A study looking at a targeted treatment for glioblastoma (CITADEL-123)

Cancer type:

Brain (and spinal cord) tumours

Status:

Open

Phase:

Phase 1

This study is looking at a targeted treatment called 123I-ATT001 for a type of brain tumour called glioblastoma Open a glossary item that has come back after treatment.

More about this trial

Surgery is one of the treatments for glioblastoma that has come back. The aim of the surgery is to remove as much of the tumour as possible. This is called de bulking Open a glossary item surgery. After this you might have more treatment such as chemotherapy.

During your surgery, you might have a small plastic dome placed under the skin of your scalp. This is called an Ommaya reservoir. You can have chemotherapy and other treatments through the Ommaya reservoir. To do this, your doctor or nurse gently puts a small needle through your skin into the reservoir. The treatment goes through a thin tube into the tumour in your brain. It delivers treatment directly to the tumour.

123I-ATT001 is a targeted radionucleotide Open a glossary item therapy. It is made up of 2 parts. A delivery part and a treatment part. ATT001 is the delivery part. The treatment part is 123I.

ATT001 attaches to a certain protein in the tumour cells and delivers the 123I into the tumour cells. 123I is radioactive iodine. This damages and kills the tumour cells.

Doctors already use radioactive iodine to treat thyroid cancer.

Researchers want to find out if they can use 123I-ATT001 to treat glioblastoma. Before they can do this, they need to find out the best dose to give.

You have 123I-ATT01 into the Omaya reservoir.

The aims of this study are to find out:

more about the side effects of 123I-ATT001
the best dose to give that does not cause unacceptable side effects
how much 123I-ATT001 goes into the tumour and the healthy tissue of the brain
whether it goes to the rest of the body
whether it reduces the size of the tumour
whether it affects how well the brain and nerves work

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 glioblastoma that has an unchanged IDH gene (IDH wild type) that has come back after treatment (grade 4)
have had a scan that shows the glioblastoma has come back within the 3 months before starting the study treatment
can look after yourself, are up and about but might not be able to do heavy physical work (performance status 0 or 1)
have satisfactory blood test results
are willing to use reliable contraception during the study and for a time after if there is any chance you or your partner could become pregnant
are at least 18 years old

Who can’t take part

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

have had an experimental drug or used a device as part of a clinical trial, or study, within the 4 weeks before starting the study treatment. Or you are already in a clinical trial or study.
have an immune system that does not work well
are taking medication that damps down the immune system within the 7 days before starting the study treatment
have chemotherapy or a targeted drug to treat the glioma within the 4 weeks of agreeing to join the study
have radiotherapy or an immunotherapy to treat the glioma within the 4 weeks before starting the study treatment
have ongoing moderate to severe side effects from previous treatment apart from hair loss and those affecting the brain if they are stable and are linked to the glioma
are allergic to olaparib or iodine
have another cancer that needs active treatment. This is apart from successfully treated non melanoma skin and carcinoma in situ of the cervix.
are not able to have a SPECT scan or an MRI scan . This might be because you are not comfortable in confined spaces or you have metal implants in your body. Your doctor can tell you more about this.
have certain heart problems which your doctor will know
have an active infection that needs treatment that reaches your whole body (systemic treatment) such as an antibiotic
have had inflammation of the lungs (pneumonitis) that was not caused by an infection within the past 3 years
have a medical condition, mental health condition or any other circumstances that could affect you taking part
are pregnant or breastfeeding

Trial design

You have your surgery as planned. During surgery the surgeon puts in an Ommaya reservoir. You can take part if you have already had surgery as long as you are willing to have an Ommaya reservoir put in place. Your doctor will tell you about this.

You have 123I-ATT001 through the Ommaya reservoir.

This is a phase 1 study.

There are 2 parts to this study. Only part 1 is open to recruitment. When part 2 is open to recruitment we will update this summary.

The team need up to 21 people to join part 1.

The first few people taking part will have a low dose of 123I-ATT001. If these people don't have any serious side effects, the next few people will have a higher dose. And so on, until they find the best dose. This is called a dose escalation study Open a glossary item .

When you have recovered from surgery, you start having 123I-ATT001. You have it once a week. You have 4 treatments. After this, you might be able to have another 2 treatments. Your doctor will discuss this with you.

You might need to stay overnight in hospital after having treatment. Your doctor will tell you about this.

Samples for research
The team take blood samples. Where possible they take these when you have blood tests as part of your routine care.

They will use the samples to find out:

what happens to 123I-ATT001 in the body
how 123I-ATT001 affects the body

You must agree to have some of these blood samples taken. And some of the blood samples are optional. Your doctor or a member of the study team will tell you more about this.

During surgery the surgeon might take a sample of the fluid surrounding the brain and spinal cord (cerebrospinal fluid). The team will use this sample to look for substances (biomarkers Open a glossary item ) that might tell the how well treatment is working.

Hospital visits

You have your surgery, and the Ommaya reservoir put in. You then see the doctor for a physical examination Open a glossary item and tests. The tests include:

blood tests
a heart trace (ECG)
an MRI scan
a test to find out how well your brain and nerves are working, your doctor will ask you questions that will test your memory, thinking, hearing and eyesight

During treatment you see the doctor the day before and the day after each treatment. This is for tests and to see how you are.

Follow up
You see the doctor a month after finishing treatment. This is for tests and to see how you are. You then see the doctor every 2 months to 6 months.

You have an MRI scan every 8 to 10 weeks.

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.

123I-ATT001 is a new treatment for glioma. This is the first time it is been tested. So we don’t know what the side effects are.

As with all treatment 123I-ATT001 might affect the:

blood
kidneys
liver
heart

You have regular blood tests to check how well these are working.

It might also cause an allergic reaction. The signs and symptoms of this can include:

sneezing and an itchy, runny or blocked nose
itchy, red and watery eyes
wheezing, the chest feeling tight, shortness of breath and a cough
a raised, itchy, red rash (hives)
tummy (abdominal) pain, feeling sick, being sick or diarrhoea
dry, red, cracked skin

Some allergic reactions can be severe and life threatening. Signs and symptoms of this can include:

swelling of the throat and mouth
difficulty breathing
feeling lightheaded
confusion
blue skin or lips
fainting and losing consciousness

Contact your doctor straight away if you have any signs or symptoms of an allergic reaction.

During our everyday lives, we are exposed to low levels of radiation Open a glossary item from the environment, including the sun. This is called background radiation. 123I-ATT001 uses radiation to treat the cancer. It is a smaller amount of radiation than what you get from the background radiation. Most of the time, this amount of radiation is not harmful. It might increase your risk of getting another cancer later on. But the chances of this happening are very low.

Your doctor will tell you about 123I-ATT001 and answer any questions you might have before you agree to take part in the study.