Randomized Phase II Trial on Short Term Darolutamide Concomitant to Radiation Therapy for Patients With Intermediate Unfavorable Risk Prostate Cancer

Prior treatment

• Previous prostate cancer treated by androgen deprivation, chemotherapy, surgery, or radiotherapy,
• Patients with previous orchiectomy
• Patients actively receiving or having received within 6 months prior enrollment any concurrent androgens, anti-androgens, estrogens, or progestational agents,
• Patients having received ketoconazole, finasteride or dutasteride within 30 days of inclusion,
• Previous and current malignancies other than prostate cancer within the last 5 years with the exception of adequately treated basal cell or squamous cell carcinoma of the skin, acute lymphoblastic leukemia, non-muscle invasive bladder cancer,
• Major surgery within 4 weeks prior enrolment except pelvic lymph-nodes dissection,
• Men who are not using an effective method of contraception as previously described

Other illness

• Stage T3b-T4 prostate cancer by clinical examination or radiologic evaluation,
• Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection),
• History of cerebrovascular accident (within the last 6 months)
• Impaired cardiac function as defined in the Protocol
• Uncontrolled hypertension
• Impairment of gastrointestinal function or GI disease that may significantly alter the absorption of study drug,
• Known hypersensitivity to any involved study drug or of its formulation components, to natural gonadotrophin releasing hormone or its analogues
• History of non-compliance to medical regimens or inability to grant consent,

Lab values

• Hypogonadism or severe androgen deficiency as defined by screening serum testosterone less than 50 ng/dL or below the normal range for the institution.
• Galactose intolerance, total lactase deficiency or glucose-galactose malabsorption syndrome

Other

• Patients with Gleason score ≥8,
• Patients with PSA \>20 ng/ml,
• Presence of loco-regional or distant metastasis,
• Contra-indications to MRI and to contrast-enhanced CT-scan,
• Use of herbal or alternative remedies that may affect hormonal status such as Prostasol or PC-SPES,
• Patient unable to follow and comply with the study procedures because of any geographical, social or psychpsychological reasons,
• Individuals under judicial protection or deprived of liberty.
• Inability to swallow or to give subcutaneous or intramuscular injections.

• Age ≥ 18,
• Histological diagnosis of prostate malignancy cancer
• Cancer without loco-regional or distant metastasis (tumor assessment must comprise at least Pelvic MRI AND thoraco-abdomino-pelvic contrast-enhanced CT-Scan AND Bone Scintigraphy. (Note that additional assessment by PET-Scan is allowed as per investigator judgement),
• Unfavorable intermediate risk prostate cancer diagnosis defined by the NCCN Guidelines.
  • One of the following criteria is sufficient to define an unfavorable intermediate risk prostate cancer:
  • Gleason = 7 (4+3)
  • ≥ 50% of thecore of biopsies need to be positive for adenocarcinoma
  • If these criteria are not being identified, two or three of the following criteria are necessary to define unfavorable intermediate risk prostate cancer:
  • PSA value between 10-20 ng/ml
  • Gleason 7 (3+4) or 6
  • T2b (clinical or radiological) Note: patients with iT3a can be included only if gleason score is 6 and PSA less than 20 .
• Patients newly diagnosed with an unfavorable intermediate risk prostate cancer according to the protocol criteria or previously diagnosed with low risk (Gleason score \< 6, clinical stage \< T2a, and PSA\< 10) prostate cancer progressing to eligible risk disease according to the protocol criteria within 30 days before registration
• Patients must have a life expectancy of at least 5 years,
• Performance status ECOG ≤ 2,
• Patients without contra-indications to EBRT as per physician judgement,
• Patients with adequate organ function defined by all the following laboratory values
• Available archived paraffin-embedded tumor sample for research purpose,
• Patients with a social security in compliance with the french law,
• Voluntary signed and dated written informed consent prior to any study specific procedure,
• Men must agree to use an effective method of contraception throughout the treatment period and for one week after discontinuation of treatment.