A study looking at a drug called ADP-A2AFP (AFPc332T) for 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 1

A study to find out how safe a drug called ADP-A2AFP is for liver cancer and how well it works.

It is open to people who have a primary Open a glossary item liver cancer that has got worse after treatment.

More about this trial

In this study researchers are looking at using changed T cells Open a glossary item from your own body to treat cancer. T cells are a part of your immune system . They help fight diseases including cancer.

The study team take some T cells from your blood and change them in the lab. They change the genes Open a glossary item of the T cells so that they can better recognise and fight cancer. The changed T cells are then called ADP-A2AFP.

You then have ADP-A2AFP as a drip into a vein or through a central line.

The main aims of this study are to find out:

how safe it is to have ADP-A2AFP
how well people tolerate having ADP-A2AFP
how well it works
what happens to it in the body
what the side effects are

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 advanced hepatocellular type of liver cancer that can’t be treated with a liver transplant, surgery or another procedure to reduce the size of the cancer
have a human leukocyte antigen (HLA ) type that could work with the changed T cells
have cancer that the doctor can measure
have cancer that has got worse after standard treatment or you can’t have standard treatment or don’t want standard treatment
have a sample of cancer tissue (biopsy ) available that has a high level of AFP
have a sample of non cancer tissue (biopsy) available that does not have a high level of AFP
have a score of 6 or less on the Child-Pugh staging. Your doctor will work out what your score is.
can look after yourself and do your normal activities but might not be able to do heavy physical work (performance status 0 or 1)
have satisfactory blood test results
are willing to use contraception during the study and for a time after if you or your partner could become pregnant
are at least 18 years old and no older than 75 years

Who can’t take part

Cancer related

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

have had certain cancer treatments for different periods of time before starting the study treatment. Your doctor will know which treatment and for how long.
have cancer spread to the brain
have moderate to severe ongoing side effects from previous treatment
have had another cancer within the past 3 years apart from successfully treated non melanoma skin cancer or an in situ carcinoma

Medical conditions

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

have had a liver transplant
have had major surgery within 4 weeks of starting treatment or you have not fully recovered from surgery
have had moderate to severe bleeding within the 3 months before starting treatment
have fluid on the tummy (abdomen) that needs treatment
have an enlarged liver
have active infection of the liver (hepatitis)
have HIV, HTLV1 or HTLV2
have an ongoing (chronic) autoimmune disease or one that has come back in the past year and you are taking medication such as steroids that damp down the immune system
have had a heart attack or angina in the past 6 months or have other heart problems
have a lung disease and need to use oxygen
have had a stroke in the past 6 months
have a problem with alcohol or drugs
have any other medical condition or mental health problem that your doctor or the study team think could affect you taking part

Other

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

are allergic to the treatments used in the study or any of their ingredients
are pregnant or breastfeeding

Trial design

This is a phase 1 study. The study team need up to 45 people to take part. There are 2 parts to this study.

In the first part the first few people taking part have a small dose of ADP-A2AFP. If they don’t have any serious side effects the next few have a larger dose. And so on until they get the best dose. This is called a dose escalation study.

In the second part everyone has the best dose of ADP-A2AFP. This is a dose expansion study.

There are 4 steps to this treatment:

collecting the T cells (leukapheresis)
processing the T cells to make ADP-A2AFP
chemotherapy before having ADP-A2AFP
having ADP-A2AFP

Diagram 1

Collecting the T cells
You have a thin tube (cannula Open a glossary item ) in your vein or a long line such as a central line . This is connected to a machine where your blood goes through. The machine filters out certain blood cells and everything else goes back into your bloodstream. It can take up to 4 or 5 hours.

The T cells are then separated from the collected blood cells and sent to the lab.

Making ADP-A2AFP
In the lab your T cells are changed into ADP-A2AFP. This takes about a month.

It is possible the lab staff might not be able to change your T cells. In this case your doctor will talk about the options available. One option might be you have another blood collection done.

Chemotherapy before ADP-A2AFP
You have chemotherapy during the week before ADP-A2AFP. You have:

You have them as a drip into a vein or through a central line. You have chemotherapy for 3 or 4 days.

The day after you finish your chemotherapy you have G-CSF. You have this as an injection under the skin.

You can have chemotherapy as an inpatient in the hospital or as a day patient in the outpatient department. Your doctor will talk to you about this and you both can decide which is best.

Having ADP-A2AFP
The ADP-A2AFP you have is made from your own T cells only.

You have your ADP-A2AFP as an inpatient in the hospital. You have ADP-A2AFP 4 or 5 days after the chemotherapy. You have it as a drip into the vein or through a central line. This takes about 15 to 30 minutes.

Before having ADP-A2AFP you have an antihistamine Open a glossary item and paracetamol to help with certain side effects. A member of the study watches you closely for 4 to 8 hours after having ADP-A2AFP for any side effects.

Research samples
You give blood samples at certain times during the study. The team use these to find out how your body is reacting to ADP-A2AFP and how it affects your body. They are also looking at how it affects substances in the blood (biomarkers Open a glossary item ).

You give 3 tissue samples (biopsies Open a glossary item ) from your cancer after having ADP-A2AFP. Your doctor will explain this to you. The team use these samples to help understand:

the cancer and how it affects ADP-A2AFP
how the cancer cells might have changed after ADP-A2AFP
which biomarkers might have changed and might show that the cancer is getting worse or might return
if there are cells from the immune system in the cancer and what are they doing

Hospital visits

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

a physical examination
blood tests
heart trace (ECG )
heart scan (ECHO or MUGA)
CT scan or MRI scan

You see the doctor before having your T cells collected (leukapheresis) to see how you are.

In the week before starting chemotherapy you see the doctor for:

a physical examination
heart scan
CT scan or MRI scan
blood tests

During chemotherapy you see the doctor each day to see how you are.

Before having ADP-A2AFP you have a heart scan and physical examination.

After leaving the hospital you see the doctor several times in the first 6 months. You then see them every 3 months till the end of the study or your cancer starts to get worse.

You have a CT scan or MRI scan at:

4 weeks
8 weeks
16 weeks
24 weeks and then
every 3 months

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.

ADP-A2AFP is a new drug and there may be side effects we don’t know about yet. Side effects that have occurred in people who had changed T cells like ADP-A2AFP include some that you should contact your doctor straight away if you have any of them. They include:

cytokines release syndrome, this is a group of symptoms caused by the release of chemicals from other cells after having changed T cells. The symptoms are flu-like such as fever, feeling lightheaded, feeling sick, headache, confusion, rapid heartbeat, shortness of breath and a rash. In most cases your team can easily manage them but they can be life threatening.
encephalopathy syndrome, a brain condition that changes how you think including difficulty paying attention, difficulty with talking or writing, feeling confused or agitated, difficulty sleeping and the shakes (tremors). Doctors can treat this but it is serious and life threatening.
a drop in blood cells that can cause shortness of breath, tiredness, an increased risk of infection, bruising and bleeding
graft versus host disease (GvHD) where your immune system attacks healthy tissue and cells. Symptoms include a rash, blisters, stomach pain, peeling skin, feeling or being sick and diarrhoea. Doctors can treat GvHD but it can be serious and life threatening. You need to contact or see your doctor straight away if you have any of these symptoms.