A study looking at the SonoTran Platform for bowel cancer that has spread to the liver (CEeDD)

Cancer type:

Bowel (colorectal) cancer

Cancer spread to the liver

Secondary cancers

Status:

Open

Phase:

Other

This study is looking at using the SonoTran Platform in combination with chemotherapy and a targeted drug. It is for people whose bowel cancer has spread to the liver.

More about this trial

Doctors can treat bowel cancer spread with chemotherapy and a targeted cancer drug Open a glossary item . The chemotherapy drugs they can use include:

irinotecan
fluorouracil (5FU)
a combination of irinotecan, 5FU and folinic acid (FOLFIRI)

One of the targeted drugs they can use is cetuximab.

These drugs can help but researchers know that only a small amount of the drugs get into the cancer. So they are looking at ways to increase the amount of drugs that go into the cancer. They think that 2 new medical devices might help. The devices are designed to be used together. Together they are the SonoTran Platform.

The SonoTran Platform consists of the:

SonoTran System
SonoTran Particles

The SonoTran System is a specially designed ultrasound machine that is similar to an ultrasound scan Open a glossary item . It works by delivering special sound waves to a particular area of the body.

The SonoTran Particles are smaller than microscopic, cup shaped and have an air bubble inside the cup's cavity. When sound waves are directed at the particle the air bubble wobbles. The air bubble rapidly grows getting bigger until it bursts.

You have the SonoTran Particles as a drip into your vein. The doctor then uses the SonoTran System over the part of the body where the cancer is. The sound waves expand and shrink the SonoTran Particles. This rapid expanding and collapsing of the air bubbles can help pump more of the drugs into the cancer.

In this study researchers are looking at using the SonoTran Platform with irinotecan and 5FU (FOLFIRI) and cetuximab for bowel cancer that has spread to the liver.

There are 3 groups in this study. These are the:

Safety group. This group is now completed.
Performance group
Efficacy group

The main aims of this study are to find:

the dose of SonoTran Particles to use. The team found this out in the Safety group.
out how well the SonoTran Platform works for bowel cancer that has spread to the liver

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.

There are 3 groups in this study. The safety group has completed recruitment. There are some entry conditions that are the same for the performance group and efficacy group. And there are some entry conditions that are different for each group.

Who can take part

Everyone
You may be able to join this study if all of the following apply. You:

have bowel cancer that has spread to the liver
have at least 1 area of cancer spread in the liver that is bigger than 1cm across
have satisfactory blood test results
are willing to use contraception during the study and for a time after if there is any chance you or your partner could become pregnant
can look after yourself but might not be able to do heavy physical work (performance status 0 or 1)
are at least 18 years old

Performance group
You may be able to join group 2 if all of the following also apply.

Your doctor plans to remove your cancer spread to the liver by surgery.
You have had chemotherapy to treat your cancer spread. As long as it was completed at least 4 weeks before having the study treatment. And there is still some cancer left after the chemotherapy.
Your doctor plans to treat cancer spread to any other part of the body as part of the aim to cure.
Your cancer spread might or might not be in an area of the liver where the team can access it with the SonoTran. Your doctor will be able to tell you more about this.

Efficacy group
You may be able to join group 3 if all of the following also apply.

Your doctor does not plan to treat the cancer spread in the liver straight away either by surgery, by using radiofrequency ablation or microwave ablation (MWA).
You have at least 1 area of cancer in the liver that the team can access with the SonoTran.
Your bowel cancer does not have any changes (mutations ) in the RAS gene . Your doctor will know this.

Who can’t take part

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

have another cancer treatment within 4 weeks of the SonoTran treatment. For radiotherapy to the liver it is within 8 weeks.
have ongoing moderate to severe side effects from previous treatment that might affect you taking part. This is apart from certain side effects such as hair loss. Your doctor will know which side effects these are.
have not satisfactorily recovered from surgery within 4 weeks of joining the study
have an increased risk of bleeding or bruising
have an infection that needs treatment within 7 days of joining the study. You have HIV or cancer that is related to having HIV.
have taken part in another clinical trial within 4 weeks of joining this study
have an active inflammation of the bile duct
are pregnant or breastfeeding
have any other medical condition or mental health problem that could affect you taking part

Performance group
You cannot join the performance group if you have a gene change (mutation) of the UGT-1A1 gene.

Efficacy group

You cannot join the efficacy group if any of these also apply. You:

have a heart problem that could affect you taking part
have a low level or none of an enzyme called DPD . Or you have a gene change (mutation) of the UGT-1A1 gene.
can have surgery to remove the cancer spread in the liver straight away without first having any treatment to shrink it
have cancer spread in the liver that your doctor thinks is best treated with radiofrequency ablation or microwave ablation straight away

Trial design

There are 3 groups in this study.

Safety group
The safety group is now completed.

In this group the team found the amount of SonoTran Particles to give to use with the SonoTran System. They use this amount in the performance and efficacy groups.

Performance group
The study team needs 12 people to join the performance group.

You have an ultrasound Open a glossary item of your liver. This is to see where the cancer is in the liver. And to see whether the SonoTran can target the cancer spread. Depending on the results of the ultrasound you have either:

cetuximab and irinotecan or
cetuximab, irinotecan and SonoTran Platform

CEeDD trial Performance group randomisation diagram

You have cetuximab, irinotecan and SonoTran Particles as a drip into a vein. While having the SonoTran Particles the doctor uses the SonoTran System over the liver. This takes about 40 minutes.

You have this treatment the day before surgery to remove the cancer that has spread to the liver.

Efficacy group
The study team needs 24 people to join the efficacy group.

:You have an ultrasound Open a glossary item of your liver. This is to see where the cancer is in the liver. And to see whether the SonoTran can target the cancer spread. Depending on the results of the ultrasound you have either:

cetuximab and FOLFIRI
cetuximab, FOLFIRI and SonoTran Platform

CEeDD trial Efficacy group randomisation diagram

You have FOLFIRI as a drip into a vein. This takes about 5 hours.

You then have the SonoTran Particles as a drip into a vein. While having the SonoTran Particles the doctor uses the SonoTran System over the liver. This takes about 40 minutes.

You have the SonoTran Platform treatment every 2 weeks with the chemotherapy.

As a part of FOLFIRI you then have 5FU over 46 hours at home. For this you have a pump. After 46 hours you go back to the hospital to have the pump disconnected.

You have FOLFIRI every 2 weeks. Each 2 week period is a cycle of treatment Open a glossary item . You have 6 cycles of treatment as part of the study.

Samples for research
You give blood samples as part of the study. Where possible the team take these when you have blood tests taken as part of your routine care.

The team take tissue samples as part of the study. They take the samples from the parts of the liver that the surgeon removes during surgery.

They use these samples to see how SonoTran is working.

Not everyone has the blood samples and tissue samples taken. Your doctor will tell you if this applies to you. They will also tell you when and how often you have them.

Hospital visits

Performance and efficacy group
You see the doctor to have tests before taking part. These include:

a physical examination
blood tests
an ultrasound scan

You see the doctor at regular times during treatment. This is to see how you are and for blood tests.

Efficacy group
You have the following scans before treatment and twice more during treatment:

a CT scan
an MRI scan of the liver
a FDG PET-CT scan

Follow up for performance group
About 4 weeks after the start of the study you see the doctor. This is:

to see how you are
to ask about side effects
for a physical examination
for blood tests

Your doctor will then tell you how often they want to see you.

Follow up for efficacy group
About 2 weeks after you finish treatment you have:

a CT scan
an MRI scan of the liver
a FDG PET-CT scan

You then see the doctor 3 months later. This is:

to see how you are
to ask about side effects
for a physical examination
for blood tests

Your doctor 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.

The SonoTran Particles have not been used in people before this study. So the study team is still finding out what the side effects might be.

Based on animal studies possible side effects might include:

mild changes to the liver which might not cause symptoms. You have blood tests taken during the study to check how your liver is working.
inflammation or reaction in the vein where you have the SonoTran Particles. This might cause redness, soreness or a red line (tracking) along the vein.
mild redness on the skin where the ultrasound probe presses against it

What happens to the SonoTran Particles?
The SonoTran Particles enter your bloodstream and travel through your blood circulatory system. They may wobble for up to an hour if they are activated by an ultrasound wave. They may stay in the body for a long time but are inactive on their own.

Animal studies have shown that these particles are taken up by specialist cells in the liver and rest there. A small number may end up outside of the liver. But the particles should not cause any problems in other parts of your body.

The team doesn’t expect the SonoTran Particles to cause the side effects of the chemotherapy drugs to be worse.

We have information on the side effects of:

Your doctor will talk to you about the possible side effects of all the treatments used in the study. They will answer any questions you might have.