A study looking at rucaparib for ovarian cancer that has come back (ARIEL2)

Cancer type:

Ovarian cancer

Secondary cancers

Status:

Results

Phase:

Phase 2

This study looked at rucaparib for ovarian cancer that had gone away or got smaller after platinum chemotherapy.

It had 2 parts. Part 1 was for people whose cancer had come back 6 months after their last platinum dose Open a glossary item

. Part 2 was for people whose cancer had come back and who had 3 to 4 different courses of chemotherapy.

The study was for people who had:

Also, they had a serous type cancer that was high grade. High grade means that the cancer is more likely to grow quickly.

These cancers are all treated in the same way. So, when we use the term ovarian cancer in this summary, we are referring to all 3.

There were 2 parts to this study. This summary includes results for part 1. We hope to add results for part 2 when they become available.

More about this trial

Ovarian cancer often responds well to chemotherapy that includes a platinum drug Open a glossary item

such as carboplatin. But after a while it may start growing again. So, researchers are looking for ways to improve treatment. In this study, they looked at a drug called rucaparib.

Rucaparib is a type of drug known as a PARP inhibitor. PARP is an enzyme Open a glossary item

that helps damaged cells to repair themselves. Cancer cells may not be able to repair themselves if PARP is blocked.

Researchers took tissue and blood samples. They looked for substances such as DNA Open a glossary item

or proteins. These can show how the cancer is responding to treatment. They are called biomarkers Open a glossary item

Doctors know about some cancer biomarkers. For example, a change, or mutation in one of the breast cancer susceptibility genes (also known as BRCA genes) is a biomarker for some types of cancer. This includes breast and ovarian cancer. But in people with a normal BRCA gene it’s difficult to know who will respond best to rucaparib. So, researchers ran a study to find out more.

The aims of this study were to:

predict who rucaparib worked best for
find out how well treatment worked
find out more about the side effects

Summary of results

The study team found that rucaparib worked best for people with a BRCA gene change in the ovarian cancer cells. And for people with normal BRCA gene who had a higher level of DNA change in the ovarian cancer cells.

This study was open for people to join between 2013 and 2014. Researchers published the results in 2017.

About this study

204 patients were treated with rucaparib in this phase 2 study. 28 were still having treatment when the researchers analysed the results.

Samples

Researchers tested samples of tumour and blood to find out if they had genes changes (mutations). They looked at:

the BRCA gene change
levels of DNA change in the cancer cells

The researchers had the results for 192 people, and:

40 people had a BRCA gene change
152 people had a normal BRCA gene

The researchers then looked at the 152 samples to find out if they had a specific type of DNA change.

They found:

82 had higher levels of DNA change (genomic scarring) (this is called LOH high)
70 had a lower levels of DNA change (this is called LOH low)

Results

People had treatment for an average of just under 6 months. The researchers looked at how long before the cancer got worse in each of these groups.

This was:

just under 13 months in people with a BRCA gene change
5.7 months in people who had higher levels of DNA change (LOH high)
5.2 months in people who had lower levels of DNA change (LOH low)

At 12 months they looked at whose cancer hadn’t started to grow again. This was:

5 out of 10 women (50%) with a BRCA gene change
just under 3 out of 10 women (28%) with higher levels of DNA change (LOH high)
1 out of 10 women (10%) who had lower levels of DNA change (LOH low)

So, the study team say that rucaparib worked best for people who had the BRCA gene change. And a bit better for people who had a higher level of DNA changes compared with those who had a lesser degree of change.

Treatment worked best in people who had 1 to 2 previous treatments with platinum chemotherapy compared with those who had 3 or 4. And if the chemotherapy had worked well.

Side effects

Rucaparib did cause some side effects, but they were mostly mild or moderate. The most common side effects were:

feeling or being sick
tiredness (fatigue)

Conclusion

The study team concluded that rucaparib worked best for people who had a BRCA gene change. Or for people with a normal BRCA gene who had higher levels of DNA changes.

The researchers suggest that testing tumour samples for DNA changes is useful. It can help identify if people with a normal BRCA gene change might respond to treatment or not.

The second part of ARIEL2 is looking at rucaparib in a larger group of people. These results aren’t available yet, but we hope to add them when they are.

Where do these results come from

We have based this summary on information from the research team. The information they sent us has been reviewed by independent specialists (peer reviewed Open a glossary item

) and published in a medical journal. The figures we quote above were provided by the trial team who did the research. We have not analysed the data ourselves.