Darolutamide + Consolidation Radiotherapy in Advanced Prostate Cancer Detected by PSMA

  • STATUS
    Recruiting
  • End date
    Jun 8, 2026
  • participants needed
    87
  • sponsor
    Trans Tasman Radiation Oncology Group
Updated on 8 September 2021

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 nave 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.

Details
Condition prostate carcinoma, Prostate Cancer, Early, Recurrent, Malignant neoplasm of prostate, psa level, Castrate Resistant Prostate Cancer, prostate cancers, prostate specific antigen (psa), PROSTATE SPECIFIC ANTIGEN, Prostate Cancer, Advanced Prostate Carcinoma, prostate-specific antigen
Treatment Radiotherapy, Darolutamide
Clinical Study IdentifierNCT04319783
SponsorTrans Tasman Radiation Oncology Group
Last Modified on8 September 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Males aged 18 years or older
Has provided written Informed Consent for participation in this trial
Histological or cytologically confirmed adenocarcinoma of prostate without neuroendocrine differentiation or small cell features
Castration-resistant prostate cancer (CRPC) defined as at least 2 consecutive PSA rises obtained at least 1 week apart in the setting of castrate testosterone levels (see below). If the patient has a history of anti-androgen use and recent withdrawal, the most recent PSA value must be obtained at least 4 weeks after anti-androgen withdrawal
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. Patients who have not undergone bilateral orchiectomy must continue GnRH therapy during the study
A baseline PSA level of at least 2ng per millilitre and a PSA doubling time of 10 months or less
An ECOG performance status score of 0 or 1
Blood counts at screening: haemoglobin 9.0 g/dl, absolute neutrophil count 1500/l (1.5109/l), platelet count 100,000/l (100109/l) (patient must not have received any growth factor or blood transfusion within 7 days of the haematology laboratory obtained at screening)
Screening values of serum alanine transaminase (ALT) and aspartate transaminase (AST) 2.5 x upper limit of normal (ULN), total bilirubin 1.5 x ULN (except patients with a diagnosis of Gilbert's disease), creatinine 2.0 x ULN
At least 1 site of PSMA-avid disease on PSMA-PET 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 (whole body bone scan and computed tomography (CT) of the pelvis, abdomen and chest). NOTE: Presence of pelvic lymph nodes <2 cm in short axis below the aortic bifurcation is allowed
Prior treatment with: (1) second-generation androgen receptor (AR) antagonists such as enzalutamide and apalutamide, or darolutamide or other investigational AR antagonists; (2) CYP17 enzyme inhibitors, such as abiraterone acetate and orteronel; or (3) oral ketoconazole
Use of estrogens or 5- reductase inhibitors (finasteride, dutasteride) or anti-androgens (bicalutamide, flutamide, nilutamide, cyproterone acetate) 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
Radiation therapy (external beam radiation therapy [EBRT], brachytherapy, or radiopharmaceuticals) within 12 weeks prior to randomisation
Initiation of treatment with an osteoclast-targeted therapy (bisphosphonate or denosumab) to prevent skeletal-related events within 12 weeks before randomisation. NOTE: Patients receiving osteoclast-targeted therapy to prevent bone loss at a dose and schedule indicated for osteoporosis may continue treatment at the same dose and schedule, providing it was commenced at least 28 days 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 as indicated by a systolic blood pressure 160 mmHg or diastolic blood pressure 100 mmHg at screening
Prior malignancy. NOTE: Adequately treated basal cell or squamous cell carcinoma of skin or superficial bladder cancer that has not spread behind the connective tissue layer (i.e., pTis, pTa, and pT1) is allowed, as well as any other cancer for which the last anti-cancer therapeutic intervention has been completed - 5 years ago and from which the patient has been disease-free
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
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