A trial looking at a PARP-1 inhibitor for advanced cancer, particularly in people with a BRCA gene mutation

This trial was looking at a new treatment called AZD2281 for advanced solid tumours. More than a third of the people who took part in this trial had a BRCA gene fault.

PARP-1 is an enzyme that helps damaged cells to repair themselves. PARP stands for “poly ADP-ribose polymerase” and is found in some cancer cells.

Doctors hope that if they can stop PARP-1 working, the cancer cells will not be able to repair themselves and will die. This type of treatment is called a ‘PARP-1 inhibitor’. The PARP-1 inhibitor in this trial is called AZD2281. It was formerly known as KU-0059436 and is also called olaparib.

The main aims of this trial were to find out

The best dose of AZD2281 to give
What happens to AZD2281 in the body
What the side effects are
How well AZD2281 worked

Recruitment

Start 01/07/2005

End 31/03/2008

Phase

Phase 1

Summary of results

The trial team found that AZD2281 can have an effect on cancer in people with a BRCA gene fault, without causing too many side effects.

The trial recruited 60 people. 22 of them were known to have a BRCA gene fault.
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The first few people had a low dose of AZD 2281. As they didn’t have too many bad side effects, the next few people had a higher dose and so on until the researchers worked out the best dose to give. This is called a dose escalation study.

The side effects that people did have included

Mood changes
Fatigue
A drop in the number of platelets, which can cause bleeding problems
Feeling sleepy (somnolence)
Effects on the digestive system

Side effects were no worse in the group of people with the BRCA gene fault.

The researchers learnt more abut how the drug worked in the body and found that it had an effect on cancer in people with the BRCA gene fault. The cancer got smaller in nearly half the people with the gene fault. But cancers did not respond to AZD2281 in the other people taking part in this trial.

The researchers found a safe dose of AZD2281 to give that did not cause too many side effects. And they found that this drug had some effect on cancers in people with a BRCA gene fault.

We have based this summary on information from the team who ran the trial. The information they sent us has been reviewed by independent specialists (peer reviewed) and published in a medical journal. The figures we quote above were provided by the trial team. We have not analysed the data ourselves.