Ferumoxtran-10-enhanced MRI in Prostate Cancer Patients

Prostate Cancer Clinical Trial

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).

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04261777
• Other study ID #: SPL-01-001
• Status: Recruiting
• Phase: Phase 3
• Start date: May 27, 2020
• Est. completion date: December 2025

Study information

• Verified date: May 2024
• Source: Saving Patients' Lives Medical B.V.
• Contact: Jürgen Feuerstein, Dr.
• Phone: +31 24 303 10 90
• Email: info[@]splmed.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Metastasis
• Prostate Cancer
• Prostatectomy
• Prostatic Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Ghent	Gent
Germany	Charité - Universitätsklinikum Berlin	Berlin
Germany	Vivantes Klinikum Am Urban	Berlin
Germany	Universitätsklinikum Bonn	Bonn
Germany	Universitätsklinikum Köln	Cologne
Germany	Universitätsklinikum Carl Gustav Carus	Dresden
Germany	Universitätsklinikum Düsseldorf	Düsseldorf
Germany	Universitätsklinikum Essen	Essen
Germany	Universitätsklinikum Leipzig	Leipzig
Germany	Universitätsklinikum Schleswig-Holstein Lübeck	Lübeck
Germany	Universitätsmedizin Mannheim Medizinische Fakultät Mannheim der Universität Heidelberg	Mannheim
Netherlands	Nederlands Kanker Instituut Antoni van Leeuwenhoek	Amsterdam
Netherlands	Canisius-Wilhelmina Ziekenhuis Nijmegen	Nijmegen
Netherlands	Radboud University Medical Center	Nijmegen
Switzerland	Inselspital-Universitätsspital Bern	Bern

Sponsors (4)

Lead Sponsor	Collaborator
Saving Patients' Lives Medical B.V.	ABX-CRO advanced pharmaceutical services Forschungsgesellschaft m.b.H., b.e.imaging GmbH, Radboud University Medical Center

Countries where clinical trial is conducted

Belgium,  Germany,  Netherlands,  Switzerland, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Percentage of subjects for whom the patient management plan would be changed based on the Ferrotran®-enhanced MRI.		up to day 105