A trial looking at olaparib and radiotherapy for people with glioblastoma (PARADIGM)

Cancer type:

Brain (and spinal cord) tumours

Status:

Open

Phase:

Phase 1/2

This trial is looking at olaparib and radiotherapy for people with a type of brain tumour called a glioblastoma who cannot have standard treatment. This includes people over the age of 70 and younger people who have poor health.

Cancer Research UK supports this trial.

More about this trial

Glioblastoma is the most common type of primary brain tumour. Doctors can treat glioblastomas with chemotherapy and radiotherapy.  But people over the age of 70 and those who have poor health often have radiotherapy alone. This is because these people have less benefit and more side effects from having both chemotherapy and radiotherapy.

Early research has shown that a type of biological therapy called olaparib can make radiotherapy work better. In this trial, doctors want to see if olaparib with radiotherapy improves the outlook (prognosis Open a glossary item) for people who are not suitable for combination chemotherapy and radiotherapy treatment.

The trial is in 2 parts. The aim of the first part was to find the best dose of olaparib to have with radiotherapy.

The aims of the second part are to see if the treatment helps people to live longer and also to learn more about the side effects and how the treatment might affect people’s daily life. 

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 you have been diagnosed with a glioblastoma and are in one of the following situations

  • You are between 18 and 69 years of age and are well enough to be up and about for at least half the day (performance status 2 )
  • You are over 70 and are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
  • Your doctor doesn’t think having both chemotherapy and radiotherapy is a suitable treatment for you

And all of the following apply. You

  • Have satisfactory blood test results
  • Have satisfactory urine test results
  • Are able to swallow tablets or capsules
  • Are willing to use reliable contraception during treatment and for 3 months afterwards if there is a chance you or your partner could become pregnant

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

  • Have had radiotherapy or chemotherapy for a central nervous system (CNS) Open a glossary item cancer
  • Have had surgery in the last 2 weeks
  • Have had an experimental drug in the last 4 weeks
  • Have had a type of biological therapy called a PARP inhibitor including olaparib (your doctors can advise you about this)
  • Have had a blood transfusion in the last 4 weeks
  • Have myelodysplastic syndrome or acute myeloid leukaemia
  • Have had any other cancer in the last 5 years apart from carcinoma in situ of the cervix or non melanoma skin cancer that was successfully treated
  • Have fits (seizures) that are not controlled with medication
  • Have hepatitis B, hepatitis C or are HIV positive
  • Are known to be allergic to olaparib
  • Take certain drugs that could affect how well olaparib works, these include some antibiotics or drugs to treat fungal infections, some drugs used to treat fits and the herbal medicine St John’s wort (your doctor can advise you about this)
  • Are pregnant or breastfeeding

Trial design

This trial is in 2 parts and is called a phase 1/ 2 trial.  For the first part of the trial (phase 1) doctors need between12 and 24 people to take part. For phase 2, they need around 140 people.

In phase 1, the doctors wanted to find the best dose of olaparib to give with radiotherapy. The first 3 to 6 people who joined the trial had a low dose of olaparib. If they did’t have bad side effects the next 3 to 6 people had a higher dose. The doctors aimed to look at 4 different doses of olaparib. 

Everyone in phase 1 took olaparib:

  • 3 days before starting radiotherapy
  •  During radiotherapy
  • 4 weeks after the radiotherapy has finished. 

Everyone had radiotherapy for 3 weeks once a day Monday to Friday. 

Please note: Phase 1 of the trial is now closed and phase 2 is now open to recruitment. 

In phase 2, the doctors will compare 2 groups. One group will have the best dose of olaparib (decided in phase 1) and radiotherapy. The other group will have a dummy drug and radiotherapy.

Phase 2 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. Open a glossary item

Everyone in phase 2 will take either olaparib or a dummy drug

  • 3 days before starting radiotherapy
  • During radiotherapy
  • 4 weeks after the radiotherapy has finished.

Everyone has radiotherapy for 3 weeks once a day Monday to Friday. Olaparib and the dummy drug are tablets you take twice a day. 

 

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

You will also do a memory test called a mini mental status exam.  You do this before you start treatment, when you finish treatment, and then during your follow up appointments.

Hospital visits

You see the trial team and have some tests before you start treatment. These include

You will need to go to hospital for your radiotherapy treatment. This will be once a day from Monday to Friday.  During your treatment you will see the trial team and have regular blood tests. 

You see the trial team and have blood tests

  • 2 weeks after you finish radiotherapy
  • When you finish taking the tablets
  • 4 weeks after finishing the tablets
  • 8 weeks after finishing the tablets

In part 2 of the trial some of the blood tests you have during your radiotherapy and 2 weeks after you finish will be for research. The doctors want to see how the tablets are working in your body. You might hear these tests called pharmacokinetics Open a glossary item. The trial team will explain more about this. 

When you go to hospital 8 weeks after finishing the tablets you will have another MRI scan of your brain.

The trial team will then see you every 2 months for up to 2 years.

Side effects

The following are common side effects of olaparib

The most common side effects of radiotherapy to the brain are

  • Hair loss
  • Feeling and being sick
  • Headache
  • Feeling drowsy
  • Blurred vision
  • A red scalp
  • Muscle weakness
  • Fits
  • An increase in the symptoms you had when your brain tumour was diagnosed

We have more information about brain radiotherapy side effects.

Location

Brighton
Bristol
Cambridge
Coventry
Edinburgh
Glasgow
London
Manchester
Sheffield

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

AstraZeneca
Cancer Clinical Trials Unit Scotland
Cancer Research UK
Experimental Cancer Medicine Centre (ECMC)
NHS Greater Glasgow & Clyde
NIHR Clinical Research Network: Cancer
University of Glasgow

Other information

This is Cancer Research UK trial number CRUK/13/034.

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

11764

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