Last updated on July 2020

Darolutamide Augments Standard Therapy for Localised Very High-Risk Cancer of the Prostate


Are you eligible to participate in this study?

You may be eligible for this study if you meet the following criteria:

  • Conditions: Prostatic disorder | Early | Prostate Disorders | Malignant neoplasm of prostate | Recurrent | Prostate Cancer
  • Age: Between 18 - 100 Years
  • Gender: Male

Inclusion Criteria:

  1. Men aged 18 years and older, with pathological diagnosis of adenocarcinoma of the prostate
  2. EITHER planned for primary RT and judged to be at very high risk for recurrence based on any of the following:
    • Grade Group 5, OR
    • Grade Group 4 AND one or more of the following: clinical T2b-4 OR MRI with seminal vesicle invasion OR extracapsular extension OR PSA > 20ng/mL, OR
    • Pelvic nodal involvement (involvement of lymph nodes (LNs) at or below the bifurcation of the common iliac arteries) defined radiologically as greater than 10mm on short axis using standard CT or MRI, or pathologically confirmed (PSMA PET alone is not considered enough if < 10mm)

OR Post-radical prostatectomy 365 days prior to randomisation and planned for RT with persistent PSA ( 0.1 ng/mL which has not fallen on two occasions at least one week apart) or rising PSA (PSA > 0.1 ng/mL and rising on two occasions at least one week apart) judged to be at very high risk for recurrence based on any of the

following
  • Grade Group 5, OR
  • Grade Group 4 AND pT3a or higher, OR
  • Pelvic nodal involvement (involvement of LNs at or below the bifurcation of the common iliac arteries) defined radiologically as greater than 10mm on short axis using standard CT or MRI, or pathologically confirmed (PSMA PET alone is not considered enough if 10mm) 3. Adequate bone marrow function: Haemoglobin 100g/L, white cell count (WCC) 4.0x10^9/L, absolute neutrophil count (ANC) 1.5x10^9/L and platelets > 100 x 10^9/L 4. Adequate liver function: alanine aminotransferase (ALT) < 2 x upper limit of normal (ULN) and total bilirubin < 1.5 x ULN, (or if total bilirubin is between 1.5 - 2 x ULN, they must have a normal conjugated bilirubin) 5. Adequate renal function: calculated creatinine clearance > 30 mL/min (Cockroft-Gault) 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1 7. Study treatment both planned and able to start within 7 days after randomisation 8. Willing to complete health-related quality of life (HRQL) questionnaires UNLESS is unable to complete because of literacy or limited vision 9. Willing and able to comply with all study requirements, including standard of care treatment such as EBRT, timing and/or nature of required assessments 10. Signed, written informed consent

Exclusion Criteria:

11. Prostate cancer with predominant non-adenocarcinoma features (sarcomatoid or spindle cell or neuroendocrine small cell or squamous cell components or other non-adenocarcinoma)

12. Involvement of LNs by conventional CT imaging superior to the common iliac artery bifurcation, and/or outside the pelvis (distant LNs). LN involvement is defined by histopathological confirmation, or by a short axis measurement >10mm on standard imaging (CT or MRI, but not PET).

13. Evidence of metastatic disease per RECIST criteria: the minimum imaging required is a CT and/or MRI of the abdomen and pelvis, and a whole body radioisotope bone scan (WBBS). If equivocal bone scan, follow-up plain films are required to show NO evidence of cancer if not covered by CT/MRI. If PSMA PET shows disease beyond the pelvic LN not seen on conventional imaging per RECIST, the patient is still eligible.

14. PSA > 100 ng/mL

15. Any prior use of new generation potent androgen receptor inhibition (abiraterone, enzalutamide, apalutamide, darolutamide or similar agents).

16. Prior ADT except the following, which are allowed:

  • Prior androgen deprivation commenced within 90 days prior to randomisation as long as it is limited to: (i) LHRHA, or (ii) low potency nonsteroidal antiandrogen (NSAA) (e.g bicalutamide, flutamide, nilutamide);
  • Any prior use of 5-alpha reductase inhibitor 17. Bilateral orchidectomy 18. Prior pelvic brachytherapy or other radiotherapy that would result in an overlap of radiotherapy fields that would preclude the required RT 19. History of
  • Loss of consciousness or transient ischemic attack within 3 months prior to randomisation, or
  • Significant cardiovascular disease within 3 months prior to randomisation: including myocardial infarction, unstable angina, congestive heart failure (NYHA grade II or greater), ongoing arrhythmias of Grade > 2 (CTCAE v5.0), thromboembolic events (e.g. deep vein thrombosis, pulmonary embolism). Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed. 20. Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of darolutamide, including difficulty swallowing tablets 21. History of another malignancy within 5 years prior to randomisation except for those malignancies treated with curative intent with a predicted risk of relapse of less than 10% including but not limited to non-melanoma carcinoma of the skin; or adequately treated, non-muscle-invasive urothelial carcinoma of the bladder (i.e. Tis, Ta and low grade T1 tumours). All such cases are to be discussed with study chairs and rationale for decision documented. 22. Concurrent illness, including severe infection that might jeopardise the ability of the participant to undergo the procedures outlined in this protocol with reasonable safety (HIV infection is not an exclusion criterion if it is controlled with anti-retroviral drugs that are unaffected by concomitant darolutamide) 23. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse 24. Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception 25. Participation in other clinical trials of investigational agents for the treatment of prostate cancer or other diseases 26. Major surgery within 21 days prior to randomisation

Recruitment Status: Open


Brief Description Eligibility Contact Research Team


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