A study of MIV-818 for liver cancer

Cancer type:

Liver cancer
Secondary cancers

Status:

Open

Phase:

Phase 1/2

This study is looking at MIV-818 in combination with lenvatinib or pembrolizumab for people with advanced liver cancer. Open a glossary item

More about this trial

Lenvatinib is a targeted drug Open a glossary item called a cancer growth blocker. It works by stopping signals that tell cancer cells to grow. It also stops the cancer forming new blood vessels. Cancer cells need blood vessels to keep growing. 

Doctors already use lenvatinib to treat liver cancer

Pembrolizumab is an immunotherapy. It works by stimulating the immune system Open a glossary item to fight cancer cells. 

In the UK doctors don’t use pembrolizumab to treat liver cancer. But research shows that pembrolizumab might help people with liver cancer. 

MIV-818 is a prodrug. In the body it is changed to a drug that works in the same way as chemotherapy. So, it works by affecting the DNA  Open a glossary itemof the cancer cells. Studies done in the laboratory show that MIV-818 might help people with liver cancer. 

This study has 2 stages. In the first stage the team found the best dose of MIV-818 to have by itself. The best dose is the highest dose with the fewest side effects. 

The first stage has finished. The team found the best dose of MIV-818 to have by itself.

In the second stage you have MIV-818 with lenvatinib or pembrolizumab. It is your doctor’s decision whether you have lenvatinib or pembrolizumab. 

The aims of this study are to find:

  • the best dose of MIV-818 to have by itself. This is now completed and the team have found the best dose.
  • the best dose of MIV-818 to have with lenvatinib and pembrolizumab
  • out about the side effects of having MIV-818 with lenvatinib and pembrolizumab
  • whether these treatment combinations can help people with liver cancer

Who can enter

The following bullet points are a summary of the entry conditions for this study. Talk to your doctor or the study 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 study if all of the following apply. 

  • You have a type of liver cancer called hepatocellular carcinoma that has spread and cannot be removed by surgery. Or that cannot be treated with thermal ablation (RFA or MWA) and trans arterial chemoembolisation (TACE).
  • Your doctor is considering treating you with lenvatinib or pembrolizumab.
  • Your liver is working normally.
  • You are able to look after yourself but might not be able to do heavy physical work (performance status 0 or 1). 
  • You have an area of cancer the doctor can measure.
  • You have satisfactory blood test results.
  • You are willing to use contraception during treatment and for a time after. This is if you or your partner could become pregnant. 
  • You are at least 18 years old. 

Who can’t take part

Cancer related
You cannot join this study if any of these apply. You have:

  • another type of liver cancer that isn’t hepatocellular carcinoma. This includes if it is a mixed type. 
  • have had more than 2 courses of treatment Open a glossary item for your advanced liver cancer
  • cancer in more than half (50%) of the liver 
  • cancer spread to the brain or spinal cord. You might be able to join if it has been treated and stable for at least 3 months. 
  • had another cancer within the past 2 years. This is apart from non melanoma skin cancer Open a glossary item and a carcinoma in situ.  Open a glossary item
  • another cancer treatment within 4 weeks of starting the trial treatment 
  • ongoing moderate to severe side effects of previous treatment. This is apart from hair loss. 

Medical conditions
You cannot join this study if any of these apply. You:

  • have had an organ transplant Open a glossary item or a bone marrow transplant Open a glossary item
  • are taking medication that damps down the immune system Open a glossary item. This is apart from a small dose of steroids. Your doctor will know how much this is.
  • have HIV, hepatitis B, hepatitis C or tuberculosis (TB). You have another active infection that needs systemic treatment Open a glossary item such as antibiotics.
  • have fluid around the abdomen (ascites) that is not well controlled or that needs to be drained often. Your doctor will know how often this is. 
  • have problems with your brain such as confusion and drowsiness (encephalopathy) within 6 months before joining the trial. You cannot join if you are taking medication for encephalopathy. 
  • have bleeding from your food pipe (oesophagus) within 2 weeks of joining the trial. If you are having pembrolizumab it is 12 weeks.
  • are taking an experimental drug or have taken an experimental drug within 4 weeks of joining the trial
  • are taking medication including herbal products that affect the CYP3A4 enzymes. This unless your medication can be changed for another that doesn’t affect these enzymes. Your doctor will know what medications affect these enzymes and if they can be changed. 
  • have high blood pressure
  • have a problem with bleeding or are taking medication that thins the blood
  • are willing to have a heart trace (ECG Open a glossary item) and the results show a long QTc wave. Your doctor will arrange the ECG and will tell you the results.
  • have an active autoimmune disease Open a glossary item and you have had systemic treatment for it in the past 2 years. This is apart from treatment that replaces something the body makes. An example is hormone replacement Open a glossary item
  • have inflammation of the lungs that isn’t caused by an infection or you have had treatment for this in the past
  • have an increased amount of protein in your urine. Your doctor will test for this. 
  • have any other medical condition or mental health problem that could affect you taking part

Other
You cannot join this study if any of these apply. You:

  • are allergic or sensitive to any of the treatments used 
  • have a live vaccine Open a glossary item within 30 days of starting treatment. The COVID-19 vaccines aren’t live vaccines. 
  • are pregnant or breastfeeding

Trial design

This is an international phase 1/2 study. There are 2 stages in the study. 

In the first stage the team found the best dose of MIV-818 to have by itself. The best dose is the highest with the fewest side effects. This stage is now completed. 

In the second stage the team want to find the best dose of MIV-818 to have with lenvatinib. And also the best dose of MIV-818 to have with pembrolizumab. 

For this stage they need up to 66 people to join worldwide.

After talking to you the doctor decides whether you have lenvatinib or pembrolizumab.

You have treatment in cycles Open a glossary item. Each treatment cycle is 21 days.  

MIV-818 are capsules. You take them once a day for the first 5 days of each treatment cycle. You take them in the morning without food or after a light breakfast. 

You have a diary to fill in when you take MIV-818. You must bring this with you when you go to the hospital for your clinic appointments. 

Lenvatinib are capsules. You take them every day during the treatment cycle. 

You have pembrolizumab as a drip into a vein. You have it once at the start of the treatment cycle. You have it at the hospital and it takes about 30 minutes. 

You continue with treatment as long as it is helping and the side effects aren’t too bad. 

Samples for research
You give several blood samples for research during the study. Where possible the team take these samples when you have blood taken for routine blood tests. The team will tell you how many and how often they will take these samples.

The team take a sample of liver tissue (biopsy Open a glossary item) during treatment. They will tell you when they want to take the sample. 

They will ask for another tissue sample further on in treatment. This sample is optional you don’t have to agree to have it taken. 

Researchers will use these blood and tissue samples to find:

  • out what happens to the treatment in the body
  • out how the treatments affect the body
  • substances in the blood (biomarkers Open a glossary item) that might tell how well treatment is working
  • out more about liver cancer

Hospital visits

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

  • a physical examination Open a glossary item 
  • blood tests
  • urine test
  • heart trace (ECG Open a glossary item)
  • CT scan
  • MRI scan

You see the doctor regularly during treatment for blood tests and to see how you are.

You have a CT scan and MRI scan every 6 weeks while having treatment. 

A month after you stop taking MIV-818 you see the doctor for:

  • a physical examination
  • blood tests
  • heart trace

You then see the doctor as part of the study at 3 months and 6 months. They will then tell you how often they want to see you.

Side effects

The study 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.

Pembrolizumab can affect the immune system. It may cause inflammation in different parts of the body. This can cause serious side effects. They could happen during treatment, or some 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.

 

MIV-818 is a new drug. So there may be side effects we don’t know about yet. 

A very few people have had MIV-818. Some of the side effects reported included:

We have information about and the side effects of:

Your doctor will talk to you about the treatments and their side effects before you agree to take part.

Location

Glasgow
London
Newcastle upon Tyne

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

Professor Ruth Plummer

Supported by

Medivir

Freephone 0808 800 4040

Last review date

CRUK internal database number:

16921

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

Charlie took part in a trial to try new treatments

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“I think it’s really important that people keep signing up to these type of trials to push research forward.”

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