A trial looking at olaparib and radiotherapy for people with glioblastoma (PARADIGM)
Please note - this trial is no longer recruiting patients. We hope to add results when they are available.
Cancer type:
Status:
Phase:
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 65 and younger people who have poor health.
Please note, the sub study is open to recruitment. The main study is closed. You can find out about the sub study in the trial design section below.
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. People over the age of 65 often have radiotherapy only and also have a shorter course of treatment. People 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) 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 65 years of age and are well enough to be up and about for at least half the day (performance status 2 )
- You are over 65 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) 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
Sub study - open to recruitment
The team are doing a small sub study. You might be suitable to join the sub study if tests on done a sample of glioblastoma show you have methylated MGMT. This means that you might benefit from having chemotherapy.
Researchers want to find out how safe it is to have olaparib with radiotherapy and a chemotherapy drug called temozolomide. They also want to find the best dose of olaparib when given in combination with radiotherapy and temozolomide.
In the sub study you have olaparib, radiotherapy and temozolomide.
Your doctor will check if you are suitable for the sub study. They will then tell you more about it and how often you have treatment.
Main study - closed to recruitment
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 between 12 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 didn’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.
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.
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
- MRI scan of your brain
- Physical examination
- Blood tests
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. 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
- An increased risk of getting an infection from a drop in white blood cells
- Tiredness and breathlessness due to a drop in red blood cells (anaemia)
- Bruising more easily due to a drop in platelets
- Tiredness and weakness (fatigue)
- Feeling and being sick
- Loss of appetite
- Diarrhoea
- Indigestion
- Sore mouth
- Pain in the upper part of your abdomen
- Taste changes
- Headache
- Dizziness
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.
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.
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.
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
