Combining Darolutamide with Radiotherapy for Advanced Prostate Cancer

Darolutamide + Consolidation Radiotherapy in Advanced Prostate Cancer Detected by PSMA

This study is testing if combining a drug called Darolutamide with targeted radiation therapy can help people with advanced prostate cancer live longer and stay healthier.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 70 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Trans Tasman Radiation Oncology Group (Academic / other)
• Drugs / interventions: prednisone, chemotherapy
• Locations: 17 sites (Darlinghurst, New South Wales and 16 other locations)
• Trial ID: NCT04319783 on ClinicalTrials.gov

What this trial studies

This study investigates the effectiveness of combining Darolutamide, a drug known to improve survival in non-metastatic castrate resistant prostate cancer, with local consolidation radiotherapy in patients diagnosed with metastatic castrate resistant prostate cancer. The approach aims to enhance progression-free survival and overall survival by targeting limited volume metastases using stereotactic ablative body radiotherapy (SABR). The study also seeks to understand the distribution of disease at the initial diagnosis using advanced PSMA PET imaging, which is more sensitive than conventional imaging methods. This novel approach has not been previously tested in this patient population.

Who should consider this trial

Good fit: Ideal candidates include men aged 18 and older with castration-resistant prostate cancer and detectable PSMA-avid disease.

Not a fit: Patients with neuroendocrine differentiation or small cell features in their prostate cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival outcomes for patients with advanced prostate cancer.

How similar studies have performed: Previous studies in lung cancer have shown success with similar consolidation therapy approaches, suggesting potential for positive outcomes in this context.

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

Where this trial is running

Darlinghurst, New South Wales and 16 other locations

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

Study contacts

• Study coordinator: Rebecca Montgomery

Conditions Advanced Prostate Carcinoma; Cancer of Prostate; PSA; Castrate Resistant Prostate Cancer; Darolutamide; Consolidation Radiotherapy; PSMA PET; Prostate Cancer