Study: NCT06625970

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Darolutamide
Description: Pharmaceutical form: 300 mg tablets Administration route: oral (PO) Posology: 600 mg twice daily (BID)

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Darolutamide
Description: Pharmaceutical form: 300 mg tablets Administration route: oral (PO) Posology: 600 mg twice daily (BID)

Intervention type: RADIATION
Group type: EXPERIMENTAL
Intervention: Stereotactic Body RadioTherapy (SBRT)
Description: Following randomization, patients will receive dose escalated intensity modulated radiotherapy (IMRT) using normo-fractionation or moderate hypo-fractionation including whole pelvic nodal radiotherapy (WPRT).~At study entry, each investigational site will be asked to choose one regimen (normo-fractionation or moderate hypo-fractionation) which will be applied for all patients included by the investigational site in the study.~SBRT, experimental treatment, will be used as a boost in Arms C \& D. The placement of 3 to 4 fiducial markers for stereotactic boost is mandatory.~SBRT will be applied only on Prostate: 2 times 10 Gy delivered to the prostate with a gap of one week between each SBRT fraction.

Intervention type: RADIATION
Group type: EXPERIMENTAL
Intervention: Stereotactic Body RadioTherapy (SBRT)
Description: Following randomization, patients will receive dose escalated intensity modulated radiotherapy (IMRT) using normo-fractionation or moderate hypo-fractionation including whole pelvic nodal radiotherapy (WPRT).~At study entry, each investigational site will be asked to choose one regimen (normo-fractionation or moderate hypo-fractionation) which will be applied for all patients included by the investigational site in the study.~SBRT, experimental treatment, will be used as a boost in Arms C \& D. The placement of 3 to 4 fiducial markers for stereotactic boost is mandatory.~SBRT will be applied only on Prostate: 2 times 10 Gy delivered to the prostate with a gap of one week between each SBRT fraction.

Intervention type: DRUG
Group type: OTHER
Intervention: ADT (Standard of Care)
Description: Androgen Deprivation Therapy (ADT)~The ADT treatment will be chosen at the investigator's discretion, and will be administered according to local standard procedures for up to 2 years.~Patients who may have received ADT prior joining the study should have started the ADT treatment within a maximum of 6 weeks before randomization. Otherwise ADT will be started on Day 1 (or 14 days at the latest after the randomization).

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: ADT (Standard of Care)
Description: Androgen Deprivation Therapy (ADT)~The ADT treatment will be chosen at the investigator's discretion, and will be administered according to local standard procedures for up to 2 years.~Patients who may have received ADT prior joining the study should have started the ADT treatment within a maximum of 6 weeks before randomization. Otherwise ADT will be started on Day 1 (or 14 days at the latest after the randomization).

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: ADT (Standard of Care)
Description: Androgen Deprivation Therapy (ADT)~The ADT treatment will be chosen at the investigator's discretion, and will be administered according to local standard procedures for up to 2 years.~Patients who may have received ADT prior joining the study should have started the ADT treatment within a maximum of 6 weeks before randomization. Otherwise ADT will be started on Day 1 (or 14 days at the latest after the randomization).

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: ADT (Standard of Care)
Description: Androgen Deprivation Therapy (ADT)~The ADT treatment will be chosen at the investigator's discretion, and will be administered according to local standard procedures for up to 2 years.~Patients who may have received ADT prior joining the study should have started the ADT treatment within a maximum of 6 weeks before randomization. Otherwise ADT will be started on Day 1 (or 14 days at the latest after the randomization).

Intervention type: RADIATION
Group type: OTHER
Intervention: radiotherapy
Description: Following randomization, patients will receive dose escalated intensity modulated radiotherapy (IMRT) using normo-fractionation or moderate hypo-fractionation including whole pelvic nodal radiotherapy (WPRT).~Arm A and Arm B:~If Normo-fractionated radiotherapy: Pelvic nodes 46 Gy, seminal vesicles 46-54 Gy and prostate 78 Gy (39 fractions over 8 weeks).~If Hypo-fractionated radiotherapy: Pelvic nodes and seminal vesicles 44 Gy in 20 fractions; prostate 60 Gy delivered concomitantly in 20 fractions over 4 weeks.~Arm C and Arm D:~If Normo-fractionated radiotherapy: Pelvic nodes 46 Gy, seminal vesicles 46 Gy in 23 fractions over 4.5 weeks.~If Hypo-fractionated radiotherapy: Pelvic nodes and seminal vesicles 44 Gy in 20 fractions over 4 weeks.

Intervention type: RADIATION
Group type: EXPERIMENTAL
Intervention: radiotherapy
Description: Following randomization, patients will receive dose escalated intensity modulated radiotherapy (IMRT) using normo-fractionation or moderate hypo-fractionation including whole pelvic nodal radiotherapy (WPRT).~Arm A and Arm B:~If Normo-fractionated radiotherapy: Pelvic nodes 46 Gy, seminal vesicles 46-54 Gy and prostate 78 Gy (39 fractions over 8 weeks).~If Hypo-fractionated radiotherapy: Pelvic nodes and seminal vesicles 44 Gy in 20 fractions; prostate 60 Gy delivered concomitantly in 20 fractions over 4 weeks.~Arm C and Arm D:~If Normo-fractionated radiotherapy: Pelvic nodes 46 Gy, seminal vesicles 46 Gy in 23 fractions over 4.5 weeks.~If Hypo-fractionated radiotherapy: Pelvic nodes and seminal vesicles 44 Gy in 20 fractions over 4 weeks.

Intervention type: RADIATION
Group type: EXPERIMENTAL
Intervention: radiotherapy
Description: Following randomization, patients will receive dose escalated intensity modulated radiotherapy (IMRT) using normo-fractionation or moderate hypo-fractionation including whole pelvic nodal radiotherapy (WPRT).~Arm A and Arm B:~If Normo-fractionated radiotherapy: Pelvic nodes 46 Gy, seminal vesicles 46-54 Gy and prostate 78 Gy (39 fractions over 8 weeks).~If Hypo-fractionated radiotherapy: Pelvic nodes and seminal vesicles 44 Gy in 20 fractions; prostate 60 Gy delivered concomitantly in 20 fractions over 4 weeks.~Arm C and Arm D:~If Normo-fractionated radiotherapy: Pelvic nodes 46 Gy, seminal vesicles 46 Gy in 23 fractions over 4.5 weeks.~If Hypo-fractionated radiotherapy: Pelvic nodes and seminal vesicles 44 Gy in 20 fractions over 4 weeks.

Intervention type: RADIATION
Group type: EXPERIMENTAL
Intervention: radiotherapy
Description: Following randomization, patients will receive dose escalated intensity modulated radiotherapy (IMRT) using normo-fractionation or moderate hypo-fractionation including whole pelvic nodal radiotherapy (WPRT).~Arm A and Arm B:~If Normo-fractionated radiotherapy: Pelvic nodes 46 Gy, seminal vesicles 46-54 Gy and prostate 78 Gy (39 fractions over 8 weeks).~If Hypo-fractionated radiotherapy: Pelvic nodes and seminal vesicles 44 Gy in 20 fractions; prostate 60 Gy delivered concomitantly in 20 fractions over 4 weeks.~Arm C and Arm D:~If Normo-fractionated radiotherapy: Pelvic nodes 46 Gy, seminal vesicles 46 Gy in 23 fractions over 4.5 weeks.~If Hypo-fractionated radiotherapy: Pelvic nodes and seminal vesicles 44 Gy in 20 fractions over 4 weeks.