A trial of olaparib with radiotherapy and chemotherapy for glioblastoma (PARADIGM-2)

Cancer type:

Brain (and spinal cord) tumours

Status:

Open

Phase:

Phase 1

This trial is looking at whether a drug called olaparib improves the way radiotherapy and chemotherapy work. It is for people with a type of brain tumour called glioblastoma who:

  • are newly diagnosed
  • have recently had surgery

Cancer Research UK supports this trial.

More about this trial

Glioblastoma is one of the most common types of brain tumours in adults. Surgery and radiotherapy are the usual treatments. You might also have a chemotherapy drug called temozolomide. 

Olaparib is a type of biological therapy Open a glossary item called a PARP inhibitor. PARP is a protein that helps cells to repair. If PARP is blocked, cancer cells might not be able to repair themselves after chemotherapy or radiotherapy. In this trial, doctors hope that having olaparib might make these treatments work better. But they aren’t sure, so want to find out more. 

Glioblastoma tumour cells have areas of DNA Open a glossary item called MGMT. These areas can be low (methylated) or high (unmethylated). We know from recent research that people whose tumours have:

  • low MGMT seem to benefit from temozolomide
  • high MGMT do not benefit from temozolomide

As part of this trial, you won’t have temozolomide if you have unmethylated MGMT. But it might be possible to have higher and more frequent doses of olaparib with radiotherapy. The researchers will do a MGMT test before you start treatment. 

So far, a small number of people with glioblastoma have had olaparib and radiotherapy. And a small number have had olaparib and chemotherapy. But this is the first time people will have all 3 together.

The aims of the trial are to:

  • find the highest safe dose of olaparib with chemotherapy and radiotherapy
  • find out if having olaparib helps chemotherapy and radiotherapy work better
  • learn more about the side effects

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

  • You have a fast growing (grade 4) glioblastoma
  • The trial team tested a sample of your cancer taken during surgery or a biopsy Open a glossary item when you were diagnosed to find out your MGMT status
  • You can start radiotherapy within 6 weeks of having surgery
  • You are well enough to carry out all your normal activities apart from heavy physical work (performance status 0 or 1)
  • You have satisfactory blood test results
  • You are willing to use 2 forms of reliable contraception during the trial and for up to 6 months afterwards if there is any chance that you or your partner could become pregnant
  • You are under 70 years old

You cannot join this trial if any of these apply. You

  • Have already had radiotherapy or other treatment for your brain tumour or cancer spread to the spinal cord (central nervous system)
  • Have already had olaparib or treatment with another PARP inhibitor
  • Are not able to swallow tablets or capsules
  • Have myelodysplastic syndrome or acute myeloid leukaemia
  • Have had a blood transfusion with red blood cells in the 28 days before joining the trial
  • Have had major surgery in the last 2 weeks and you have not fully recovered
  • Are known to be sensitive to olaparib, temozolomide or dacarbazine or anything they contain
  • Have taken any medication that blocks CYP enzymes in the 3 weeks before joining the trial
  • Have had treatment with an experimental drug in the last month
  • Have fits (seizures) that are not controlled with medication
  • Have had any other cancer in the past 5 years apart from non melanoma skin cancer Open a glossary item or carcinoma insitu of the cervix (CIS)
  • Have HIV
  • Have hepatitis B or hepatitis C
  • Are pregnant or breastfeeding

Trial design

This phase 1 trial is based in the UK. The researchers need 68 people to take part.

You are put into 1 of 2 treatment groups depending on whether your tumour has methylated or unmethylated MGMT. The trial laboratory team will test a tissue sample taken when you had surgery or a biopsy to check for this. The MGMT testing will take less than 10 days but this won’t delay the start of your treatment. 

If you have:

  • low (methylated) MGMT you have olaparib, radiotherapy and the chemotherapy drug temozolomide
  • high (unmethylated) MGMT you have olaparib and radiotherapy

PARADIGM-2 trial diagram

If it isn’t possible to find out your MGMT status, you won’t be able to join the trial. Your doctor will discuss other treatment options with you.

Treatment for low (methylated) MGMT

You have:

  • the usual dose of radiotherapy every day (Monday to Friday) for 6 weeks
  • olaparib tablets starting on the 1st day of radiotherapy and for 4 weeks after it finishes
  • temozolomide capsules once every day starting on the 1st day of radiotherapy and stopping when it finishes

How often you have olaparib each week depends on when join the trial. The trial team can tell you more about this. You have a short break from temozolomide then restart it about a month after radiotherapy ends. This time you have it for 6 months.

Treatment for high (unmethylated) MGMT

You have:

  • the usual dose of radiotherapy everyday (Monday to Friday) for 6 weeks
  • olaparib tablets once every day starting 3 days before radiotherapy and for 4 weeks after it finishes

Both groups

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

The dose of olaparib and how often you have it depends on the dose level being tested when you join. You have the same dose during the trial as long as the side effects aren’t too bad. If you do have bad side effects, your doctor might decide to reduce it or stop it.

Research samples

The researchers will ask for a sample of tissue (biopsy Open a glossary item) that was removed when you had surgery or a biopsy. They will also ask for 3 extra blood samples. These samples will be used in future studies to find out more about glioblastoma. 

If you don’t want to give these samples, you don’t have to. You can still take part in the trial.

Hospital visits

You see a doctor and have some tests before you can take part. These include:

  • a physical examination
  • blood tests
  • MRI scan
  • MGMT testing of your tumour

You see the trial doctor for a check up:

  • once a week during radiotherapy
  • 2 and 4 weeks after radiotherapy finishes

After finishing radiotherapy you have an MRI:

  • after 4 weeks
  • then every 3 months

The trial team will follow you up at clinic appointments every 3 months.

Side effects

As having olaparib with radiotherapy and chemotherapy is a new treatment, there might be side effects we don’t know about yet. The trial team will monitor you during the time you have treatment and you’ll have a phone number to call them if you are worried about anything. 

So far, the most common side effects of olaparib include:

We have information on the side effects of:

Olaparib might increase the side effects caused by radiotherapy or chemotherapy or make the side effects worse. Your doctor will talk to you about the side effects of treatment before you agree to take part.

Location

Bristol
Cambridge
Cardiff
Glasgow
Leeds
Manchester

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

Professor Anthony Chalmers

Supported by

Cancer Research UK

AstraZeneca

NHS Greater Glasgow and Clyde

The Brain Tumour Charity

University of Glasgow

Other information

This is Cancer Research UK trial number CRUKD/16/010.

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

14194

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:

Rate this page:

No votes yet
Thank you!
We've recently made some changes to the site, tell us what you think