"He went through six operations and was placed on a clinical trial so he could try new treatments.”
A trial looking at olaparib with temozolomide for glioblastoma that has come back (OPARATIC)
This trial is looking at a drug called olaparib (also known as AZD2281) for a type of brain tumour called a glioblastoma. This trial is supported by Cancer Research UK.
More about this trial
Doctors usually treat glioblastoma with surgery and radiotherapy. You may also have chemotherapy. But the tumour can come back. When this happens, it may be possible for you to have more surgery, but your specialist has to take many factors into account when deciding this. The people taking part in this trial have a glioblastoma that has come back. They may or may not be having more surgery to remove it.
Doctors can also use chemotherapy if a glioblastoma comes back. Temozolomide is a chemotherapy drug they often use.
In this trial, they are looking at a drug called olaparib which is a type of biological therapy called a PARP inhibitor. PARP is an enzyme that helps damaged cells to repair themselves. If PARP is blocked, cancer cells may not be able to repair themselves after chemotherapy. This could make the chemotherapy work better. This is the first time doctors will give olaparib to people with glioblastoma and the first time they will give it with temozolomide. Doctors don’t know if olaparib will help people with glioblastoma.
The researchers have already found that olaparib can get into the brain of people with glioblastoma. The natural filter within the body that keeps harmful substances out of the brain is called the blood brain barrier. In healthy brain tissue, this barrier only allows certain drugs to cross from the blood to the brain tissues. But glioblastoma makes this barrier leaky which allows olaparib to enter the brain.
The aims of the trial are now to
- Find the best safe dose of olaparib you can have with temozolomide for glioblastoma that has come back
- Learn more about the side effects of taking these 2 drugs together
Who can enter
You can enter this trial if you
- Have been diagnosed with a glioblastoma that has come back or got worse after having other treatment
- Had radiotherapy or a combination of radiotherapy and chemotherapy to try to stop your brain tumour cancer coming back when it was first diagnosed and you managed this treatment well
- Are well enough to be up and about for at least half the day (performance status 0, 1 or 2)
- Have satisfactory blood test results
- Are willing to take a pregnancy test and to use reliable contraception during the trial and for at least 6 months afterwards if there is any chance you or your partner could become pregnant
- Are aged 18 years or older
You cannot enter this trial if you
- Have already had chemotherapy for glioblastoma that has come back
- Have had radiotherapy,
hormone therapyor immunotherapyin the last 12 weeks
- Have had biological therapy or chemotherapy in the last 4 weeks
- Have already had olaparib or another PARP inhibitor
- Have had major surgery to your chest or tummy (abdomen) that you have not fully recovered from yet
- Have had a blood transfusion in the last 4 weeks
- Have not recovered from the side effects of other treatment unless they are very mild (apart from hair loss)
- Have had fits (seizures) more than 3 times a week in the last month
- Start taking steroids (or change your dose) in the 5 days before the trial treatment starts
- Cannot have MRI scans, for example if you have a pacemaker
- Cannot swallow or absorb tablets for some reason
- Take drugs that affect an enzyme called CYP3A4 - the trial doctors can tell you which drugs these are and it is important that you don’t stop taking any medication without speaking to your doctor first
- Are not able to digest milk products (lactose intolerance)
- Have had a live vaccine in the last 4 weeks
- Have had a reaction to anything in olaparib (or anything in temozolomide or dacarbzine if you join the 2nd part of the trial)
- Have either
myelodysplasiaor acute myeloid leukaemia
- Have a heart condition that is a cause for concern
- Have an infection or any other serious medical condition that could affect you taking part in this trial
- Are taking part in any other clinical trial
- Are known to be HIV, hepatitis B or hepatitis C positive
- Are pregnant
The trial is in 3 parts. Everybody taking part will have olaparib.
The first part of the trial has been completed. It included 3 people.They had olaparib tablets twice a day for 3 days before having surgery to remove glioblastoma that had come back. They also had a dose of olaparib on the day they had surgery.
The researchers studied some of the tissue removed during surgery and found that it contained olaparib.
In the second part of the trial, the researchers looked for the highest dose of olaparib you can safely have at the same as having temozolomide. Everybody in this part of the trial had olaparib and temozolomide chemotherapy. Some people also had surgery. The first few people had a low dose of olaparib with temozolomide and the next few people had a higher dose until the researchers found the best dose. This part of the trial has now completed.
In the 3rd part of the trial the researchers are going to give the best dose of olaparib found in part 2. The researchers need around 40 people to join this part of the trial. Everybody who joins part 3 will have surgery.
You take olaparib 3 to 6 days before your surgery and on the morning of your operation. Olaparib is a tablet. You need to take the tablets as instructed by your doctor and you will be given a diary so you can note down the date and time you take them.
Once you have recovered from your surgery you start treatment with olaparib with temozolomide. Temozolomide is a capsule. Again you will be given a diary to note the date and time you take both drugs.
You take olaparib and temozolomide tablets every day for 6 weeks, followed by 2 weeks without any treatment. Each 8 week period is called a cycle of treatment. You have 3 cycles of treatment. After this, if the treatment is still helping and you don’t have any bad side effects, the trial doctors may suggest you have up to 3 more cycles.
You will see the doctors and have some tests before you start treatment. The tests include
- Physical examination
- Blood and urine tests
- Heart trace (
- Chest X-ray
- MRI scan of your brain
In part 3 of the trial you have 3 extra MRI scans of your brain. These are to help the doctors learn more about how a brain tumour affects the structure of the brain and how olaparib works on the tumour. You have 2 scans in the week before you start taking olaparib and 1 the day before your surgery.
You go to hospital the first day you take olaparib. You can take the tablets at home for the next couple of days. When you have surgery, you go back into hospital on the 3rd day, stay overnight and have your surgery the next day. You have another dose of olaparib in the morning, before your surgery.
After the operation you will probably need to stay in hospital for between 2 and 7 days, but this will depend on how you recover. You go back to see the trial team within a few weeks of having surgery.
You have a physical examination and blood tests before starting treatment with temozolomide and olaparib. You go to hospital every week during the 1st cycle of treatment, and then every 2 weeks during the rest of your treatment. You have an MRI scan 8 weeks during treatment.
When you finish treatment, you will see the trial team again 4 weeks later. At this visit you have an ECG, blood and urine tests. You may need to have an MRI scan if you have not had one recently. You finish taking part in the study at this point. But if you have side effects from the trial treatment, you will see the trial team until the side effects get better.
As olaparib is a new drug and this is the first time it is being used to treat glioblastoma, there may be some side effects we don’t know about yet. The side effects that we know about include
- A drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
- Feeling or being sick
- Tiredness (fatigue)
- Inflammation of the lungs which can cause breathlessness
Your doctor will explain more about having surgery and what to expect. You will be able to ask them any questions you have.
We have more information about the possible side effects of temozolomide.
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.
Professor Anthony Chalmers
Cancer Research UK (Centre for Drug Development)
Experimental Cancer Medicine Centre (ECMC)
NIHR Clinical Research Network: Cancer
This is Cancer Research UK trial number CRUKD/11/006.