E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
- Prostate cancer patients with a biochemical recurrence following primary therapy - Hormone-sensitive - Up to 5 metastases on PSMA PET-CT
|
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10071119 |
E.1.2 | Term | Hormone-dependent prostate cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare (radiographic) metastasis-free survival (rPFS) between SBRT plus darolutamide and SBRT only for oligorecurrent PCa. |
|
E.2.2 | Secondary objectives of the trial |
To describe the toxicity of both arms in patients with oligometastatic disease. To determine local control after SBRT + darolutamide in patients with oligometastatic disease. To assess biochemical relapse-free survival (BRFS) in both arms. To assess clinical progression-free survival (PFS) in both arms. To assess time to next systemic therapy in both arms To assess CRPC-free survival in both arms To assess PCa-specific and overall survival in both arms. To assess quality of life in both arms.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Histologically proven initial diagnosis of adenocarcinoma of the prostate Biochemical relapse of PCa following radical local prostate treatment (radical prostatectomy (RP), primary radiotherapy or the combination of RP and prostate bed adjuvant/ salvage radiotherapy) according to the EAU guidelines 2018. Following RP, patients with a biochemical relapse are eligible in case a metastatic relapse is detected even in the absence of prior postoperative prostate bed radiotherapy (adjuvant or salvage). In the absence of prior prostate bed radiotherapy, prostate bed radiotherapy is mandatory for all pT3a or higher or patients with a positive margin at time of RP. For patients without prior RP that have a suspected local recurrence following primary radiotherapy, a biopsy should confirm local recurrence. Patients with a confirmed local recurrence and metastases are eligible in case they also undergo a local salvage therapy. Metastatic relapse on PSMA PET-CT with a maximum of 5 metastases (any M1a, M1b or M1c). Concomitant diagnosis of N1 disease is allowed as long as all lesions are treated with SBRT and the total number of lesions does not exceed 5. PSMA positive lesions will be scored using the MI-RADS scoring system with lesions scored 4 or 5 considered positive19. Asymptomatic for metastatic PCa Age Histologically proven initial diagnosis of adenocarcinoma of the prostate Biochemical relapse of PCa following radical local prostate treatment (radical prostatectomy (RP), primary radiotherapy or the combination of RP and prostate bed adjuvant/ salvage radiotherapy) according to the EAU guidelines 2018. Following RP, patients with a biochemical relapse are eligible in case a metastatic relapse is detected even in the absence of prior postoperative prostate bed radiotherapy (adjuvant or salvage). In the absence of prior prostate bed radiotherapy, prostate bed radiotherapy is mandatory for all pT3a or higher or patients with a positive margin at time of RP. For patients without prior RP that have a suspected local recurrence following primary radiotherapy, a biopsy should confirm local recurrence. Patients with a confirmed local recurrence and metastases are eligible in case they also undergo a local salvage therapy. Metastatic relapse on PSMA PET-CT with a maximum of 5 metastases (any M1a, M1b or M1c). Concomitant diagnosis of N1 disease is allowed as long as all lesions are treated with SBRT and the total number of lesions does not exceed 5. PSMA positive lesions will be scored using the MI-RADS scoring system with lesions scored 4 or 5 considered positive19. Asymptomatic for metastatic PCa Age >=18 years WHO class 0-1 Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial Before patient registration/randomization, written informed consent must be given in accordance with to ICH/GCP, and national/local regulations.18 years WHO class 0-1 Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial Before patient registration/randomization, written informed consent must be given in accordance with to ICH/GCP, and national/local regulations. |
|
E.4 | Principal exclusion criteria |
Local relapse in the prostate gland or prostate bed not suitable for a local salvage treatment Small cell carcinoma of the prostate PSA doubling time >12 months Serum testosterone level <50ng/dl or 1.7 nmol/L at time of randomization Currently receiving ADT or PSA rise while on active treatment with ADT (LHRH-agonist, LHRH-antagonist, anti-androgen or estrogen) within the past 6 weeks Spinal cord compression or impending spinal cord compression Metastases in previously irradiated areas precluding safe delivery of SBRT Contraindications to darolutamide Previous treatment with cytotoxic agent for PCa Treatment during the past month with products known to influence PSA levels (e.g. fluconazole, finasteride, corticosteroids,…) Other active malignancy, except non-melanoma skin cancer or other malignancies with a documented disease-free survival for a minimum of 3 years. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
week 12, week 24 and every 24 weeks until the event of interest has been reached |
|
E.5.2 | Secondary end point(s) |
6.2.1. Clinical progression-free survival 6.2.2. Biochemical relapse-free survival 6.2.3. Time to next systemic therapy 6.2.4. Castrate resistant-free survival 6.2.5. Prostate cancer-specific survival 6.2.6. Overall survival 6.2.7. Acute and late toxicity 6.2.8. Quality of life
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
o Clinical progression-free survival: week 12, week 24 and every 24 weeks until the event of interest has been reached. o Biochemical relapse-free survival: idem o Time to next systemic therapy: idem o Castrate resistant-free survival: idem o Prostate cancer-specific survival: idem o Overall survival: week 12, week 24 and every 24 weeks until the event of interest has been reached Acute and late toxicity: week 12 (acute toxicity), week 24 and every 24 weeks (i.e. late toxicity) until reaching the primary endpoint. Quality of life: At baseline (before randomization) At week 12 , week 24 and every 24 weeks thereafter until time of reaching the primary endpoint.
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Stereotactic body radiotherapy (SBRT) only |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |