A trial looking at olaparib with temozolomide for glioblastoma that has come back (OPERATIC)

This trial is looking at a drug called olaparib (also known as AZD2281) for a type of brain tumour called a glioblastoma.

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 and their doctors think they may benefit from 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. This is because there is a natural filter within the body that keeps harmful substances out of the brain. It is called the blood brain barrier and in healthy brain tissue, it only allows certain drugs to cross from the blood to the brain tissues. But a glioblastoma can make this barrier leaky and researchers hope this will allow the olaparib to enter the brain.

The first aim of this trial is to see if olaparib can cross the blood brain barrier and reach the glioblastoma in a small group of patients. If the researchers find that it can, they then want 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

Recruitment

Start 18/07/2011

End 07/10/2014

Phase

Phase 1

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 and your specialist thinks you can have surgery to remove it
Had radiotherapy or a combination of radiotherapy and chemotherapy to try to stop your brain tumour cancer coming back when it was first diagnosed
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 between 18 and 70 years old
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

You cannot enter this trial if you

Have already had chemotherapy for glioblastoma that has come back
Have had radiotherapy, hormone therapy or immunotherapy in the last 12 weeks, 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 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 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

Trial design

The trial is in 2 parts. Everybody taking part will have olaparib and surgery.

The first part of the trial will include 6 people. They will have olaparib tablets twice a day for 3 days before having surgery to remove glioblastoma that has come back. They also have a dose of olaparib on the day they have surgery.

The researchers will study some of the tissue removed during surgery to see if it contains olaparib. If they can see it does in at least 1 person, the trial will go into the next stage.

In the second part of the trial, the researchers are looking for the highest dose of olaparib you can safely have at the same as having temozolomide. It will recruit up to 28 people who have glioblastoma that has come back. They will have olaparib, surgery and temozolomide chemotherapy.

The first few people will have a low dose of olaparib. If they don’t have any serious side effects, the next few people will have a higher dose. And so on, until the researchers find the best dose to give. This is called a dose escalation study.

People joining this part of the trial have olaparib before surgery in the same way as people in part 1. But some people may only take it once a day at this point. They also start having olaparib again alongside temozolomide once they have recovered from their surgery.

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.

Hospital visits

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

Physical examination
Blood and urine tests
Heart trace (ECG)
Chest X-ray
MRI scan of your brain

You have 2 more MRI scans in the week before you start olaparib, and another one the day before you have surgery.

You go to hospital the first day you take olaparib. You can take the tablets at home for the next couple of days. The trial team will ask you to fill in a diary to show when you take the tablets.

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.

People in part 1 go back to see the trial team 4 weeks after having surgery. You have a physical examination, an ECG, blood and urine tests. At this point, you finish taking part in the study. But if you have any side effects from the study drug you will see the trial team until the side effects get better. Otherwise, you will carry on your treatment under the care of your specialist.

People in part 2 go back to see the trial team within 3 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 2 days after surgery and then every 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.

Side effects

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.

There is more information about the possible side effects of temozolomide on CancerHelp UK.