Ferumoxtran-10-enhanced MRI in Prostate Cancer Patients

• ClinicalTrials.gov Identifier: NCT04261777
• Recruitment Status: Recruiting
• First Posted: February 10, 2020
• Last Update Posted: May 8, 2023
• Sponsor: Saving Patients' Lives Medical B.V.
• Collaborators: ABX-CRO advanced pharmaceutical services Forschungsgesellschaft m.b.H.; b.e.imaging GmbH; Radboud University Medical Center
• Information provided by (Responsible Party): Saving Patients' Lives Medical B.V.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer; Metastasis; Prostatectomy	Drug: Ferrotran® (Ferumoxtran-10)	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 200 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: 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).
• Actual Study Start Date: May 27, 2020
• Estimated Primary Completion Date: December 2023
• Estimated Study Completion Date: March 2024

Arms and Interventions

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 Name: Ferrotran Lyophilisate

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: male with prostate cancer
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Jürgen Feuerstein, Dr.; +31 24 303 10 90; info@splmed.com

Contact: Volker Meyer, Dr.; +49 351 21 444 0; info@abx-cro.com

Locations

Belgium

Universitair Ziekenhuis Ghent; Recruiting

Gent, Belgium, 9000

Germany

Charité - Universitätsklinikum Berlin; Recruiting

Berlin, Germany, 10117

Vivantes Klinikum Am Urban; Recruiting

Berlin, Germany, 10967

Universitätsklinikum Bonn; Recruiting

Bonn, Germany, 53127

Universitätsklinikum Köln; Recruiting

Cologne, Germany, 50937

Universitätsklinikum Carl Gustav Carus; Recruiting

Dresden, Germany, 01307

Universitätsklinikum Düsseldorf; Recruiting

Düsseldorf, Germany, 40225

Universitätsklinikum Essen; Recruiting

Essen, Germany, 45147

Universitätsklinikum Leipzig; Recruiting

Leipzig, Germany, 04103

Universitätsklinikum Schleswig-Holstein Lübeck; Recruiting

Lübeck, Germany, 23538

Universitätsmedizin Mannheim Medizinische Fakultät Mannheim der Universität Heidelberg; Not yet recruiting

Mannheim, Germany, 68167

Netherlands

Nederlands Kanker Instituut Antoni van Leeuwenhoek; Recruiting

Amsterdam, Netherlands, 1006

Radboud University Medical Center; Recruiting

Nijmegen, Netherlands, 6525

Canisius-Wilhelmina Ziekenhuis Nijmegen; Recruiting

Nijmegen, Netherlands, 6532

Switzerland

Inselspital-Universitätsspital Bern; Recruiting

Bern, Switzerland, 3010

Sponsors and Collaborators

Saving Patients' Lives Medical B.V.

ABX-CRO advanced pharmaceutical services Forschungsgesellschaft m.b.H.

b.e.imaging GmbH

Radboud University Medical Center

More Information

Publications:

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.

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.

• Responsible Party: Saving Patients' Lives Medical B.V.
• ClinicalTrials.gov Identifier: NCT04261777
• Other Study ID Numbers: SPL-01-001
• First Posted: February 10, 2020
• Last Update Posted: May 8, 2023
• Last Verified: April 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Saving Patients' Lives Medical B.V.:

SPL-01-001; ePLND; MRI; USPIO; MR lymphography; Ferrotran; Ultra-small superparamagnetic iron oxide; Nanoparticles

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases