ACE: testing a new drug for the PTEN-deficient men

What they want to find out

Research has begun to deliver new ways to treat advanced prostate cancer, but we still don’t have enough weapons in our arsenal to beat it. We need to improve our understanding of the genes that drive advanced prostate cancer, and how these genes vary between each man.

A common gene to be altered in men with advanced prostate cancer is called PTEN. Men with a fault in this gene often find that treatments like abiraterone and enzalutamide don’t work very well for them. Previous research suggests that this may be because PTEN-mutated prostate cancers can ‘hide’ from the immune system, stopping it from fighting the cancer. This can also promote resistance to treatments.

In this study Professor David Waugh and Professor Johann de Bono are investigating a potential new treatment for men with PTEN-mutated prostate cancers which could restore the immune system back to full power against prostate cancer.

How they’re going about it

The researchers are combining laboratory and clinical work to test their potential new drug.

First, they want to understand about the basic biology of the drug, and see whether it works in the way they expect it to. They’re testing what happens to the immune system, cancer cell growth, overall tumour size and survival when they use a drug in PTEN-mutated mice. They’re also investigating whether treating the mice with abiraterone at the same time makes any difference to how well this new type of treatment works.

The team are also conducting two trials in men to test the drug. The first is to test how safe this drug is for men. Then they’ll run a second, bigger study to see whether treatment with this new drug can enhance the effect of enzalutamide in men with advanced prostate cancer, so it works better for them for longer.

Throughout these clinical tests, the research team will collect blood and biopsy tissue from the patients, so that they can look back to see whether the men who respond best to the combination of enzalutamide and the new drug are those patients with a mutation in the PTEN gene. This would imply that this combination would be an appropriate first choice for these men.

Progress so far

So far, the team have completed their first trial, and shown that patients who received the drug in combination with Enzalutamide had no serious side effects. Now, the team is moving on to test the drug at a higher dose in combination with Enzalutamide.

The researchers are also continuing to carrying out work in the lab to explore further how the drug works.

This trial is still looking for men to take part. You can read the information below to see if you may be suitable to take part in this study, and contact your medical team for full details on whether you can take part.

If you’d like support with deciding whether taking part in a clinical trial is right for you, you can speak to your medical team or contact our Specialist Nurses on 0800 074 8383.

Who can take part

You may be eligible to take part in this study if you have:

• Metastatic castration resistant prostate cancer.
• PSA ≥ 10ng/ml.
• Received prior castration by orchiectomy and/or ongoing luteinizing hormone releasing hormone agonist treatment.
• Ongoing androgen deprivation with serum testosterone < 50 ng/dL (<2.0 nM).
• All efforts should be made to discontinue steroid usage but up-to 5mg BD prednisolone (or equivalent) will be allowed.

Who can’t take part

You would not be eligible to take part if you have:

• Had surgery, chemotherapy or other anti-cancer therapy within 4 weeks prior to trial entry/randomization into the study. Any other therapy for prostate cancer, other than gonadotropin releasing hormone analogue therapy, such as progesterone, medroxyprogesterone, progestins or 5-alpha reductase inhibitors, must be discontinued at least 2 weeks before the first dose of the study drug.
• Participation in another clinical trial and any concurrent treatment with any investigational drug within 4 weeks prior to trial entry.
• Prior limited field radiotherapy within 2 weeks and wide field radiotherapy within 4 weeks prior to trial entry.
• Clinical and/or biochemical evidence of hyperaldosteronism or hypopituitarism.
• History of seizures or other predisposing factors including, but not limited to, underlying brain injury, stroke, primary brain tumours, brain metastases and leptomeningeal disease, or alcoholism.

For full inclusion and exclusion criteria speak to your medical team.

Where the trial is taking place

• The Royal Marsden, Downs Rd, Sutton SM2 5PT, UK
• Belfast City Hospital, 51 Lisburn Rd, Belfast BT9 7AB, UK

We try to keep this information as up to date as possible, but there may be times when study details have changed and we haven’t updated our web information. Speak to your medical team, or our Specialist Nurses, for the most up to date information on prostate cancer clinical studies.