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

Cancer type:

Brain (and spinal cord) tumours

Status:

Results

Phase:

Phase 1

This trial looked at olaparib for a type of brain tumour called a glioblastoma that had started to grow again after treatment. It was supported by Cancer Research UK.

More about this trial

Glioblastoma is a type of brain tumour. Doctors sometimes use a chemotherapy drug called temozolomide (Temodal) to treat glioblastoma that has come back after surgery and radiotherapy.

In this trial, they looked at a drug called olaparib (AZD2281 or Lynparza) in combination with temozolomide. Olaparib is a type of targeted cancer drug 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.

The research team had already done part 1 of this trial, which showed that olaparib could cross the blood brain barrier. This is a natural filter between the blood and the brain, which protects the brain from harmful substances. Only some drugs can cross the blood brain barrier.

The results below are for part 2 of the trial. The aims of this part were to:

find the best dose of olaparib to have with temozolomide for glioblastoma that has come back
learn more about the side effects of taking these 2 drugs together

Summary of results

Part 2 of this trial recruited 45 people who had already had treatment for their glioblastoma, but it had started to grow again. Everyone taking part had both olaparib and temozolomide.

This trial was a dose escalation study. This means that the first few people who took part had the lowest dose of olaparib. The next few people had a higher dose. The research team had planned to increase the dose further, but found that it caused too many side effects.

They also found that having olaparib every day caused too many side effects. This meant they had to either delay or reduce the next dose people had. So they changed the schedule to have it for 5 days out of every 7. And then changed it again to have it for 3 days out of every 7.

About 8 out of 10 people (80%) who took part had at least 1 side effect. Some were mild or didn’t last long, but some were more serious.

The most common side effects were:

feeling sick
a drop in cells that help the blood to clot (platelets)
a drop in a type of white blood cell called lymphocytes
extreme tiredness (fatigue)

The research team were able to look at how well the treatment worked in 32 of the people who took part. They found that the glioblastoma had:

got smaller in 1 person
stayed the same in 17 people
continued to grow in 14 people

For 14 of the people who took part, it was 6 months or longer before their brain tumour started to grow again. This is similar to results of other trials for people in this situation.

The research team concluded that olaparib could be a useful treatment for glioblastoma because it can cross the blood brain barrier. And that intermittent olaparib with temozolomide didn’t cause too many side effects in this group of patients. The combination of olaparib and temozolomide is now being looked at alongside radiotherapy, in a trial called Paradigm 2.

We have based this summary on information from the research team. As far as we are aware, the information they sent us has not been reviewed independently (peer reviewed Open a glossary item ) or published in a medical journal yet. The figures we quote above were provided by the research team. We have not analysed the data ourselves.