Study: NCT06320067

Intervention type: OTHER
Group type: EXPERIMENTAL
Intervention: 177Lu-PSMA-617
Description: 177Lu-PSMA-617 is a nuclear medicine therapy. Patients will receive 177Lu-PSMA-617 to a dose of 7.4GBq. Each cycle will consist of 2 doses, 1 week apart (on day 1 and day 8) and will last 6 weeks. Treatment will be given for up to 3 cycles (6 doses).

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Niraparib and Abiraterone Acetate Dual Action Tablet DAT
Description: Combination product containing Niraparib (PARP inhibitor) and Abiraterone Acetate (ARSI). The regular-strength dual-action tablet (DAT) contains 100 mg niraparib/500mg AA per tablet. Patients take 2 tablets a day and receive a of total dose 200 mg niraparib/1000 mg AA. A low-strength DAT tablet containing 50 mg niraparib/500 mg AA may be available for participants requiring a dose reduction of niraparib.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Abiraterone Acetate
Description: Abiraterone Acetate is an ARSI. Single agent Abiraterone Acetate may be used in patients randomised to receive Niraparib and Abiraterone Acetate.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Apalutamide
Description: Apalutamide is an ARSI administered as a 240mg oral dose (four tablets taken together at the same time every day) with or without food. It is given daily in 28-day cycles.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Androgen Deprivation Therapy (ADT)
Description: Long-term, continuous treatment with ADT (bilateral orchidectomy, LHRH agonists or LHRH antagonists) if not previously surgically castrated. The choice of ADT is at the discretion of the investigator. This will be given as standard of care as per local guidelines.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Androgen Deprivation Therapy (ADT)
Description: Long-term, continuous treatment with ADT (bilateral orchidectomy, LHRH agonists or LHRH antagonists) if not previously surgically castrated. The choice of ADT is at the discretion of the investigator. This will be given as standard of care as per local guidelines.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Androgen Deprivation Therapy (ADT)
Description: Long-term, continuous treatment with ADT (bilateral orchidectomy, LHRH agonists or LHRH antagonists) if not previously surgically castrated. The choice of ADT is at the discretion of the investigator. This will be given as standard of care as per local guidelines.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Androgen Deprivation Therapy (ADT)
Description: Long-term, continuous treatment with ADT (bilateral orchidectomy, LHRH agonists or LHRH antagonists) if not previously surgically castrated. The choice of ADT is at the discretion of the investigator. This will be given as standard of care as per local guidelines.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Androgen Deprivation Therapy (ADT)
Description: Long-term, continuous treatment with ADT (bilateral orchidectomy, LHRH agonists or LHRH antagonists) if not previously surgically castrated. The choice of ADT is at the discretion of the investigator. This will be given as standard of care as per local guidelines.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Androgen Deprivation Therapy (ADT)
Description: Long-term, continuous treatment with ADT (bilateral orchidectomy, LHRH agonists or LHRH antagonists) if not previously surgically castrated. The choice of ADT is at the discretion of the investigator. This will be given as standard of care as per local guidelines.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Androgen Receptor Signalling Inhibitor (ARSI)
Description: Second generation ARSI (Abiraterone Acetate and Prednisolone \[AA+P\], Enzalutamide, Apalutamide or Darolutamide). This will be given as standard of care as per local guidelines.~Abiraterone acetate will be administered as a single 1000mg once daily dose (4 tablets to be taken together once a day) with prednisolone 5mg once daily to prevent secondary mineralocorticoid excess.~Enzalutamide will be administered as a 160mg oral dose (four capsules taken together at the same time every day) with or without food. Enzalutamide is administered daily in 28-day cycles.~Apalutamide will be administered as 240mg oral dose (four tablets taken together at the same time every day) with or without food. Apalutamide is administered daily in 28-day cycles. Patients require thyroid function monitoring.~Darolutamide will be administered as 600mg oral dose (two 300mg tablets taken together) with or without food. Darolutamide is administered twice daily in 28-day cycles.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Androgen Receptor Signalling Inhibitor (ARSI)
Description: Second generation ARSI (Abiraterone Acetate and Prednisolone \[AA+P\], Enzalutamide, Apalutamide or Darolutamide). This will be given as standard of care as per local guidelines.~Abiraterone acetate will be administered as a single 1000mg once daily dose (4 tablets to be taken together once a day) with prednisolone 5mg once daily to prevent secondary mineralocorticoid excess.~Enzalutamide will be administered as a 160mg oral dose (four capsules taken together at the same time every day) with or without food. Enzalutamide is administered daily in 28-day cycles.~Apalutamide will be administered as 240mg oral dose (four tablets taken together at the same time every day) with or without food. Apalutamide is administered daily in 28-day cycles. Patients require thyroid function monitoring.~Darolutamide will be administered as 600mg oral dose (two 300mg tablets taken together) with or without food. Darolutamide is administered twice daily in 28-day cycles.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Androgen Receptor Signalling Inhibitor (ARSI)
Description: Second generation ARSI (Abiraterone Acetate and Prednisolone \[AA+P\], Enzalutamide, Apalutamide or Darolutamide). This will be given as standard of care as per local guidelines.~Abiraterone acetate will be administered as a single 1000mg once daily dose (4 tablets to be taken together once a day) with prednisolone 5mg once daily to prevent secondary mineralocorticoid excess.~Enzalutamide will be administered as a 160mg oral dose (four capsules taken together at the same time every day) with or without food. Enzalutamide is administered daily in 28-day cycles.~Apalutamide will be administered as 240mg oral dose (four tablets taken together at the same time every day) with or without food. Apalutamide is administered daily in 28-day cycles. Patients require thyroid function monitoring.~Darolutamide will be administered as 600mg oral dose (two 300mg tablets taken together) with or without food. Darolutamide is administered twice daily in 28-day cycles.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Androgen Receptor Signalling Inhibitor (ARSI)
Description: Second generation ARSI (Abiraterone Acetate and Prednisolone \[AA+P\], Enzalutamide, Apalutamide or Darolutamide). This will be given as standard of care as per local guidelines.~Abiraterone acetate will be administered as a single 1000mg once daily dose (4 tablets to be taken together once a day) with prednisolone 5mg once daily to prevent secondary mineralocorticoid excess.~Enzalutamide will be administered as a 160mg oral dose (four capsules taken together at the same time every day) with or without food. Enzalutamide is administered daily in 28-day cycles.~Apalutamide will be administered as 240mg oral dose (four tablets taken together at the same time every day) with or without food. Apalutamide is administered daily in 28-day cycles. Patients require thyroid function monitoring.~Darolutamide will be administered as 600mg oral dose (two 300mg tablets taken together) with or without food. Darolutamide is administered twice daily in 28-day cycles.

Intervention type: RADIATION
Group type: ACTIVE_COMPARATOR
Intervention: Local Radiotherapy
Description: Either 36.25Gy given in 5 fractions over 1-2 weeks to prostate or 60Gy in 20 fractions over 4 weeks to prostate (± 47Gy in 20 fractions to pelvic lymph nodes ± 51Gy in 20 fractions boost to involved nodes).

Intervention type: RADIATION
Group type: ACTIVE_COMPARATOR
Intervention: Local Radiotherapy
Description: Either 36.25Gy given in 5 fractions over 1-2 weeks to prostate or 60Gy in 20 fractions over 4 weeks to prostate (± 47Gy in 20 fractions to pelvic lymph nodes ± 51Gy in 20 fractions boost to involved nodes).

Intervention type: RADIATION
Group type: ACTIVE_COMPARATOR
Intervention: Local Radiotherapy
Description: Either 36.25Gy given in 5 fractions over 1-2 weeks to prostate or 60Gy in 20 fractions over 4 weeks to prostate (± 47Gy in 20 fractions to pelvic lymph nodes ± 51Gy in 20 fractions boost to involved nodes).

Intervention type: RADIATION
Group type: EXPERIMENTAL
Intervention: Local Radiotherapy
Description: Either 36.25Gy given in 5 fractions over 1-2 weeks to prostate or 60Gy in 20 fractions over 4 weeks to prostate (± 47Gy in 20 fractions to pelvic lymph nodes ± 51Gy in 20 fractions boost to involved nodes).

Intervention type: RADIATION
Group type: EXPERIMENTAL
Intervention: Local Radiotherapy
Description: Either 36.25Gy given in 5 fractions over 1-2 weeks to prostate or 60Gy in 20 fractions over 4 weeks to prostate (± 47Gy in 20 fractions to pelvic lymph nodes ± 51Gy in 20 fractions boost to involved nodes).

Intervention type: RADIATION
Group type: EXPERIMENTAL
Intervention: Local Radiotherapy
Description: Either 36.25Gy given in 5 fractions over 1-2 weeks to prostate or 60Gy in 20 fractions over 4 weeks to prostate (± 47Gy in 20 fractions to pelvic lymph nodes ± 51Gy in 20 fractions boost to involved nodes).

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Prednisolone
Description: Prednisolone should also be administered 5mg daily using local pharmacy prescribing.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Docetaxel
Description: Maximum of 6 cycles every 3 weeks may be given at a dose of 75mg/m2 by IV infusion.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Docetaxel
Description: Maximum of 6 cycles every 3 weeks may be given at a dose of 75mg/m2 by IV infusion.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Docetaxel
Description: Maximum of 6 cycles every 3 weeks may be given at a dose of 75mg/m2 by IV infusion.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Docetaxel
Description: Maximum of 6 cycles every 3 weeks may be given at a dose of 75mg/m2 by IV infusion.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Docetaxel
Description: Maximum of 6 cycles every 3 weeks may be given at a dose of 75mg/m2 by IV infusion.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Docetaxel
Description: Maximum of 6 cycles every 3 weeks may be given at a dose of 75mg/m2 by IV infusion.