A phase III open label randomised trial of androgen deprivation therapy plus androgen receptor pathway inhibition, with or without docetaxel intensification, in metastatic hormone-sensitive prostate cancer with an unfavourable PSA response at 6 months (INTENSIFY)
Despite improvements in the management of patients with metastatic hormone sensitive prostate cancer (mHSPC), patients ultimately progress to castration resistance and die from their metastatic prostate cancer. Standard of care treatment options for mHSPC include the use of androgen deprivation therapy (ADT) and an androgen receptor pathway inhibitor (ARPI), as either a doubletÌýor with docetaxel as a triplet. We lack prospective randomised data to make this treatment choice.
Patients who fail to obtain an optimal Prostate Specific Antigen (PSA) response following 6 months of initial treatment with ADT + ARPI are known to have a poor prognosis (optimal is defined here as < 0.2 ng/ml). Evidence guiding the management of patients at this point is currently lacking, with no data to support a change, or intensification, in treatment until castration resistant cancer progression occurs. Novel approaches are needed to improve disease control, delay castration resistance and improve survival for this patient population.
INTENSIFY will test early treatment intensification with docetaxel chemotherapy in those with mHSPC and an unfavourable PSA response to an ADT + ARPI doublet at about 6 months.
Primary Objectives:
To compare the effect of treatment intensification with the addition of docetaxel to ADT + ARPI versus continuing ADT + ARPI alone on overall survival.
Secondary Objectives:
To determine the impact of treatment intensification with docetaxel on:
Translational Research Objectives:
This study will test whether it is possible to prospectively validate the Decipher Prostate Score and PTEN Inactivity Score as independent or composite, predictive biomarkers for benefit from chemotherapy using the scores as a stratification factor during randomisation.
INTENSIFY is a multi-site randomised, open label, phase III trial with 1:1 randomisation between experimental (docetaxel chemotherapy + continued ADT + ARPI) and control (continued ADT + ARPI) treatment arms for patients with metastatic hormone sensitive prostate cancer in whom the PSA remains ≥0.2 ng/ml after 5 to 8 months of treatment with an ADT + ARPI doublet.
Recruitment is intended to occur over approximately 3 years.
Following a screening period, eligible patients will be registered and randomised to either the control arm or experimental, treatment intensification arm. All patients will be followed up every 12 weeks until 24 months following randomisation of the last enrolled patient. Patients on the experimental arm will also beÌýreviewed prior to each cycle of chemotherapy and at an End of Chemotherapy Visit.
At 24 months (or at a time point determined by the TMG) following randomisation of the last enrolled patient, all patients will transfer into a Long Term Follow Up phase with remote data collection.
Consent will be obtained for long term collection of overall survival status, and subsequent anti-cancer therapy use.
In set-up
Patients with metastatic hormone sensitive prostate cancer (mHSPC) with unfavourable Prostate Specific Antigen (PSA) response following 6 months of androgen deprivation therapy (ADT) and an androgen receptor pathway inhibitor (ARPI).
This trial is funded by Prostate Cancer UK – Award Reference MA-TIA24-005, with additional support for translational endpoints from Veracyte, Inc.
Senior Trial Manager:
Anna Song / Denise Dunkley
Trial Manager:
Marina Lee
Trial Coordinator:
Mary Dahn
Trial Assistant:
Chris Chaddock
Data Manager:
Rob Waugh
Statistician:
Megan Lawrence
Ìý
Email: INTENSIFY@soton.ac.uk
Phone: 023 8120 5154
Email: ctu@soton.ac.uk
Phone: 023 8120 5154
Coming soon.
No current publications.
(University of Southampton cannot accept responsibility for external websites)
Ìý