E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
newly-diagnosed prostate cancer (PCA) |
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E.1.1.1 | Medical condition in easily understood language |
newly-diagnosed prostate cancer (PCA) |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Investigative Techniques [E05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060862 |
E.1.2 | Term | Prostate cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
1. To confirm superiority of Ferrotran®-enhanced MRI over unenhanced MRI in sensitivity to detect metastases in normal size pelvic lymph nodes in using histopathology after lymph node dissection as established reference method (Gold Standard). 2. To confirm non-inferiority of Ferrotran®-enhanced MRI compared with unenhanced MRI in specificity with a margin of 15% in using histopathology after lymph node dissection as established reference method (Gold Standard).
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E.2.2 | Secondary objectives of the trial |
1. To confirm non-inferiority of Ferrotran-enhanced MRI compared with unenhanced MRI in sensitivity with a margin of 15% to detect any pelvic lymph node metastases in using histopathology after lymph node dissection as established reference method 2. To determine positive predictive value, negative predictive value, and accuracy for Ferrotran-enhanced MRI and for unenhanced MRI in detecting normal size pelvic lymph node metastases 3. To determine positive predictive value, negative predictive value, and accuracy for Ferrotran-enhanced MRI and for unenhanced MRI in detecting any pelvic lymph node metastases 4. To evaluate the number and sites (gross- and sub-regions) of affected lymph nodes removed and not removed by ePLND comparing the unenhanced MRI at follow-up and the pre-surgery MRIs 5. To assess the clinical safety and tolerability of a single slow drip Ferrotran infusion [...] see protocol for all secondary objectives
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Voluntarily given and written informed consent. 2) Male ≥18 years of age. 3) Histologically newly-confirmed adenocarcinoma of the prostate. 4) Medium to high risk for lymph node metastasis, defined by either: a. PSA ≥10 ng/mL or b. Gleason-Score ≥7 or c. Stage cT2b or cT2c or T3 or T4 5) Patients scheduled for radical prostatectomy (RP) with extended lymph node dissection (ePLND) between Day 7 and Day 42 after Ferrotran®-enhanced MRI. 6) Consent to practice contraception until end of study, including female partners of childbearing potential. Effective contraceptive measures include hormonal oral, injected or implanted female contraceptives, male condom, vaginal diaphragm, cervical cap, intrauterine device.
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E.4 | Principal exclusion criteria |
1) Any contraindication to MRI, as per standard criteria. 2) Any radiation therapy or or systemic antiproliferative (chemo-, immuno, or hormonal) therapy for prostate cancer (Lupron, Taxotere, Casodex, Eulexin, Zoladex, etc.) prior to screening and until after post-surgery FUP MRI. 3) Known hypersensitivity to Ferrotran® or its components such as dextran 4) Known hypersensitivity to other parenteral iron products. 5) Acute allergy, including drug allergies and allergic asthma. 6) Evidence of iron overload or disturbances in the utilisation of iron (e.g., haemochromatosis, haemosiderosis, chronic haemolytic anaemia with frequent blood transfusions). 7) Presence of liver dysfunction. 8) Any other investigational medicinal product within 30 days prior to receiving study medication until end of study visit. 9) Simultaneous participation in any other clinical trial. 10) Abnormal safety laboratory values at screening or baseline that are assessed by the principal investigator as clinically relevant. 11) Patients not able to declare meaningful informed consent on their own (e.g. with legal guardian for mental disorders), or other vulnerable patients (e.g. under arrest). 12) Patients with acute SARS-CoV-2 infection
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E.5 End points |
E.5.1 | Primary end point(s) |
The co-primary endpoints for this study will observed sensitivity and observed specificity of the Ferrotran®-enhanced MRI compared with the unenhanced baseline MRI, in assessing the nodal status (metastatic / non-metastatic) of the patient with respect to the lymph nodes considered for lymphadenectomy. Specificity and sensitivity of Ferrotran®-enhanced and un-enhanced MRI will be obtained by comparison of each method to histopathology results, and not by direct comparison of the MRI methods with each other. The patient will be considered metastatic (patientpositive) if at least one lymph node is diagnosed as metastatic is confirmed in histopathology.
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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) |
Secondary endpoints:
- Secondary efficacy endpoints: a) The number and regions of lymph node metastases present in the follow-up MRI in comparison to pre-surgery MRI (unenhanced and Ferrotran®-enhanced). b) Patients with additional dissection of lymph nodes outside the defined 8 pelvic regions due to Ferrotran® uptake i.e. pre-sacral, peri-rectal, para-aortic, which are not the standard of ePLND. The secondary efficacy endpoints will be assessed on the basis of the secondary efficacy variables as described below.
- Endpoint for patient management: Impact of Ferrotran®-enhanced MRI on patient management Endpoint for inter reader and intra reader variability Inter reader and intra reader variability will be obtained by comparing readers results on primary reads and re-reads.
- Endpoints for safety and tolerability: Frequency of occurrence and severity of abnormal findings in safety investigations (physical examination, vital signs, 12 lead ECG, clinical laboratory, AEs, concomitant medication) after a single slow drip Ferrotran® infusion. The assessment of safety and tolerability endpoints will be based on secondary safety and tolerability variables as described below.
- Exploratory endpoints: Qualitative assessment of • Vessel visibility • Image quality
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary efficacy endpoints: Day 1 & surgery Endpoint for patient management: Day 1 until surgery Endpoints for safety and tolerability: Day 1 until Day 7, Safety Follow Up & End of Study Exploratory endpoints: Day 1 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
single-arm, reader-blinded |
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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
| 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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Switzerland |
Belgium |
Germany |
Netherlands |
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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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The end of the trial is defined as the last visit of the last patient or the last date of follow-up of toxicities, if required (whichever is the later). |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |