E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Oligo-metastatic adenocarcinoma of the prostate. |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
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 |
The main objective of this study is to assess the difference in the fraction of patients with low volume, hormone sensitive metastatic PCa that meet EOT 1 criteria after 177Lu-PSMA RLT compared to those that have a deferred androgen deprivation treatment schedule. EOT 1 is defined by: - Clinical progression determined by the treating physician (e.g. increasing pain from metastases) - A 100% increase in PSA after cycle one blood draw (BASELINE) during study. Exception: PSA increase in the first 12 weeks after the first treatment injection as was defined by the PCWG3 criteria. |
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E.2.2 | Secondary objectives of the trial |
- To assess ADT free survival in patients receiving 177Lu-PSMA RLT. ADT free survival is defined by the date ADT is started or death related to PCa. - To evaluate the clinical efficacy of multiple doses 177Lu-PSMA radioligand therapy in patients with low volume, hormone sensitive metastatic PCa. - To assess progression free survival, defined as from the time frominclusion to date of evidence of: clinical progression, death from any cause, PSA progression, or radiographic progression, whichever occurs first. - To evaluate the tolerability and toxicity of 177Lu-PSMA RLT defined by NCI Common Terminology Criteria for Adverse Events v5.0. - To evaluate the quality of life before and up to 6 months after 177Lu- PSMA RLT using the following questionnaires: EORTC QLQ-C30, QLQPR25 & xerostomia inventory. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histological proven adenocarcinoma of the prostate with archived tumor material. - Biochemical recurrence or clinical progression (PSA > 1.0 μg/l). - ECOG 0-1. - PSA-doubling time < 6 months. - 18F-PSMA-PET-CT positive metastases in bones and/or lymph nodes (N1/M1ab): ≥1, maximally 5 metastases . - Local treatment for oligometastases with radiotherapy or surgery appears to be no option anymore (due to prior treatment or the location of the metastatic lesions). - No prior hormonal therapy (including any androgen directed treatment such as Bicalutamide, Apalutamide, Abiraterone or Enzalutamide) or taxane based chemotherapy (docetaxel or cabazitaxel); testosterone > 1.7 nmol/l. Exception: local prostate cancer treated with local radiotherapy plus adjuvant ADT; these patients need to be stopped with ADT at least 6 months. - No visceral metastases. - Laboratory values: • White blood cells > 3.0 x 109/l • Platelet count > 75 x 109/l • Hemoglobin > 6.2 mmol/l • ASAT, ALAT < 3 x ULN • MDRD-GFR ≥ 50 ml/min - Signed informed consent. |
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E.4 | Principal exclusion criteria |
- A detectable lesion on the 18F-PSMA PET/CT with significant PSMA avidity, defined by a SUVmax > 10 (partial volume corrected). - A known subtype other than prostate adenocarcinoma. - Previous PSMA based radioligand treatment. - Visceral or brain metastases. - Any medical condition present that in the opinion of the investigator will affect patients' clinical status when participating in this trial. - Prior hip replacement surgery potentially influencing performance of PSMA PET/CT. - Sjogren's syndrome. - A second active malignancy other than prostate cancer. - Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To assess the difference in the fraction of patients that have disease progression during the 6 month follow up of this study after 177Lu-PSMA RLT or a deferred androgen deprivation treatment schedule. |
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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) |
- ADT-free survival. - PSA response. - Toxicity based on NCI CTCAE v5.0 criteria. - Radiological state of the disease, expressed in the difference in amount and size of suspicious nodes on 18F-PSMA PET/CT and (whole body) MRI between pre- and post-therapy. - Quality of Life assessments. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
During study and up to End-of-Study (Week 24). |
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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 | 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 |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |