Ferumoxtran-10-enhanced MRI in Prostate Cancer Patients

A Confirmatory, Prospective, Open-label, Single-arm, Reader-blinded Multi-centre Phase 3 Study to Assess the Diagnostic Accuracy of Ferumoxtran-10-enhanced Magnetic Resonance Imaging (MRI) and Unenhanced MRI in Reference to Histopathology in Newly-diagnosed Prostate Cancer (PCA) Patients, Scheduled for Radical Prostatectomy (RP) With Extended Pelvic Lymph Node Dissection (ePLND).

This will be a confirmatory, prospective, open-label, single-arm, reader-blinded, multi-centre phase 3 study to assess the diagnostic accuracy and safety of Ferrotran®-enhanced MRI in comparison to unenhanced MRI in the detection of pelvic lymph node metastases in newly-diagnosed adult patients with prostate cancer and an intermediate to high risk for lymph node metastases, based on the D'Amico criteria.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer; Metastasis; Prostatectomy
• Intervention / Treatment: Drug: Ferrotran® (Ferumoxtran-10)

Detailed Description

Potential patients for this study will be recruited by up to 10 centres specialised in prostate cancer. Study sites will be interdisciplinary, consisting of a uro-oncology sub-site, and a radiology sub-site with high-quality MRI, surgery and pathology. Study visits will be typically conducted at the recruiting sub-site, or as institutionally appropriate. Treatment visits for patients will be performed in the collaborating sub-site. Patients will be invited for study participation by the investigators in the context of specialised clinics. Interested patients will be provided with an information sheet and will undergo a detailed informed consent procedure prior to any study procedures. Recruitment will be continued until a sufficient number of patients have undergone Ferrotran® imaging and histopathological evaluation.

To compensate for an expected drop-out rate of 15% to 20%, recruitment will only be stopped as soon as at least 69 evaluable positive (patients positive) and at least 104 evaluable negative (patients negative) patients are available for analysis.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jürgen Feuerstein, Dr.; Phone Number: +31 24 303 10 90; Email: info@splmed.com
• Study Contact Backup: Name: Volker Meyer, Dr.; Phone Number: +49 351 21 444 0; Email: info@abx-cro.com

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • Recruiting
    • Universitair Ziekenhuis Ghent
• Germany
  • Berlin, Germany, 10967
    • Recruiting
    • Vivantes Klinikum Am Urban
  • Berlin, Germany, 10117
    • Recruiting
    • Charité - Universitätsklinikum Berlin
  • Bonn, Germany, 53127
    • Recruiting
    • Universitätsklinikum Bonn
  • Cologne, Germany, 50937
    • Recruiting
    • Universitätsklinikum Köln
  • Dresden, Germany, 01307
    • Recruiting
    • Universitätsklinikum Carl Gustav Carus
  • Düsseldorf, Germany, 40225
    • Recruiting
    • Universitätsklinikum Düsseldorf
  • Essen, Germany, 45147
    • Recruiting
    • Universitätsklinikum Essen
  • Leipzig, Germany, 04103
    • Recruiting
    • Universitätsklinikum Leipzig
  • Lübeck, Germany, 23538
    • Recruiting
    • Universitätsklinikum Schleswig-Holstein Lübeck
  • Mannheim, Germany, 68167
    • Not yet recruiting
    • Universitätsmedizin Mannheim Medizinische Fakultät Mannheim der Universität Heidelberg
• Netherlands
  • Amsterdam, Netherlands, 1006
    • Recruiting
    • Nederlands Kanker Instituut Antoni van Leeuwenhoek
  • Nijmegen, Netherlands, 6525
    • Recruiting
    • Radboud University Medical Center
  • Nijmegen, Netherlands, 6532
    • Recruiting
    • Canisius-Wilhelmina Ziekenhuis Nijmegen
• Switzerland
  • Bern, Switzerland, 3010
    • Recruiting
    • Inselspital-Universitatsspital Bern

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

   1. PSA ≥10 ng/mL or
   2. Gleason-Score ≥7 or
   3. 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.

Exclusion Criteria:

1. Any contraindication to MRI, as per standard criteria.
2. Any radiation therapy 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: SPL-01-001

Drug: Ferrotran® (Ferumoxtran-10); Ferrotran® in a dose of 0.13 mL/kg body weight of the reconstituted freeze-dried preparation (i.e. 2.6 mgFe/kg body weight). The recommended dose should be diluted in 100 mL of NaCl 9 mg/mL (0.9%) solution for injection/infusion prior to administration via the infusion filter as a slow intravenous infusion over 30 minutes (at a maximum rate of 4 mL/min). Ferrotran® will be administered once to each patient. Histologically confirmed diagnosis and pre-operative staging are performed prior to the study as part of standard care. Surgery (RP with ePLND) and sampling of tissue specimens is performed after the Ferrotran®-enhanced MRI as part of standard care.; Other Names: Ferrotran Lyophilisate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lymph node metastases will be detected by MRI scan (Ferumoxtran-10-enhanced and unenhanced).	True positive fraction and false positive fraction of identified tumour tissue in pelvic lymph nodes will be analysed by histopathology as established reference method.	up to day 42

Secondary Outcome Measures

Outcome Measure	Time Frame
Number and regions of lymph node metastases present in the follow-up MRI in comparison to pre-surgery MRI (unenhanced and Ferrotran®-enhanced).	up to day 105
Frequency of occurrence and severity of abnormal findings in safety investigations (physical examination, vital signs, 12-lead ECG, clinical laboratory, concomitant medication, adverse events)	day 0 - day 105
Percentage of subjects for whom the patient management plan would be changed based on the Ferrotran®-enhanced MRI.	up to day 105

Collaborators and Investigators

• Sponsor: Saving Patients' Lives Medical B.V.
• Collaborators: Radboud University Medical Center; ABX-CRO advanced pharmaceutical services Forschungsgesellschaft m.b.H.; b.e.imaging GmbH
• Investigators: Study Chair: Jelle Barentsz, MD, Radboud University Medical Center

Publications and helpful links

General Publications

• D'Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, Tomaszewski JE, Renshaw AA, Kaplan I, Beard CJ, Wein A. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 1998 Sep 16;280(11):969-74. doi: 10.1001/jama.280.11.969.
• Harisinghani MG, Barentsz J, Hahn PF, Deserno WM, Tabatabaei S, van de Kaa CH, de la Rosette J, Weissleder R. Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med. 2003 Jun 19;348(25):2491-9. doi: 10.1056/NEJMoa022749. Erratum In: N Engl J Med. 2003 Sep 4;349(10):1010.
• Heesakkers RA, Hovels AM, Jager GJ, van den Bosch HC, Witjes JA, Raat HP, Severens JL, Adang EM, van der Kaa CH, Futterer JJ, Barentsz J. MRI with a lymph-node-specific contrast agent as an alternative to CT scan and lymph-node dissection in patients with prostate cancer: a prospective multicohort study. Lancet Oncol. 2008 Sep;9(9):850-6. doi: 10.1016/S1470-2045(08)70203-1. Epub 2008 Aug 15.
• Heesakkers RA, Jager GJ, Hovels AM, de Hoop B, van den Bosch HC, Raat F, Witjes JA, Mulders PF, van der Kaa CH, Barentsz JO. Prostate cancer: detection of lymph node metastases outside the routine surgical area with ferumoxtran-10-enhanced MR imaging. Radiology. 2009 May;251(2):408-14. doi: 10.1148/radiol.2512071018.

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2020
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): March 1, 2024

Study Registration Dates

• First Submitted: January 27, 2020
• First Submitted That Met QC Criteria: February 5, 2020
• First Posted (Actual): February 10, 2020

Study Record Updates

• Last Update Posted (Actual): May 8, 2023
• Last Update Submitted That Met QC Criteria: May 5, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: MRI; USPIO; MR lymphography; Nanoparticles; SPL-01-001; ePLND; Ferrotran; Ultra-small superparamagnetic iron oxide
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: SPL-01-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No