Darolutamide + Consolidation Radiotherapy in Advanced Prostate Cancer Detected by PSMA

Cancer of Prostate Clinical Trial

— DECREASE  

Official title:

Darolutamide + Consolidation Radiotherapy in Advanced Prostate Cancer Detected by PSMA

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04319783
• Other study ID #: TROG 19.06
• Secondary ID: U1111-1242-9233
• Status: Recruiting
• Phase: Phase 2
• Start date: June 2, 2021
• Est. completion date: June 2026

Study information

• Verified date: February 2024
• Source: Trans Tasman Radiation Oncology Group
• Contact: Rebecca Montgomery
• Phone: +61 2 4014 3910
• Email: decrease[@]trog.com.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 87
• Est. completion date: June 2026
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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-a 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

Related Conditions & MeSH terms

• Advanced Prostate Carcinoma
• Cancer of Prostate
• Castrate Resistant Prostate Cancer
• Prostatic Neoplasms
• PSA

Intervention

Drug:
• Darolutamide
Darolutamide alone

Radiation:
• Radiotherapy
Darolutamide + Consolidation Radiotherapy

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Peter MacCallum Cancer Centre, Bendigo	Bendigo	Victoria
Australia	Peter MacCallum Cancer Centre, Box Hill	Box Hill	Victoria
Australia	St Vincent's Hospital	Darlinghurst	New South Wales
Australia	Townsville University Hospital	Douglas	Queensland
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	GenesisCare Hurstville	Hurstville	New South Wales
Australia	Peter MacCallum Cancer Centre, Parkville	Melbourne	Victoria
Australia	GenesisCare Fiona Stanley Hospital	Murdoch	Western Australia
Australia	Princess Alexandra Hospital (ROPART)	Raymond Terrace	Queensland
Australia	Icon Cancer Centre Epworth	Richmond	Victoria
Australia	GenesisCare North Shore	Saint Leonards	New South Wales
Australia	Western Health	St Albans	Victoria
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Australia	Princess Alexandra Hospital (ROPAIR)	Woolloongabba	Queensland
Singapore	National Cancer Centre Singapore	Singapore

Sponsors (3)

Lead Sponsor	Collaborator
Trans Tasman Radiation Oncology Group	Bayer, Peter MacCallum Cancer Centre, Australia

Countries where clinical trial is conducted

Australia,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Undetectable PSA at 12 months	Undetectable PSA at 12 months	12 months
Secondary	Radiological progression free survival	Radiological progression free survival	36 months
Secondary	Distribution of disease on baseline PSMA-PET/CT imaging	Distribution of bone, nodal, visceral and recurrent primary disease on PSMA-PET/CT	36 months
Secondary	Biochemical progression free survival	Biochemical progression free survival	36 months
Secondary	Treatment related adverse event	Treatment related adverse events (CTCAE v 5.0)	36 months
Secondary	Overall survival	Overall survival	36 months
Secondary	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