A trial looking at combining two treatments for cancer of the liver - TACE 2

This trial is looking at combining a drug called sorafenib with another type of treatment called chemoembolisation to treat cancer that started in the liver (primary liver cancer).

Doctors use different treatments for liver cancer. One is by blocking the supply of oxygen and food that the cancer needs to grow. Doctors can do this by injecting small beads into the blood vessels near the cancer. The aim is to block the small blood vessels (embolisation). The beads can also deliver chemotherapy directly to the cancer. This is called chemoembolisation. Transarterial chemoembolisation (TACE) is a type of chemoembolisation used for liver cancer.

Sorafenib is a biological therapy called a tyrosine kinase inhibitor. Tyrosine kinase is a chemical messenger (an enzyme) that signals cancer cells to grow. Sorafenib blocks these signals.

Sorafenib can also work by blocking the growth of new blood vessels that supply the cancer with food and oxygen.

Researchers think that combining sorafenib with TACE may be better than TACE alone for treating liver cancer that cannot be removed by surgery.

The aims of this trial are to find out

If combining sorafenib with TACE is better than TACE alone
What are the side effects of combining sorafenib with TACE
How this combination affects quality of life

Recruitment

Start 19/11/2010

End 30/11/2013

Phase

Phase 3

Who can enter

You can enter this trial if you

Have at least one area of primary cancer of the liver that can be seen on a scan
Have satisfactory blood test results
Have satisfactory heart test results
Are fully active and can do anything you would normally do, apart from heavy physical work (performance status 0, 1)
Are willing to use reliable contraception during treatment and for 3 months after if there is a chance you or your partner could become pregnant
Are at least 18 years old

You cannot enter this trial if you

Are able to have surgery to remove your cancer or liver transplant surgery
Have cancer that has spread outside your liver (stage 4)
Have already had treatment for your cancer, including radiotherapy, chemotherapy or beads put in to block the blood supply to the cancer (embolisation)
Have severe liver cirrhosis
Have fluid collected in your tummy (abdomen) that cannot be controlled by medication (doctors call this ‘ascites’)
Had problems with bleeding in the past 4 weeks
Have an infection
Are HIV positive
Are pregnant or breastfeeding

Trial design

This is a phase 3 trial. It will recruit 412 people throughout Europe. It is a randomised trial. You will be put into 1 of 2 treatment groups. Neither you nor your doctor can choose which group you are in or will know which group you are in. This is called a double blind trial.

If you are in group 1, you will have TACE and sorafenib.

If you are in group 2, you will have TACE and a dummy drug (placebo).

The beads used in this trial for TACE contain the chemotherapy drug doxorubicin.

You go to the X-ray department to have the doxorubicin beads put in place. First you have a local anaesthetic injection into your groin to numb the area. The doctor puts a thin tube (catheter) into the largest blood vessel in your groin and threads it up to the artery that feeds the liver. Once they are sure that the catheter is in the right place, the doctors will inject the doxorubicin beads directly into your liver. The doctors will then remove the tube from your groin. The beads block the blood flow and deliver doxorubicin to the cancer.

Sorafenib and the dummy drug are tablets. You take them twice a day. You continue taking the tablets as long as they are helping you and the side effects are not too bad.

You will have a diary to write down when you take your tablets and any side effects you might have. You need to bring this with you every time you visit the hospital.

You will be asked to fill in a questionnaire

Before starting treatment
1 week after having the beads put in
Every 6 weeks while having treatment

The questionnaire will ask you about any side effects you have and how you have been feeling. This is called a quality of life study. If you don’t want to take part in this study you don’t have to. You can still take part in the trial.

Hospital visits

You will see the doctor and have some tests before you take part in this trial. These tests include

A physical examination
Blood tests
Heart trace (ECG)
Heart scan (MUGA scan or echocardiogram)
CT scan or MRI scan

You see the doctor 1 week after having the beads put in and have the following tests

A physical examination
Blood tests

While on treatment you see the doctor every 6 weeks and have the following tests

A physical examination
Blood tests
CT scan or MRI scan – every other time

Side effects

The side effects of sorafenib can include

Redness, pain or swelling of the hands or feet
Numbness or tingling of the hands or feet
High blood pressure
Heart problems
Bleeding problems
Rash with red, itchy skin
Hair loss
Diarrhoea
Feeling or being sick
Mouth ulcers
Loss of appetite
Weakness and tiredness

You cannot take some medications while having sorafenib because they could affect how it works.

Your doctor will talk to you about which medications you cannot take.

The side effects of doxorubicin can include

Feeling, or being, sick
Tummy (abdominal) pain
Fever
A drop in the number of blood cells causing an increased risk of infection, bleeding and bruising
Tiredness and weakness

The side effects of having the beads put in (chemoembolisation) can include