A trial looking at a new drug called rucaparib for breast and ovarian cancer, in people with BRCA gene faults (PH2/052)

This trial is to find out how well a new treatment called rucaparib (also known as CO-338, AG-014699, or PF-01367338) works. The trial is for people with an inherited fault in the BRCA1 or BRCA2 gene who have locally advanced or advanced breast cancer, or advanced ovarian cancer. Women who have serous ovarian cancer that is high grade can take part in the trial even if they do not have a BRCA gene fault.

Rucaparib is a type of treatment called a PARP-1 inhibitor. This means it blocks an enzyme called PARP-1, which helps damaged cells to repair themselves. PARP stands for poly ADP-ribose polymerase and is found in all cells, including cancer cells.

The cells in your cancer already have problems with repairing cell damage, because of the BRCA gene fault. Doctors hope that if they can stop PARP-1 working, the cancer cells containing BRCA gene faults will not be able to repair themselves and will die. Although PARP-1 will be blocked in all the other cells in your body, these healthy cells are able to repair themselves because they do not have the BRCA gene fault.

Early research in the laboratory has shown that rucaparib can stop cancer cells that have BRCA gene faults from repairing themselves. The aim of this trial is to find out

How well rucaparib works as a treatment for breast and ovarian cancer in people with BRCA gene faults and for high grade serous ovarian cancer without the BRCA gene fault
What the side effects are
What happens to rucaparib inside the body

Recruitment

Start 12/12/2007

End 30/08/2013

Phase

Phase 2

Who can enter

You can enter this trial if you are a man or woman and

Have stage 3 or stage 4 breast cancer, stage 3 or stage 4 ovarian cancer, or high grade serous ovarian cancer
Have a faulty BRCA1 or BRCA2 gene, or your doctors think it is very likely that you have one of these faulty genes - you have a test for this before you can start treatment, but if you have high grade serous ovarian cancer, you can join the trial if you don't have a BRCA gene fault
Have had no more than 5 chemotherapy regimes in the last 5 years, and if you have ovarian cancer, your last treatment with cisplatin or carboplatin was at least 2 months ago (if you have high grade serous ovarian cancer, your last treatment with cisplatin or carboplatin needs to be at least 6 months ago)
Have cancer which can be measured on an X-ray or scan (this does not include cancer that has spread to your bones, or areas of cancer that have been treated with radiotherapy)
Are well enough for treatment (performance status 0 or 1)
Have satisfactory heart and blood test results
Are prepared to use reliable contraception, while you are taking part in the trial, if there is any chance you or your partner, could become pregnant
Are at least 18 years old

You cannot enter this trial if you

Have cancer that has spread to your brain (secondary brain cancer)
Have had hormone therapy, immunotherapy or chemotherapy in the last 4 weeks (or 6 weeks if you had mitomycin, lomustine, carmustine or streptozocin)
Had radiotherapy within the last 4 weeks, unless this was to help with symptoms (palliative radiotherapy)
Are still having side effects from previous treatment
Have had major surgery to your chest or abdomen in the last 4 weeks, and you still have side effects from this surgery
Have had any other serious medical condition or infection that the doctors think will affect the treatment in this trial, including heart disease
Have had a PARP inhibitor before
Have any other cancer apart from non melanoma skin cancer, carcinoma in situ of the cervix or breast cancer and ovarian cancer (if you previously had treatment to cure another type of cancer, but a biopsy shows that cancer has come back somewhere else in the body, you can take part)
Are pregnant or breastfeeding

Trial design

This is a phase 2 trial and will recruit about 84 people. Everyone taking part will take the trial drug rucaparib. To begin with, researchers were looking at giving rucaparib through a drip into a vein. But people joining the trial now take tablets.

Each 3 week period is one cycle of treatment. You take rucaparib tablets once a day on either 7, 14 or 21 days of each treatment cycle.

The first people having the new tablet form of rucaparib will take it for the first 7 days of each treatment cycle. If they do not have any serious side effects, the next people will take it for 14 days of each cycle. If they do not have any serious side effects, the next people will take it for 21 days (every day) of each cycle. It there are still no serious side effects, the doctors will increase the dose and the rest of the people joining the trial will have a higher dose of rucaparib for 21 days of each treatment cycle. This is called a dose accumulation or escalation study.

If tests show that the treatment is working well, and you are not having too many side effects, you may be able to continue with this treatment for up to 12 cycles of treatment. The exact number will depend on how well the treatment works. Some people may be able to have more than 12 cycles of treatment.

The researchers would like to look at a sample of your cancer. If you agree, they would like to take a sample (biopsy) of your cancer. And they would like to look at the biopsy sample that was kept by the hospital when you had your first biopsy or surgery.

Hospital visits

Before you can join this trial, you will need some tests. These include

Blood tests
Heart trace (ECG)
CT scan
Chest X ray (if you have not had a chest CT scan before)
A test of how well your heart is beating - either a heart ultrasound (echocardiogram) or a MUGA scan

The doctors would like to take an extra blood sample before you start treatment. They will use this to look at the genes that control how rucaparib is removed by the body, and the genes which control levels of the PARP-1 enzyme. This is called genotyping.

You can have treatment as an outpatient. So some days you will go to the hospital for treatment, the rest of the time you take the tablets at home. The trial team will give you full instructions about how to take rucaparib. They will also give you a diary card to record when you take your medication.

You will have extra blood tests during the first and second cycles of treatment. Depending on the group you are in, you then have blood tests on up to 4 different days in each cycle. You have an ECG on 3 different days in each cycle. You have a CT scan or MRI scan every 6 weeks.

If you have more than 12 cycles of treatment, you will then only have blood tests on the first day of each treatment cycle. And you have a scan every 12 weeks.

You will see the doctors about 4 weeks after you finish treatment. You have blood tests, an ECG, a chest X-ray and you may have another CT scan. The doctors will follow your progress for a year, or until you start having other treatment.

If you stop the trial treatment for any reason other than your cancer getting worse, the trial team will monitor your progress every 3 months until your cancer does get worse.

Side effects

Rucaparib is a new treatment, and we don’t know much about the side effects yet. Possible side effects that doctors know about so far include a drop in blood cell counts. This can cause tiredness, shortness of breath, an increased risk of infection or bleeding problems.