Treatment with darolutamide +/- radiation therapy for patients with a castration resistant cancer and metastases detected by functional imaging

Prior treatment

• Patient previously treated for metastatic castrate-resistant prostate cancer with chemotherapy or immunotherapy. Patients who received prior NHA are eligible provided: - they did not progress on previous NHA - they progressed on previous NHA and chemotherapy is not indicated by investigator
• Inability and/or difficulty to swallow oral medications.
• 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.
• Patients participating in another therapeutic trial within the 30 days prior to randomisation.

Other illness

• A history of cancer, other than the prostate cancer under study, within the 3 years prior to study inclusion, excluding cured localised cancer such as non-melanomatous skin cancer and non-muscle invasive bladder cancer.
• Presence of an uncontrolled disease or affection that according to the investigator will hinder compliance with the trial procedures or requires hospitalisation.
• Known to have active viral hepatitis, active human immunodeficiency virus (HIV) or chronic liver disease at screening
• Patients with known allergy or severe hypersensitivity to the study treatment or any of its excipients.
• Gastrointestinal disorder or procedure that can be expected to interfere significantly with the absorption of study treatment.

Other

• Patients unable to comply with trial obligations for geographic, social, or physical reasons, or who are unable to understand the purpose and procedures of the trial.
• Person deprived of their liberty or under protective custody or guardianship.

• Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient’s consent.
• Albumin >2.5 g/dL
• Systolic blood pressure <160 mmHg and diastolic blood pressure <100 mmHg, as documented at baseline. Patients with hypertension are eligible if their hypertension is controlled and they meet all other eligibility criteria.
• Adequate kidney function with a creatinine clearance >30 mL/min (Cockcroft-Gault).
• Patient with Eastern Cooperative Oncology group (ECOG) performance status (PS) ≤1.
• Patient is willing to use contraceptive during and for at least 1 week after discontinuing darolutamide.
• Patient affiliated to the social security system (or equivalent according to local regulations for participation in clinical trials).
• Patient is willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up.
• Patients aged ≥18 years.
• Patient with histologically confirmed of adenocarcinoma prostate cancer without small cell or pure endocrine features.
• Patient with a history of local treatment with curative intent for localised prostate cancer, including surgery or radiotherapy.
• Patients with castration resistant prostate cancer, defined with with a combination of Castrate level of testosterone: testosterone < 50ng/dl or 1.7 nmol/L. AND at least one of the following conditions: An increasing PSA level, confirmed in 3 consecutive assessments performed at least 1 week apart despite androgen deprivation therapy; • Tumour progression of soft tissue according to the response criteria in solid tumours (RECIST) version (v)1.1; • Tumour progression on bone scan, according to PCWG3 criteria.
• Detection of 1 to 5 metastatic sites (pelvic lymph nodes included) on new generation PET using either choline, fluciclovine, or PSMA as tracer;
• All metastatic sites must be amenable to stereotactic radiation therapy.
• Patient with normal haematological function: absolute neutrophil count (ANC) >1.0 x 10^9/L, platelets count ≥100 x 10^9/L, and haemoglobin ≥9.0 g/dL.
• Patient with normal liver function with total bilirubin ≤1.5 upper limit of normal (ULN) (unless documented Gilbert’s syndrome), ASAT and ALAT ≤2.5 ULN (≤5 ULN in the presence of liver metastases).