E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
prostate cancer, eligible for radical prostatectomy and extended pelvic lymph node dissection, with 1-3 pelvic nodal metastases on preoperative PSMA PET |
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E.1.1.1 | Medical condition in easily understood language |
prostate cancer, eligible for radical prostatectomy and extended pelvic lymph node dissection, with 1-3 pelvic nodal metastases on preoperative PSMA PET |
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E.1.1.2 | Therapeutic area | Diseases [C] - Male diseases of the urinary and reproductive systems [C12] |
MedDRA Classification |
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 investigate if surgery is feasible and safe in patients with newly diagnosed lymph node metastatic HSPCa (1-3 metastases; miN1) who have received two cycles of (neo-adjuvant) systemic 177Lutetium (Lu)-labeled prostate-specific membrane antigen (PSMA) radioligand therapy (RLT). |
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E.2.2 | Secondary objectives of the trial |
• To investigate the therapeutic effect of two cycles of 177Lutetium (Lu)-labeled prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) on histopathological variables in the resected prostate gland and lymph-nodes, in patients with newly diagnosed lymph node-positive (1-3 metastases) HSPCa.
• To study the tolerability (toxicity) of study medication.
• To assess the quality of life (QoL) by patient reported outcome measures (PROMS) and specific QoL questionnaires using the EORTC Quality of Life Questionnaire for cancer patients (EORTC-QLQC30 and EORTC-QLQ-PR25) [26,27] and the xerostomia inventory at baseline and at two weeks after each cycle of 177Lu-PSMA RLT.
• To assess the prostate-specific antigen (PSA) free survival at 12 months after two cycles of 177Lu-PSMA RLT and concurrent RARP and ePLND.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Men over 18 years of age - ECOG performance score (PS) 0-1 - Histologically proven adenocarcinoma of the prostate cancer of any grade and/or stage - Any prostate-specific antigen (PSA)-level - Planned to undergo radical prostatectomy (RARP) and extended pelvic lymph node dissection (ePLND) - A pre-operative [68Ga] or [18F] PSMA PET/CT positive for lymphogenic metastatic disease (1-3 metastases; miN1) in the surgical template with a maximum of 6 weeks before study entry - An mpMRI of the abdomen with a maximum of 12 weeks before study entry - Deemed clinically fit for 177Lu-PSMA RLT - eGFR ≥ 30 mL/min/1.73 m2 - Hemoglobin (Hb) ≥ 5.6 mmol/L - Leucocytes ≥ 3.0 x 109/L - Thrombocytes ≥ 100 x 109/l - Provided informed consent
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E.4 | Principal exclusion criteria |
- Previous treatment with any of the following within 6 months of inclusion: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation - Previous PSMA-targeted radioligand therapy - Any systemic anti-cancer therapy (e.g., chemotherapy, immunotherapy or biological therapy [including monoclonal antibodies]) within 28 days prior to day of inclusion - Known hypersensitivity to the components of the study therapy or its analogs - Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy - Patients with signs of M1a-b-c disease on pre-operative PSMA PET/CT - Prior systemic hormonal therapy (ADT)
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary study endpoint is the surgical feasibility and safety of patients with newly diagnosed lymph node metastatic HSPCa who have received two cycles of (neo-adjuvant) systemic 177Lutetium (Lu)-labeled prostate-specific membrane antigen (PSMA) radioligand therapy (RLT). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. the therapeutic effect of 177Lu-PSMA RLT on histopathological variables in the resected prostate gland and the resected pelvic lymph nodes, 2. the assessment of the tolerability (toxicity) of 177Lu-PSMA RLT, 3. the assessment of the quality of life (QoL) and well-being of patients receiving 177Lu-PSMA RLT and 4. the PSA progression-free survival at 12 months after 177Lu-PSMA RLT and radical surgery.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1: t=12 weeks, at surgery 2=3: t=4 and t=10 weeks 4: t=64 weeks after inclusion (12 + 52) |
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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 | No |
E.8.1.1 | Randomised | No |
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 | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |