Darolutamide + Consolidation Radiotherapy in Advanced Prostate Cancer Detected by PSMA

NCT ID: NCT04319783

Last Updated: 2025-08-21

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-02
• Study Completion Date: 2026-06-30

Brief Summary

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.

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.

Conditions

Advanced Prostate Carcinoma; Cancer of Prostate; PSA; Castrate Resistant Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Darolutamide

Darolutimide 600mg BD

Group Type: EXPERIMENTAL

Darolutamide

Intervention Type: DRUG

Darolutamide alone

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

Group Type: EXPERIMENTAL

Darolutamide

Intervention Type: DRUG

Darolutamide alone

Radiotherapy

Intervention Type: RADIATION

Darolutamide + Consolidation Radiotherapy

Interventions

Darolutamide

Darolutamide alone

Intervention Type: DRUG

Radiotherapy

Darolutamide + Consolidation Radiotherapy

Intervention Type: RADIATION

Other Intervention Names

NUBEQA, Bayer HealthCare Pharmaceuticals Inc.

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

Peter MacCallum Cancer Centre, Australia

OTHER

Sponsor Role: collaborator

Trans Tasman Radiation Oncology Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shankar Siva

Role: STUDY_CHAIR

Peter MacCallum Cancer Centre, Australia

Arun Azad

Role: STUDY_CHAIR

Peter MacCallum Cancer Centre, Australia

Locations

St Vincent's Hospital

Darlinghurst, New South Wales, Australia

GenesisCare Hurstville

Hurstville, New South Wales, Australia

GenesisCare North Shore

Saint Leonards, New South Wales, Australia

Calvary Mater Newcastle

Waratah, New South Wales, Australia

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Princess Alexandra Hospital (ROPART)

Raymond Terrace, Queensland, Australia

Princess Alexandra Hospital (ROPAIR)

Woolloongabba, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Royal Hobart Hospital

Hobart, Tasmania, Australia

Peter MacCallum Cancer Centre, Bendigo

Bendigo, Victoria, Australia

Peter MacCallum Cancer Centre, Box Hill

Box Hill, Victoria, Australia

Peter MacCallum Cancer Centre, Parkville

Melbourne, Victoria, Australia

Icon Cancer Centre Epworth

Richmond, Victoria, Australia

Western Health

St Albans, Victoria, Australia

GenesisCare Fiona Stanley Hospital

Murdoch, Western Australia, Australia

National Cancer Centre Singapore

Singapore, , Singapore

Countries

Australia; Singapore

Other Identifiers

U1111-1242-9233

Identifier Type: OTHER

Identifier Source: secondary_id

TROG 19.06

Identifier Type: -

Identifier Source: org_study_id