Clinical trial NCT04319783: Darolutamide + Consolidation Radiotherapy in Advanced Prostate Cancer Detected by PSMA
Official title: Darolutamide + Consolidation Radiotherapy in Advanced Prostate Cancer Detected by PSMA
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Advanced Prostate Carcinoma
Cancer of Prostate
PSA
Castrate Resistant Prostate Cancer
Keywords: Darolutamide
Consolidation Radiotherapy
PSA
PSMA PET
Prostate Cancer
Advanced Prostate Cancer
Lead sponsor: Trans Tasman Radiation Oncology Group
Sponsor class: OTHER
Collaborators: name: Bayer
name: Peter MacCallum Cancer Centre, Australia
First posted: 2020-03-24
Enrollment: 70
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Undetectable PSA at 12 months
timeFrame: 12 months
Secondary outcomes:
measure: Radiological progression free survival
timeFrame: 36 months
measure: Distribution of disease on baseline PSMA-PET/CT imaging
timeFrame: 36 months
measure: Biochemical progression free survival
timeFrame: 36 months
measure: Treatment related adverse event
timeFrame: 36 months
measure: Overall survival
timeFrame: 36 months
measure: Patterns of disease on PSMA PET/CT after 12 weeks of commencing Darolutamide, and at time of disease progression
timeFrame: 3 months
Other outcomes:
Locations:
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital
state: New South Wales
city: Hurstville
country: Australia
facility: GenesisCare Hurstville
state: New South Wales
city: Saint Leonards
country: Australia
facility: GenesisCare North Shore
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Douglas
country: Australia
facility: Townsville University Hospital
state: Queensland
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Raymond Terrace
country: Australia
facility: Princess Alexandra Hospital (ROPART)
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital (ROPAIR)
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Bendigo
country: Australia
facility: Peter MacCallum Cancer Centre, Bendigo
state: Victoria
city: Box Hill
country: Australia
facility: Peter MacCallum Cancer Centre, Box Hill
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre, Parkville
state: Victoria
city: Richmond
country: Australia
facility: Icon Cancer Centre Epworth
state: Victoria
city: St Albans
country: Australia
facility: Western Health
state: Victoria
city: Murdoch
country: Australia
facility: GenesisCare Fiona Stanley Hospital
state: Western Australia
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
Study officials:
affiliation: Peter MacCallum Cancer Centre, Australia
name: Shankar Siva
role: STUDY_CHAIR
affiliation: Peter MacCallum Cancer Centre, Australia
name: Arun Azad
role: STUDY_CHAIR
References: