A study of rucaparib for prostate cancer that has spread elsewhere in the body (TRITON2)

Please note - this trial is no longer recruiting patients. We hope to add results when they are available.

Cancer type:

Prostate cancer

Status:

Closed

Phase:

Phase 2

This study is for men whose prostate cancer has got worse despite hormone therapy.

More about this trial

The usual treatment for prostate cancer that has spread is chemotherapy and hormone therapy. But sometimes this stops working, so doctors want to improve treatment.

In this study, they are looking at a drug called rucaparib (or CO-338). It has been looked at in women with ovarian cancer but not yet in patients with prostate cancer. It is a type of targeted cancer drug known as a PARP inhibitor. PARP is a protein that helps damaged cells repair themselves. If PARP is blocked, then cancer cells might not be able to repair themselves.

Cancer cells with certain gene changes (mutations Open a glossary item ) already have problems repairing themselves. We know from research that PARP inhibitors might help men whose prostate cancer cells have mutations including:

BRCA 1
BRCA 2
ATM
other genes linked with DNA repair

The researchers hope that by blocking PARP, cancer cells with these mutations won’t be able to repair themselves and will die.

The aims of the study are to:

find out how well treatment works
look for substances called biomarkers to find out which men with prostate cancer might benefit most from rucaparib
learn more about the side effects
find out more about quality of life

Who can enter

The following bullet points list the entry conditions for this study. Talk to your doctor or the study team if you are unsure about any of these. They will be able to advise you.

You might be able to join this study if all of the following apply.

You have adenocarcinoma of the prostate gland or cancer cells that look very abnormal under a microscope (poorly differentiated)
Your cancer has spread to other parts of your body (metastatic prostate cancer) and is getting worse
Your prostate cancer got worse after treatment with both of the following:
- at least 1 but no more than 2 hormonal treatments such as abiraterone, apalutamide
  or enzalutamide
- 1 course of chemotherapy that included a taxane drug such as docetaxel
You have had surgery to remove your testicles or have been taking drugs to lower the level of testosterone in your body (luteinising hormone agonists such as goserelin or leuprorelin)
After you started your most recent anti-cancer treatment, your disease got worse in one of the following ways:
- 2 blood tests at least 1 week apart showed the level of PSA in your blood was rising
- On a scan there were new areas of cancer or the existing areas got worse
- A bone scan showed at least 2 new areas of cancer spread in the bone
Your cancer cells have a mutation in the BRCA1, BRCA2 or ATM gene, or other genes linked with DNA repair
You are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
You are willing to use reliable barrier contraception during treatment and for 6 months afterwards if you are sexually active
You have satisfactory blood test results
You are at least 18 years old

You cannot join this study if any of these apply. You

Cancer related

Have a type of prostate cancer called small cell or high grade neuroendocrine
Have cancer that has spread to your brain or spinal cord and is causing symptoms
Have cancer that is pressing on your spinal cord (spinal cord compression )
Have already had a drug that blocks PARP, platinum drugs , or the chemotherapy drugs cyclophosphamide or mitoxantrone
Have had any anti cancer treatment in the 2 weeks before starting treatment in this study apart from radiotherapy
Take denosumumab or drugs called bisphosphonates unless you have been having the same dose for at least 30 days before starting study treatment
Have any other cancer that the doctors think may affect your participation in the trial
Have not recovered from the side effects of other cancer treatment unless they are mild, apart from hair loss

Medical conditions

Have a stent in your duodenum or any other digestive system problem that would affect how you absorb the study drug
Have had a minor operation in the last 5 days or a larger operation in the 21 days before starting rucaparib
Have HIV or AIDS
Have hepatitis B or hepatitis C
Have any other serious medical condition or mental health problem that the study team think could affect you taking part

Trial design

This phase 2 study is taking place worldwide. The researchers need 360 men to take part including about 20 from the UK.

Everybody who agrees to take part has a tissue sample (biopsy) or a blood sample tested for the specific gene changes, unless this has been done already. The researchers might test a tissue sample taken when you previously had surgery or a biopsy, or they might ask to take a new biopsy sample or blood sample.

If you have the gene changes they are looking at, you might be suitable to take part in the study. If not, your doctor will discuss other treatment options with you.

Treatment
Rucaparib is a tablet. You take the tablets twice a day, everyday. You have treatment for as long as it is working and the side effects aren’t too bad.

In some cases, you might continue treatment if your cancer gets worse and your doctor thinks this is in your best interest. But the study team can tell you more if this applies.

Samples for research
You have some extra blood tests as part of this study. Where possible, you have these at the same time as your routine blood tests. They plan to use these samples to look at:

what happens to rucaparib in the body (pharmacokinetics )
biomarkers to help work out why treatment might work for some men and not for others

The doctors might ask to take some extra tissue samples (biopsies) when you finish treatment. You don’t have to agree to this if you don’t want to. You can still take part in the study.

The study team hope to use any leftover samples for future research.

Quality of life
The study team ask you to fill out some questionnaires. You do this before you start treatment and at set times during treatment.

The questionnaire asks about side effects and how you’ve been feeling. This is called a quality of life study.

Hospital visits

You see a doctor and have some tests before you can take part. These include:

physical examination
blood tests
urine tests
heart trace (ECG )
MRI scan or CT scan
bone scan

You go to hospital for a check up and blood tests:

twice a week for 2 months
once a month after that

You have a CT or MRI scan, and a bone scan, about every 2 to 3 months.

When you finish treatment, you have a check up with the study team and another one a month later. They will follow you up every 3 months to see how you are getting on. They call you or they might see you at a routine hospital appointment.

You continue to have check ups and scans every 8 to 12 weeks if you stopped treatment but your cancer hasn’t got worse.

Side effects

As rucaparib is just starting to be tested in patients with prostate cancer, there might be some side effects we don’t know about yet. The study team will monitor you during the time you have treatment and you’ll have a phone number to call them if you are worried about anything.

The possible side effects of rucaparib are:

feeling or being sick
tiredness (fatigue)
taste changes
loss of appetite
changes in blood test results that measure how your liver and kidneys are working
a drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
constipation or diarrhoea
increased fat (cholesterol) levels in the blood
dizziness
itchy skin or skin rash
difficulty breathing
problems sleeping
colds
high temperatures (fever)
stomach pain
sensitivity to sunlight causing itchy or inflamed skin – the study team advise you to avoid longs periods in the sun, wear protective clothing and use sunscreen