Darolutamide + Consolidation Radiotherapy in Advanced Prostate Cancer Detected by PSMA (DECREASE)

Darolutamide is a drug that has a proven survival benefit in non-metastatic (M0) castrate resistant prostate cancer when using conventional imaging. However, it is estimated that >90% of patients have disease apparent when using PSMA PET. This study investigates the use of local consolidation radiotherapy in this cohort of men.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Prostate Carcinoma; Castrate Resistant Prostate Cancer; Cancer of Prostate; PSA
• Intervention / Treatment: Drug: Darolutamide; Radiation: Radiotherapy

Detailed Description

This study explores the use of local consolidation therapy in the setting of Darolutamide in the initial diagnosis of metastatic castrate resistant prostate cancer (mCRPC). In the chemotherapy naïve mCRPC setting, the pattern of disease is of limited volume metastases (1-5) in 34%-40% of cases. As progression at known sites of macroscopic disease is the predominant cause of failure on systemic therapies, local consolidation therapy with stereotactic ablative body radiotherapy (SABR) may improve progression free survival (PFS) and overall survival (OS). This approach has been tested in the setting of lung cancer, in which consolidation SABR has resulted in OS benefit (HR of 0.40) in phase II studies. The novel approach of local consolidation therapy has not been tested as yet in mCRPC.

The secondary objective of this study proposal is to better understand the pattern of disease distribution at first diagnosis of CRPC. Previous studies have used conventional bone scan and CT imaging, and with these investigations the proportion of patients that are 'M0' is ~35%1. However, in the new era of PSMA PET, which is far more sensitive than conventional imaging, there exists a new group of men who are M0 on conventional imaging but are M1 on PSMA PET staging.

Thus, in the DECREASE study population, we expect the vast majority of patients with conventionally imaged 'M0 CRPC' will have disease detectable on PSMA PET scanning. In this context, the central hypothesis of this trial is that the addition of consolidation radiotherapy to darolutamide to PSMA detected sites of disease will improve the clinical outcome of patients compared to those patients receiving darolutamide alone.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2101
      • St Vincent's Hospital
    • Hurstville, New South Wales, Australia, 2220
      • GenesisCare Hurstville
    • Saint Leonards, New South Wales, Australia, 2065
      • Genesiscare North Shore
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle
  • Queensland
    • Herston, Queensland, Australia, 4006
      • Royal Brisbane and Women's Hospital
    • Raymond Terrace, Queensland, Australia, 4101
      • Princess Alexandra Hospital (ROPART)
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital (ROPAIR)
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital
  • Victoria
    • Bendigo, Victoria, Australia, 3550
      • Peter MacCallum Cancer Centre, Bendigo
    • Box Hill, Victoria, Australia, 3128
      • Peter MacCallum Cancer Centre, Box Hill
    • Melbourne, Victoria, Australia, 3002
      • Peter MacCallum Cancer Centre, Parkville
    • Richmond, Victoria, Australia, 3121
      • Icon Cancer Centre Epworth
    • St Albans, Victoria, Australia, 3021
      • Western Health
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • GenesisCare Fiona Stanley Hospital
• Singapore
  • Singapore, Singapore, 168583
    • National Cancer Centre Singapore

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥ 18 years of age and provided written Informed Consent
• Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
• Castration-resistant prostate cancer, defined as at least 2 consecutive PSA rises obtained at least 1 week apart in the setting of castrate testosterone levels
• Castrate level of serum testosterone (<1.7 nmol/l [50 ng/dl]) on gonadotrophin - releasing hormone (GnRH) agonist or antagonist therapy or after bilateral orchiectomy
• A baseline PSA level of at least 1ng per millilitre and a PSA doubling time of 10 months or less
• Adequate bone marrow reserve and organ function Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• At least 1 site of PSMA-avid disease on PSMA-PET/CT imaging in any of the following regions; At least 1 site of PSMA-avid disease on PSMA-PET/CT imaging in any of the following regions:

  • Local recurrence within the prostate gland or prostate bed
  • Regional lymph node disease (below the aortic bifurcation)
  • Extra-pelvic lymph node, bone or soft tissue metastatic disease

Exclusion Criteria:

• Patients with detectable metastases or a history of metastatic disease on conventional imaging
• Prior treatment with second-generation androgen receptor (AR) antagonists, CYP17 enzyme inhibitors or oral ketoconazole
• Use of oestrogens or 5-α reductase inhibitors or anti-androgens within 28 days before randomisation
• Use of systemic corticosteroid with a dose greater than the equivalent 10 mg of prednisone/day within 28 days before randomisation
• Radiotherapy within 12 weeks prior to randomisation
• Initiation of treatment with an osteoclast-targeted therapy to prevent skeletal-related events within 12 weeks before randomisation
• Any of the following within 6 months before randomisation: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft; congestive heart failure New York Heart Association (NYHA) Class III or IV
• Uncontrolled hypertension
• Prior malignancy
• Gastrointestinal disorder or procedure that expects to interfere significantly with the absorption of study treatment
• Unable to swallow study medications and comply with study requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Darolutamide; Darolutimide 600mg BD	Drug: Darolutamide; Darolutamide alone; Other Names: NUBEQA, Bayer HealthCare Pharmaceuticals Inc.
Experimental: Local consolidation Radiotherapy + Darolutamide; Darolutimide 600mg BD + local consolidative radiotherapy, with a biological equivalent dose of 30Gy/10fx or greater if delivered with SABR. SABR is the preferred treatment approach, however conventional radiotherapy is acceptable. To up to 5 sites of disease	Drug: Darolutamide; Darolutamide alone; Other Names: NUBEQA, Bayer HealthCare Pharmaceuticals Inc.; Radiation: Radiotherapy; Darolutamide + Consolidation Radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Undetectable PSA at 12 months	Undetectable PSA at 12 months	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiological progression free survival	Radiological progression free survival	36 months
Distribution of disease on baseline PSMA-PET/CT imaging	Distribution of bone, nodal, visceral and recurrent primary disease on PSMA-PET/CT	36 months
Biochemical progression free survival	Biochemical progression free survival	36 months
Treatment related adverse event	Treatment related adverse events (CTCAE v 5.0)	36 months
Overall survival	Overall survival	36 months
Patterns of disease on PSMA PET/CT after 12 weeks of commencing Darolutamide, and at time of disease progression	PSMA avid disease at irradiated site / unirradiated site / bone / local / nodal / visceral	3 months

Collaborators and Investigators

• Sponsor: Trans Tasman Radiation Oncology Group
• Collaborators: Bayer; Peter MacCallum Cancer Centre, Australia
• Investigators: Study Chair: Shankar Siva, Peter MacCallum Cancer Centre, Australia; Study Chair: Arun Azad, Peter MacCallum Cancer Centre, Australia

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: March 9, 2020
• First Submitted That Met QC Criteria: March 22, 2020
• First Posted (Actual): March 24, 2020

Study Record Updates

• Last Update Posted (Actual): August 21, 2025
• Last Update Submitted That Met QC Criteria: August 19, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: PSA; Prostate Cancer; PSMA PET; Darolutamide; Consolidation Radiotherapy; Advanced Prostate Cancer
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: TROG 19.06; U1111-1242-9233 (Other Identifier: UTN- World Health Organisation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No