A trial looking at brivanib and sorafenib for advanced liver cancer (The BRISK FL study)

Please note this trial is no longer recruiting patients.

This trial is comparing brivanib with sorafenib as treatment for a type of liver cancer called hepatocellular carcinoma (HCC).

Doctors can use different treatments for HCC such as liver resection or a liver transplant. Some treatments are directed just at the liver, such as radiofrequency ablation, percutaneous alcohol injection, chemoembolisation or cryotherapy. These are called ‘local’ treatments. Others are drugs that reach the whole body. These are called systemic treatments.

In this trial, researchers are looking at a new drug called brivanib, and a drug called sorafenib. Both are tyrosine kinase inhibitors. They work by stopping cancer cells forming new blood vessels (anti angiogenesis) and by blocking other signals that tell cancer cells to grow.

We know from research that sorafenib can help people with liver cancer. The aims of this trial are to

See if brivanib works as well as or better than sorafenib for people who have not had any other systemic treatment for advanced HCC
Compare how each drug affects quality of life

Recruitment

Start 16/03/2010

End 31/07/2011

Phase

Phase 3

Who can enter

You can enter this trial if you

Have advanced hepatocellular carcinoma (HCC) that cannot be removed with surgery or treated with other local treatments
Have at least one area of cancer that your doctors can measure and that has not already been treated with surgery, radiotherapy, or local treatments, including radiofrequency ablation, percutaneous alcohol injection, chemoembolisation or cryotherapy
Have satisfactory blood test results including liver function tests
Are well enough to take part and have a performance status of 0 or 1
Are willing to use reliable contraception during the trial and for at least 12 weeks afterwards if there is any chance you or your partner could become pregnant
Are at least 18 years old

You cannot enter this trial if you

Have cancer that has spread to your brain
Have a type of liver cancer called fibrolamellar HCC or a cancer that is a mixture of HCC and cholangiocarcinoma
Have HCC that is blocking a major blood vessel
Have had treatment directed at the liver in the last 3 weeks
Have already had chemotherapy or biological therapy for HCC
Have had radiotherapy in the last 4 weeks, apart from radiotherapy to treat symptoms (palliative radiotherapy)
Have had major surgery in the last 3 weeks or minor surgery such as a biopsy in the last week
Have already had another experimental drug for HCC
Have severe liver cirrhosis (Child-Pugh score of 7 or more)
Have had any change in your normal brain function due to illness (encephalopathy)
Have a build up of fluid in your abdomen (ascites)
Have hepatitis B that has not been treated
Have vomited blood in the last 6 months
Have had a drainage tube put in to reduce the blood pressure in your liver (a portal caval shunt)
Have had a heart attack in the last year
Have high blood pressure that cannot be controlled with medication, or a heart condition that is cause for concern
Have had a blood clot in the last 6 months or any serious bleeding in the last 2 months
Have an infection that cannot be controlled with medication
Have a problem with the way your thyroid gland works that cannot be controlled with medication
Have had an ulcer, a broken bone, or a wound that wouldn’t heal in the last 3 months
Have had an organ transplant or are currently on the waiting list to have a transplant
Have had any other cancer in the last 5 years apart from cervical cancer in situ, superficial bladder cancer, or basal cell skin cancer
Have any other medical condition that could affect you taking part in the trial
Are taking St John’s wort or a drug called rifampin
Take drugs to thin the blood (anticoagulants)
Cannot swallow or absorb tablets for any reason
Are known to be allergic to brivanib or sorafenib
Are known to be HIV positive
Are pregnant or breastfeeding

Trial design

This is an international trial that will recruit more than 1,000 people in different countries. It is a randomised trial. The people taking part will be put into treatment groups by a computer. Neither you nor your doctor can decide which group you are in. Everybody taking part will take tablets and capsules each day. Either the tablets or the capsules will be a dummy drug (placebo).

People in group A take brivanib once a day and dummy drugs twice a day
People in group B take sorafenib twice a day and a dummy drug once a day

As the dummy drugs look the same as the drugs being tested, neither you nor your doctor will know which group you are in. This is called a double blind trial.

You take the tablets and capsules at home, an hour before a meal, or 2 hours afterwards. If you don’t have any bad side effects, you can carry on having treatment for as long as it helps you.

You will be asked to complete a questionnaire at the beginning of the trial, every 3 weeks during treatment and when you finish treatment. The questionnaires will ask about any side effects you have had and about how you have been feeling. This is called a quality of life study.

To take part in this trial, the researchers will need to have a sample of your cancer. This can be from a biopsy that you had in the past. Or, if this is not available, they will ask you to have another biopsy before you start treatment. They will use the samples to try and find biomarkers. These are substances in the body that doctors can measure to help them see how a disease is developing or a treatment is working.

During the trial, the researchers will take some extra blood samples to look at what happens to the drugs in the body. This is called pharmacokinetics. They will also study how the drugs work and the effect they have on your body (pharmacodynamics).

Hospital visits

You will see the doctors and have some tests before you start treatment. The tests include

Physical examination
Heart trace (ECG)
Echocardiogram
CT scan or MRI scan
Blood and urine tests
A biopsy if there is not a sample of tissue available from an earlier biopsy

You go to hospital once a week for the first 3 weeks of treatment and then once every 3 weeks after that. You see the trial doctors and have blood tests each time. You have a scan every 6 weeks and an echocardiogram every 12 weeks during treatment.

After you finish treatment, a member of the trial team will contact you every 6 weeks to see how you are.

If you stop having the trial treatment for any reason other than your cancer getting worse, you will carry on having scans every 6 weeks until your cancer starts growing again.

Side effects

As brivanib is a new drug, there may be side effects that we don’t know about yet. From earlier trials, doctors know that the possible side effects include

Changes to liver enzymes
Tiredness (fatigue)
Raised blood pressure
Sickness
Diarrhoea
Loss of appetite and weight loss
Headache
A drop in the amount of salt (sodium) in your body which can affect how your nerves and muscles work or cause a build up of fluid