low blood pressure causing dizziness and feeling faint
  • high temperature (fever)
  • shortness of breath
  • weight gain
  • swelling of the hands and feet
  • difficulty passing urine

Contact your doctor straight away if you have these symptoms.  

Zanidatamab
The most common side effects of zanidatamab include:

  • diarrhoea
  • a reaction while having zanidatamab, signs can include fever, chills, fast heart rate, headache, hives, skin rash, difficulty breathing, sore throat, feeling or being sick, swelling and difficulty swallowing. Tell your nurse straight away if you have any of these signs. Your nurse will watch for signs of a reaction while you are having zanidatamab. 

Neratinib
The most common side effects of neratinib include:

Trastuzumab 
The most common side effect of trastuzumab include:

  • a reaction while having trastuzumab or in the next few hours after, signs can include fever, chills, fast heart rate, headache, hives, skin rash, difficulty breathing, feeling or being sick, swelling of lips and face, tiredness and dizziness. Tell your nurse straight away if you have any of these signs. Your nurse will watch for signs of a reaction while you are having trastuzumab. 
  • infections
  • diarrhoea or constipation
  • heartburn
  • tiredness (fatigue)
  • skin rash
  • chest, tummy (abdominal), muscle and joint pain
  • a drop in red blood cells that can cause tiredness and breathlessness
  • eye problems such as watery eyes and conjunctivitis 
  • nosebleeds and a runny nose
  • hair loss
  • trembling and shaking 
  • hot flushes Open a glossary item

Trastuzumab can also affect the heart. You have regular heart tests while having trastuzumab.

Trastuzumab can also cause changes to the levels of chemicals in your blood due to the breakdown of tumour cells (tumour lysis syndrome). You have regular blood tests to check for this.

Encorafenib and binimetinib 
The most common side effects of having encorafenib and binimetinib include:

  • a drop in the red blood cells that can cause tiredness and breathlessness
  • nerve problems such as pain, numbness and tingling in the hands and feet
  • headache
  • dizziness
  • bleeding in various parts of the body
  • high blood pressure
  • problems with your eyesight
  • stomach, joint, back, arms and legs pain
  • diarrhoea or constipation
  • feeling or being sick
  • skin problems such as itching, dry skin, skin rashes and thickening of the skin
  • thinning or loss of hair
  • high temperature (fever)
  • swelling of the hands, feet and other areas of the body
  • tiredness (fatigue)
  • changes to how the liver works
  • a rise in an enzyme in the blood that may show inflammation of the muscle or muscle damage

We have more information about:

We have information about:

Your doctor will talk to you about the possible side effects of all treatments in the trial and answer any questions you may have before you agree to take part.

Location

Belfast
Bristol
Cambridge
Cottingham
London
Maidstone
Manchester
Northwood
Norwich
Nottingham
Oxford
Peterborough
Sheffield
Southampton
Swansea
Wirral

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.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Dr John Bridgewater

Supported by

Cancer Research UK
UNICANCER
Cancer Research UK & UCL Cancer Trials Centre
Belgian Group of Digestive Oncology (BGDO)

Other information

CRUK/21/015

If you have questions about the trial please contact our cancer information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

19939

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Last reviewed:

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