The aim is to investigate whether the addition of short-term androgen deprivation therapy (ADT) during 1 month or short-term ADT during 6 months together with an androgen receptor targeted therapy (ARTA) to metastasis-directed therapy (MDT) significantly prolongs poly-metastatic free survival (PMFS) and/or metastatic castration-refractory prostate cancer free survival (mCRPC-FS) in patients with oligorecurrent hormone sensitive prostate cancer.
Histologically proven initial diagnosis of prostate adenocarcinoma
Priory treated and controlled primary tumor
Biochemical recurrence defined by prostate-specific antigen (PSA) values >0,2 ng/ml (i.e., two consecutive increases) following radical prostatectomy + postoperative radiotherapy and a PSA value of 2 ng/ml above the nadir after high-dose RT.
Oligorecurrent disease defined as a maximum of 5 extracranial metastases in any organ, diagnosed on PSMA PET-CT or PSMA PET-MRI reported according to the E-PSMA consensus guidelines for interpretation of PSMA-PET (26). Nodal (N1) disease can be included only when accompanied by M1a-c disease, provided that the total number of spots does not exceed 5.
Any disorder, which in the Investigator's opinion might jeopardise the participant's safety or compliance with the protocol
Any prior or concomitant treatment(s) that might jeopardise the participant's safety or that would compromise the integrity of the Trial
Participation in an interventional Trial with an investigational medicinal product (IMP) or device
Serum testosterone level at castration level.
Parallel
Radiotherapy (SBRT) and/or surgery (metastasectomy)
Other interventionMetastasis-directed therapay (surgery and/or radiotherapy) as treatment for oligorecurrent lesions
Androgen deprivation therapy
DrugArm B: gosereline 3.6 mg sc, leuproreline 7.5 mg sc, triptoreline 3.75 mg im Arm C: gosereline 3.6 mg sc 1x/month or gosereline 10.8 mg sc or leuproreline 7.5 mg sc 1x/month or leuproreline 45 mg sc or triptoreline 3.75 mg im 1x/month or triptoreline 11.5 mg im 1x/3months or triptoreline 22.5 mg im
Androgen receptor targeted therapy
DrugEnzalutamide
Poly-metastatic free survival (PMFS)
from the last day of MDT until the first day of poly-progression which is defined as the detection \> 5 new lesions at PSMA PET-CT or PSMA PET-MRI (+/- combined with MRI if needed to improve diagnostic accuracy). In case of poly-progression, pADT will be considered the standard-of-care. Other indications to start pADT are local progression of an irradiated site and/or or clinical symptoms caused by local progression. In all cases, the initiation of pADT will only be carried out after approval of the multidisciplinary tumor board. Any decision to start with pADT will be reported with date and specific reason. If recurrence occurs in 5 lesions or less a new MDT is proposed if technically feasible.
Metastatic castration-refractory prostate cancer free survival (mCRPC-FS)
mCRPC-FS will be calculated from the last day of MDT until the first day of diagnosis of castration-resistant prostate cancer (CRPC). CRPC is defined according to the contemporary EAU-guidelines as the time to biochemical and/or clinical progression at castrate testosterone levels (\< 50 ng/dl). Biochemical progression is defined as three consecutive PSA rises (1 week interval), of which at least 2 rises with a PSA level of \> 2 ng/ml and a rise of 50% above the nadir PSA level
Biochemical progression-free survival (bPFS)
bPFS will be calculated from the last day of MDT until the first day of biochemical relapse (BcR). BcR is defined as three consecutive PSA rises (1 week interval), of which at least 2 rises with a PSA level of \> 2 ng/ml and a rise of 50% above the nadir PSA level.
Clinical progression free survival (cPFS)
cPFS will be calculated from the last day of MDT until the first day of progression (local, nodal or metastatic) on PSMA PET-CT or PSMA PET-MRI. Imaging is performed in case of BcR, defined as above. Progression on PSMA PET-CT or PSMA PET-MRI will be defined as in the consensus statements on PSMA PET-CT or PSMA PET-MRI response assessment criteria in prostate cancer: * the appearance of 2 or more new PSMA PET-CT or PSMA PET-MRI lesions or increase of uptake or tumor PET volume of at least 30%. * OR the appearance of 1 new lesion with a high suspicion on PSMA PET-CT or PSMA PET-MRI
Cancer Specific Survival (CSS)
Cancer specific survival (CSS) will be calculated from last day of treatment until PCa death.
Click on the lead sponsor to view all of their trials.
