Title

INTENSIFY: A phase III open label randomised trial of androgen deprivation therapy plus androgen receptor pathway inhibition, with or without docetaxel intensification, in metastatic prostate cancer with a PSA ≥0.2 ng/ml at 6 months.

Description

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 doublet or 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.

Objectives

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:

• PSA Progression Free survival (PFS)
• Clinical Progression free survival (cPFS)
• Adverse event profiles
• Health related quality of life
• Cost-effectiveness
• Overall survival compared to standard therapy with respect to Decipher prostate score
• Overall survival compared to standard therapy with respect to PTEN Inactivity Score
• Overall survival compared to standard therapy with respect to a composite of Decipher Prostate and PTEN Inactivity Scores

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.

Trial Design