New trial aims to improve treatment for advanced prostate cancer

Researchers will see if selecting patients who may need more intensive treatment can improve outcomes for advanced prostate cancer.

The aim is to improve survival by delaying the progression of cancer that has spread to other parts of the body (metastatic cancer).

The INTENSIFY trial is led by researchers at University Hospital Southampton (UHS), the Southampton Clinical Trials Unit (SCTU), UCL and the University of Glasgow. It is funded by a £1.9m grant from Prostate Cancer UK.

The trial, which is sponsored by UHS, will recruit over 500 patients at around 20 hospital sites across the UK. It is currently in set-up and is due to open to patients in the new year.

Preventing men's cancer deaths

Prostate cancer is the most common cancer in men in the UK. One in eight men are likely to be diagnosed with the disease during their lifetime.

Survival for the disease, especially when diagnosed in its early stages, is generally good. Eight in 10 patients survive for over a decade after their diagnosis.

However, when the cancer becomes metastatic and spreads to other parts of the body, it becomes incurable. There are still around 12,000 prostate cancer deaths in the UK every year.

The initial treatment for most men with metastatic prostate cancer is a combination of two hormone treatments. This is known as doublet therapy.

These treatments reduce the amount of testosterone produced by the body, and also block its effects. This helps to slow the growth of the cancer.

Patients are monitored using a blood test for prostate specific antigen (PSA). This indicates whether the cancer is responding to treatment.

Optimising treatment timing

Professor Simon Crabb is leading the INTENSIFY trial. This aims to try and establish the best timing for these treatments in patients with high-risk metastatic prostate cancer.

He is Professor of Experimental Cancer Therapeutics at the University of Southampton. He is also Honorary Consultant of Medical Oncology at UHS and an Associate Clinical Director at the SCTU.

“Most patients will see a reduction in their PSA after starting hormone therapy,” he says. “But if the PSA remains at a higher level after six months of treatment, this indicates poorer long-term outcomes, including survival.”

“There is evidence that adding chemotherapy early on could prevent further cancer growth. However, chemotherapy will mean more, potentially unpleasant, side effects for patients which can affect their quality of life.”

Trialling a triple therapy

Patients whose PSA levels indicate that their cancer may not be responding as well to doublet hormone treatment will take part.

Patients will be randomly assigned to one of two groups. Those assigned to the control group will continue with the standard hormone treatment. Those in the intervention group will have the standard treatment plus a chemotherapy drug called docetaxel.

Every patient will be closely monitored to see how their cancer responds and the side effects they experience.

Patients may be offered other standard treatments if their cancer gets worse. These patients will continue to be included in the trial.

Making treatment more personalised

The trial also aims to build on novel insights, made by Professor Gert Attard at UCL. These suggest we may be able to select which prostate cancers are sensitive to chemotherapy, based on patterns in the genes that they express.

The team are collaborating with a global diagnostics company called Veracyte. The company will analyse tumour samples taken from the INTENSIFY participants. They will use the Decipher Prostate Genomic Classifier to test these gene expression patterns.

Professor Attard said: “Prostate Cancer UK had funded discovery of novel molecular biomarkers, or genetic clues, that predict when chemotherapy will work.

"A really exciting part of this trial, also funded by Prostate Cancer UK, is that we will formally test whether patients identified by these biomarkers live significantly longer when given chemotherapy. These could then become established for use for all patients.”

The trial is being funded by Prostate Cancer UK as part of its Transformational Impact Awards.

Simon Grieveson is Assistant Director of Research at Prostate Cancer UK.

“We’re thrilled to be funding this groundbreaking trial, building on our history of supporting cutting-edge research to improve and personalise men’s prostate cancer treatment,” he said.

“For men with metastatic prostate cancer, it’s hard to predict who will respond well to hormone therapy and who may need additional treatment, such as chemotherapy.

“INTENSIFY will show us whether we can reserve this more intensive treatment combination for those who are most likely to benefit, whilst delaying the use of chemotherapy in others who are responding well to their hormone therapy.

“Central to all of this is our aim to reduce harmful side-effects and improve men’s quality of life and the time they can spend with family and friends.

"At Prostate Cancer UK, we’ve invested over £120 million into research into the most common cancer in men, particularly towards developing more personalised treatment approaches tailored to every man and their prostate cancer. INTENSIFY is the next step on this journey, and we’re really looking forward to seeing the results of the trial.”