Clinical trial NCT04261777: Ferumoxtran-10-enhanced MRI in Prostate Cancer Patients
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).
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Prostate Cancer
Metastasis
Prostatectomy
Keywords: SPL-01-001
ePLND
MRI
USPIO
MR lymphography
Ferrotran
Ultra-small superparamagnetic iron oxide
Nanoparticles
Lead sponsor: Saving Patients' Lives Medical B.V.
Sponsor class: INDUSTRY
Collaborators: name: ABX-CRO advanced pharmaceutical services Forschungsgesellschaft m.b.H.
name: b.e.imaging GmbH
name: Radboud University Medical Center
First posted: 2020-02-10
Enrollment: 172
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

Detailed description: Potential patients for this study will be recruited by up to 15 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.

Eligibility 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

Primary outcomes:
measure: Lymph node metastases will be detected by MRI scan (Ferumoxtran-10-enhanced and unenhanced).
timeFrame: up to day 42
Secondary outcomes:
measure: Number and regions of lymph node metastases present in the follow-up MRI in comparison to pre-surgery MRI (unenhanced and Ferrotran®-enhanced).
timeFrame: up to day 105
measure: Frequency of occurrence and severity of abnormal findings in safety investigations (physical examination, vital signs, 12-lead ECG, clinical laboratory, concomitant medication, adverse events)
timeFrame: day 0 - day 105
measure: Percentage of subjects for whom the patient management plan would be changed based on the Ferrotran®-enhanced MRI.
timeFrame: up to day 105
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Ghent
city: Berlin
country: Germany
facility: Charité - Universitätsklinikum Berlin
city: Berlin
country: Germany
facility: Vivantes Klinikum Am Urban
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Cologne
country: Germany
facility: Universitätsklinikum Köln
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein Lübeck
city: Mannheim
country: Germany
facility: Universitätsmedizin Mannheim Medizinische Fakultät Mannheim der Universität Heidelberg
city: Amsterdam
country: Netherlands
facility: Nederlands Kanker Instituut Antoni van Leeuwenhoek
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
city: Nijmegen
country: Netherlands
facility: Canisius-Wilhelmina Ziekenhuis Nijmegen
city: Bern
country: Switzerland
facility: Inselspital-Universitätsspital Bern
Study officials:
References:
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.
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.
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.
citation: 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.