A trial looking at ABT-414 with radiotherapy and temozolomide for glioblastoma (Intellance 1)

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

Cancer type:

Brain (and spinal cord) tumours

Status:

Closed

Phase:

Phase 2/3

This trial is for people with a type of brain tumour called glioblastoma multiforme (GBM). It is for people whose GBM have a large number of copies of a gene. This gene makes a protein called epidermal growth factor. Open a glossary item

More about this trial

Surgery to remove as much of the brain tumour as possible is one of the standard treatments for GBM. This might be followed by a type of chemotherapy called temozolomide alongside radiotherapy (chemoradiation). These treatments can stop the growth of the tumour for a time, but it usually starts to grow again. Doctors want to improve the treatment for GBM.

An earlier trial has shown that ABT-414 can slow the growth of GBM. But this needs testing in a larger trial.
        
ABT-414 is a type of drug called an antibody drug conjugate (ADC). There are 2 parts to this drug. 

The first part targets cancer cells by attaching to a particular receptor on the surface of the cell. In the case of ABT-414, it attaches to the epidermal growth factor receptors (EGFR) on cancer cells.

The second part is a toxin that gets into the cancer cell and kills it. The toxin part of ABT-414 is called monomethylauristatin F (MMAF).  Once the antibody sticks to EGFR on the cancer cells, the MMAF is released and kills the cell.

In this trial everyone has standard treatment. Half will also have ABT-414 and the other half will have a dummy drug (placebo).  The aims of this trial are to

  • find out if ABT-414 is safe
  • learn more about the side effects of ABT-414 when given with temozolomide and radiotherapy
  • find out if ABT-414 and standard treatment is better than standard treatment alone

Who can enter

The following bullet points list the entry conditions for this trial. Talk to your doctor or the trial team if you are unsure about any of these. They will be able to advise you. 

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

  • You have glioblastoma multiforme (GBM) that has a large number of copies of a gene, which makes a protein called epidermal growth factor (the medical term for this is EGFR amplification)
  • You are able to care for yourself, even if you are not able to carry on with all your normal activities or do active work (Karnofsky performance of over 70)
  • You have satisfactory blood test results
  • You are willing to use reliable contraception during the trial and for 6 months afterwards if there is any chance that you or your partner could become pregnant
  • You are at least 18 years old

You cannot join this trial if any of these apply. 

  • You have GBM tumours in more than one place in your brain (mutifocal cancer)
  • Your GBM is affecting at least 3 lobes (parts) of the brain, this is called gliomatosis cerebri
  • Your GBM has come back (recurred) or has spread outside your brain for example, to your spinal cord
  • You have had any treatment apart from surgery for your GBM, you may still be able to take part if you were part of a study looking at the use of scans in cancer treatment 
  • You have not recovered from surgery to remove your GBM. For example your wound has not healed, you have not had your staples or sutures (stitches) removed or you have an infection 
  • You have had radiotherapy for a cancer of the head and neck area, except for early stage cancer of the glottis Open a glossary item 
  • You have had chemotherapy or a drug that makes a cancer more sensitive to radiotherapy for a cancer of the head and neck area. You might be able to take part if you have had chemotherapy for another type of cancer, as long as the chemotherapy was not temozolomide
  • You have had any other cancer in the last 2 years, unless it was a very early stage and has been successfully treated 
  • You have had a heart trace (ECG) in the last 3 weeks which shows that you have part or complete blockage of the blood supply to the heart (acute cardiac ischaemia)
  • You have had problems with heart failure in the last 6 months or you have needed to be admitted to hospital for heart failure in the last year
  • You have had angina that has been difficult to control in the last 6 months 
  • You have problems with an abnormal heart rhythm that is serious or cannot be controlled with treatment
  • You have had a heart attack in the last 6 months
  • You have had a stroke or mini stroke in the last 6 months
  • Your liver is not working properly (you have severe hepatic impairment with a Child-Pugh score of C or higher)
  • You have an infection which needs treatment with antibiotics into your vein
  • You have a lung condition such as chronic obstructive pulmonary disease
  • You have AIDS 
  • You have a connective tissue disorder such as lupus or scleroderma disease and your doctor thinks the radiotherapy will cause too severe side effects 
  • You have an eye condition which means you cannot have steroid eye drops
  • You are unable to have an MRI scan using a contrast dye
  • You have any other serious medical condition or mental health problem that the trial team think could affect you taking part
  • You have had eye laser surgery (LASIK) within the last year or cataract surgery within the last 3 months
  • You are pregnant or breastfeeding
  • You are allergic to the drugs used in this trial or similar drugs

Trial design

This is a phase 2/3 trial. The researchers need 35 to 50 people to join from hospitals in the UK.

Chemoradiation treatment
Everyone has a combination of radiotherapy and chemotherapy (chemoradiation). You have radiotherapy every day from Monday to Friday for about 6 weeks.

During radiotherapy treatment you have temozolomide tablets. You have these tablets once a day every day, including weekends. Your doctor or nurse will explain how many tablets you need to take.

You also have ABT-414 or a dummy drug (placebo). This part of the trial is randomised. The people taking part are put into treatment groups by a computer. Neither you nor your doctor will be able to decide which group you are in.  And neither of you will know which group you are in. This is called a double blind trial.

  • One group have ABT-414
  • The other group have a dummy drug (placebo) 

Diagram for INTELLANCE 1

You have ABT-414 or the dummy drug through a drip into a vein. It takes between 30 to 40 minutes. You have the drug every 2 weeks. 

You use eye drops during treatment with ABT-414 or the dummy drug. This is because ABT-414 can cause eye problems. These eye drops contain steroids Open a glossary item. They help to reduce the risk of side effects affecting your eyes. 

You start using the eye drops 2 days before each treatment with ABT-414 or the dummy drug. You use them on the day of your treatment and continue for 4 days afterwards. You put 1 to 2 drops in each eye every 8 hours for a total of 7 days. You see an eye doctor (ophthalmologist) regularly throughout the trial. They check your eyes and may change your eye drops, depending on your side effects.

After you have finished chemoradiation and ABT-414 or placebo, you have 4 weeks of no treatment.

Adjuvant therapy
You then have further treatment with temozolomide. This is standard treatment following chemoradiation for people with GBM. It is sometimes called adjuvant therapy. 

Everyone has temozolomide tablets once a day for 5 days. Then 23 days with no temozolomide. Each 4 week period is called a cycle of treatment. 

You have ABT-414 or the dummy drug in the 1st and 3rd week of each 4 week cycle. 

You continue in the same group you were in for chemoradiation. So if you had the dummy drug during chemoradiation, you continue with the dummy drug during adjuvant therapy. Neither you nor your doctor will know which group you are in. You use the eye drops in the same way you used them during chemoradiation.

You have at least 6 cycles of treatment and you might have up to 12 cycles. The number of cycles you have depends on your hospital’s policy and what your doctor recommends.

After adjuvant therapy finishes, you might continue treatment with ABT-414 or the dummy drug on its own. This would be if your brain tumour is not growing and for as long as the trial is running.

Quality of life
The trial team will ask you to fill out a questionnaire 

  • before you start chemoradiation
  • every 2 months during adjuvant therapy
  • at every follow up visit 
  • at your final visit with the trial team

The questionnaire will ask about side effects and how you’ve been feeling. This is called a quality of life study.

Blood samples
As well as routine blood tests, you have extra blood samples as part of this trial. Where possible, these samples are taken at the same time as your routine blood tests. The researchers use the extra blood samples for a variety of tests. 

For example, the researchers want to find out what happens to ABT-414 in the body (pharmacokinetics Open a glossary item). And to look for substances called biomarkers Open a glossary item to find out why treatment might work for some people and not for others.

The researchers also ask that they use one of the blood samples to look at the genetic information in your cells. If you have any further surgery the researchers would like to look at a sample of tissue removed. The genetic blood test and this extra tissue sample are optional. You can still take part in the main study if you don’t want to give these extra samples.

The researchers also ask that they use one of the blood samples to look at the genetic information in your cells. If you have any further surgery the researchers would like to look at a sample of tissue removed. The genetic blood test and this extra tissue sample are optional. You can still take part in the main study if you don’t want to give these extra samples.

Hospital visits

You’ll see the doctors and have some tests before you start treatment. The tests include 

  • eye assessment
  • blood tests
  • physical examination
  • heart trace (ECG Open a glossary item)
  • urine sample

If you join this trial before you have had your surgery, you have an MRI scan within 3 days of your operation. This is an extra scan you would need as part of this trial.
 
During radiotherapy you go to hospital every day, Monday to Friday to have your treatment. You see a doctor or nurse from the trial team every week.

During adjuvant therapy, you visit hospital to see the trial team 3 times during each cycle of treatment. A doctor will check how you are and ask about any side effects. You have an MRI scan every 2 months. 

Once you have finished adjuvant treatment and if your brain tumour is stable, you have a hospital appointment every 2 months. You have an MRI scan to measure the size of your brain tumour.

If your brain tumour starts to grow again, you finish treatment as part of this trial. Your doctor may discuss other treatment options with you. You have a final follow up visit about a month after finishing treatment. The trial team continue to collect information about your brain tumour every 3 months.  They do this by telephoning you or a friend or relative. Or by contacting your GP or by looking at your medical records.

Side effects

ABT-414 is a new drug and there might be side effects we don’t know about yet.

The main side effect of ABT-414 is eye problems. In research so far, more than half (over 50%) of people have eye problems. These include:

  • small cysts on the surface of the eye (cornea)
  • blurred vision
  • dry eyes
  • swelling of the eye tissue
  • eye pain
  • itchy eyes
  • inflammation of the cornea
  • sensitivity to light
  • watery eyes
  • feeling like something is in your eye

You use eye drops before and after each treatment to try and reduce these eye problems happening. You also see an eye doctor regularly during the trial.

Other common side effects include:

Researchers don’t yet know whether having ABT-414 with other treatments will cause more side effects or different side effects.

We have information about:

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

Dr. Paul Mulholland

Supported by

AbbVie
Experimental Cancer Medicine Centre (ECMC)

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

13731

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

Rhys was only four years old when he was diagnosed with a brain tumour

A picture of Rhys

"He went through six operations and was placed on a clinical trial so he could try new treatments.”

Last reviewed:

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