A trial comparing lenvatinib and sorafenib for primary liver cancer

Please note - this trial is no longer recruiting patients. We hope to add results when they are available.

Cancer type:

Liver cancer

Status:

Closed

Phase:

Phase 3

This trial is comparing an experimental drug called lenvatinib with an approved drug called sorafenib for people with a type of primary liver cancer called hepatocellular carcinoma.

Doctors use a number of different treatments for hepatocellular carcinoma (HCC). If it is not possible to remove the cancer with surgery, one treatment your doctor may recommend is sorafenib. This is a standard treatment for some people with advanced HCC.

Lenvatinib (previously known as E7080) targets certain proteins on cancer cells or on blood vessels including receptors for vascular endothelial growth factor (VEGF).

VEGF helps cancers to grow blood vessels, so they can get food and oxygen from the blood. All cancers need a blood supply to be able to survive and grow. Lenvatinib blocks the receptor for this protein, stopping VEGF binding to it. This prevents the cancer from developing new blood vessels and hopefully stops the cancer from growing.

Lenvatinib has been looked at in trials in other types of cancer including thyroid cancer, and in an earlier small study for people with HCC. The researchers now want to compare lenvatinib with sorafenib.

The main aims of this trial are to find out

Whether lenvatinib or sorafenib is better at treating HCC
Learn more about the side effects of each treatment

Who can enter

You may be able to join this trial if all of the following apply.

You have hepatocellular carcinoma (HCC) that cannot be removed with surgery
Your cancer can be accurately measured on a scan and meets the minimum size requirements (the trial team can advise you about this)
If you have had radiotherapy or another treatment directly to liver, a scan must be able to show that your cancer has grown despite this treatment
You have stage B or C hepatocellular carcinoma and your liver is working normally (Child-Pugh score A)
You have satisfactory blood test results
You are willing to use reliable contraception during treatment and for 4 weeks before and after treatment if there is any chance that you or your partner could become pregnant
You are well enough to carry out all your normal activities such as light housework, but may not be able to carry out heavy physical work (performance status of 0 or 1)
You are at least 18 years old

You cannot join this trial if a scan has shown that your HCC

Is in over half of your liver
Has spread into the bile duct
Has grown into a major branch of one of the main blood vessels (the main portal vein)

And as well as the above, you cannot join if any of these apply. You

Have cancer that has spread to your brain
Have had a liver transplant
Have had major surgery in the last 3 weeks, or you are due to have surgery
Have had anticancer treatments that reach your whole body (systemic treatment ) for advanced HCC, including chemotherapy, any treatment targeting the receptors for vascular endothelial growth factor (VEGF), or treatment in a trial
Have had treatment directly to the liver, such as chemoembolisation or radiofrequency ablation in the last 4 weeks
Have had a blood transfusion , other blood products, erythropoietin or a growth factor such as G-CSF in the last 4 weeks
Are still having side effects from any anti cancer treatment, apart from hair loss and infertility
Have certain heart problems (the trial team can advise you about this)
Have had any other cancer in the last 3 years apart from carcinoma in situ of the cervix or non melanoma skin cancer that was successfully treated
Are known to be HIV positive
Are allergic to the drugs used in this trial, anything they contain, or to similar drugs
Have any other medical condition that the trial doctor thinks could affect your taking part

Trial design

This is an international phase 3 trial. The researchers need 940 people to join worldwide.

It is a randomised trial. The people taking part are put into treatment groups by a computer. Neither you nor your doctor can decide which group you are in. But you will both know which treatment you are having.

People in one group have lenvatinib
People in the other group have sorafenib

Trial diagram

Whichever drug you have, you take it by mouth. If you have lenvatinib, you take 2 or 3 capsules once a day depending on your body weight. The trial team will tell you how many capsules you need to take. You cannot take certain medicines during the research study. This includes aspirin (at any dose) and any medicines that contain aspirin.

If you have sorafenib, you take 2 tablets twice a day.

Whichever group you are in, you have treatment for as long as it is helping you and you don't have bad side effects.

The trial team will monitor you closely during treatment. If you have bad side effects, your doctor may stop your treatment for a while, lower the dose of the drug, or stop your treatment permanently.

They will ask you to fill out 3 questionnaires before you start treatment, every 4 weeks during treatment and after you finish treatment. These questionnaires will ask about side effects and how you’ve been feeling. This is called a quality of life study.

Hospital visits

You see the doctors and have some tests to decide whether you can take part in this trial. The tests include

Blood tests
Physical examination
Endoscopy to look at the inside of your food pipe (oesophagus) and stomach
Heart trace (ECG )
Heart scan (echocardiogram ) or MUGA scan
Urine test
CT scan or MRI scan, or both
Tests to see how well your liver is working (Child-Pugh score tests)

You may have some of these tests again before you start treatment.

You go to hospital about every 2 weeks during treatment. A trial doctor will also telephone you a week after you start treatment, to check how you are.

At these 2 weekly appointments, your doctor will ask you how you are and about any side effects you are having. Your tests will include

Blood tests
Heart trace (ECG)
Tests to see how well your liver is working (Child-Pugh score tests)
Urine test

If you have lenvatinib, you will need to have some extra blood tests that the group taking sorafenib will not have. So every 4 weeks, you have an extra blood test before and after taking lenvatinib.

Every 2 months you have

A CT scan of your chest
A CT scan or MRI scan of your stomach and pelvis

You have a scan again when you finish treatment (unless you have had one in the last 4 weeks).

After you finish treatment, you will see the doctors every 3 months. Or if this is not possible, the trial team may telephone you to ask how you are. You may have some further scans.

Side effects

As lenvatinib is a new drug, there may be side effects we don’t know about yet. The most common side effects we do know about include

High blood pressure (hypertension)
Tiredness (fatigue)
Diarrhoea
Feeling or being sick
Protein in your urine (proteinuria), the trial team will test your urine regularly and if it contains protein you will need to do a 24 hour urine collection to check your kidneys are working normally
Loss of appetite and weight loss
Hoarse voice
Tummy (abdominal) pain
Sore or dry mouth or throat
Headache
Constipation
Neck or back pain
Soreness, redness and peeling on the palms of the hands and soles of the feet (hand-foot syndrome), which may cause tingling, numbness, pain and dryness
Skin rash
A drop in the number of platelets causing an increased risk of bruising and bleeding problems
Pain in your bones, muscles or joints
Feeling generally weak
Changes to the way your thyroid gland works
Shortness of breath
Swelling in your arms or legs due to a build up of fluid
Indigestion
Dizziness
Rash or dry skin
Changes to your sense of taste
A cold or a urine infection
Problems sleeping

The most common side effects of sorafenib include

Diarrhoea
Feeling or being sick
Tiredness (fatigue)
Pain (this may be headaches, mouth pain, abdominal pain, bone pain or pain where you cancer is)
Hair loss
Flushing of the skin
Soreness, redness and peeling on the palms of the hands and soles of the feet (hand-foot syndrome), which may cause tingling, numbness, pain and dryness
A rash or red dry itchy skin
A drop in the number of platelets causing an increased risk of bruising and bleeding problems
High blood pressure