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).
Organizational Data
- DRKS-ID:
- DRKS00019106
- Recruitment Status:
- Recruiting ongoing
- Date of registration in DRKS:
- 2020-02-26
- Last update in DRKS:
- 2024-04-26
- Registration type:
- Prospective
Acronym/abbreviation of the study
SPL-01-001
URL of the study
https://ferrotran.com/?lang=de
Brief summary in lay language
The aim of this study is to assess if Ferumoxtran-10 is suitable contrast agent for magnetic resonance imaging (MRI) to identify small lymph nodes metastasis in the pelvic region. This study is conducted to evaluate the diagnostic accuracy and safety of Ferumoxtran-10. The study is intended for patients suffering from prostate cancer with an intermediate to high risk for metastasis and which are scheduled for a prostatcetomy with extended lymph node removal. Ferumoxtran-10 consists of ultra small iron-particles and is sensitive and specific for the detection of lymph node metastases. A solution of Ferumoxtran-10 is administered via injection into the vein and will be taken up in healthy tissue but not in cancer tissue. In the imaging process the Ferumoxtran-10 particles which are distributed to the whole body can be made visible. Healthy tissue appears darkened because the Ferumoxtran-10 was takes up whereas the cancer tissue stayes lighter. This method allows the detection of very small lymph nodes (2 mm) in comparison to normally used scans which can identify metastases from a size of 7-8 mm.
Brief summary in scientific language
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 patients with prostate cancer and an intermediate to high risk for lymph node metastases, based on the D'Amico criteria.
Health condition or problem studied
- ICD10:
- C61 - Malignant neoplasm of prostate
- Free text:
- metastasised lymph nodes in the pelvic region
- Free text:
- high risk prostate cancer
- Healthy volunteers:
- No
Interventions, Observational Groups
- Arm 1:
- After signing the consent form, inclusion and exclusion criteria are checked and screening examinations (e.g. blood pressure, pulse, 12-channel electrocardiogram (ECG) and normal MRI) are performed. On the day of treatment (day 0), a physical examination, vital signs an weight again assessed before administration of Ferumoxtran-10 (0.13 mL/kg). The contrast medium is administered via slow infusion over a period of 30 minutes. During this time and and for the following 30 min (60 minutes in total), the patient is closely monitored by the study staff to detect any possible allergic or infusion-related reactions. Another physical examination as well as vital signs and laboratory paramateres will be performed four hours after the end of the infusion. The next day (day 1) the Ferumoxtran-10 enhanced MRI scan is performed. Seven days after the Ferumoxtran-10 infusion, another physical examination and assessment of vital signs are performed as well as blood and urine samples are taken. Days 7 to 42: During this period, the planned prostatectomy (removal of the prostate) with extended removal of the lymph nodes in the pelvic area is performed. Prior to this surgery (on the same day or one day before) the same examinations are performed as on day 7. About 8 weeks after the surgery, blood and urine samples are assessed again and a normal MRT is also performed.
Endpoints
- Primary outcome:
- 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. Based on these parameters the sensitivity and specificity will be evaluated.
- Secondary outcome:
- - Number and regions of lymph node metastases present in the follow-up MRI in comparison to pre-surgery MRI (unenhanced and Ferrotran®-enhanced) - Frequency of occurrence and severity of abnormal findings in safety investigations (physical examination, vital signs, 12-lead ECG, clinical laboratory, concomitant medication, adverse events) - Percentage of subjects for whom the patient management plan would be changed based on the Ferrotran®-enhanced MRI
Study Design
- Purpose:
- Diagnostic
- Allocation:
- N/A (single arm study)
- Control:
-
- Uncontrolled/single arm
- Phase:
- III
- Study type:
- Interventional
- Mechanism of allocation concealment:
- No Entry
- Blinding:
- No
- Assignment:
- Single (group)
- Sequence generation:
- No Entry
- Who is blinded:
- No Entry
Recruitment
- Recruitment Status:
- Recruiting ongoing
- Reason if recruiting stopped or withdrawn:
- No Entry
Recruitment Locations
- Recruitment countries:
-
- Belgium
- Germany
- Netherlands
- Switzerland
- Number of study centers:
- Multicenter study
- Recruitment location(s):
-
- University medical center Universitätsspital Bern
- University medical center Universitätsklinikum Carl Gustav Carus Dresden
- University medical center Radboud University Medical Center Nijmegen
- University medical center Universitätsklinikum Köln Köln
- Medical center Canisius-Wilhelmina Ziekenhuis Nijmegen Nijmegen
- University medical center Universitätsklinikum Bonn Bonn
- University medical center Universitätsklinikum Schleswig-Holstein Lübeck
- Medical center Vivantes Am Urban Berlin
- University medical center Universitair Ziekenhuis Ghent
- University medical center Universitätsklinikum Düsseldorf Düsseldorf
- University medical center Universitätsklinikum Essen Essen
- University medical center Universitätsmedizin Mannheim Medizinische Fakultät Mannheim der Universität Heidelberg Mannheim
- University medical center Nederlands Kanker Instituut Antoni van Leeuwenhoek Amsterdam
- University medical center Universitätsklinikum Leipzig Leipzig
- University medical center Charité Benjamin-Franklin Berlin
Recruitment period and number of participants
- Planned study start date:
- 2020-02-29
- Actual study start date:
- 2020-05-27
- Planned study completion date:
- No Entry
- Actual Study Completion Date:
- No Entry
- Target Sample Size:
- 200
- Final Sample Size:
- No Entry
Inclusion Criteria
- Sex:
- Male
- Minimum Age:
- 18 Years
- Maximum Age:
- no maximum age
- Additional 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.
Exclusion Criteria
1. Any contraindication to MRI, as per standard criteria. 2. Any radiation therapyor 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
Addresses
Primary Sponsor
- Address:
- Saving Patients' Lives Medical B.V. (SPL Medical)Toernooiveld 1006525 EC NijmegenNetherlands
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
- Investigator Sponsored/Initiated Trial (IST/IIT):
- No
Contact for Scientific Queries
- Address:
- Saving Patients' Lives Medical B.V.(SPL Medical)Michael BerghahnToernooiveld 1006525 EC NijmegenNetherlands
- Telephone:
- 0031 24 303 10 90
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Contact for Public Queries
- Address:
- SPL-01-001 TeamSPL-01-001 TeamSchössergasse 1901067 DresdenGermany
- Telephone:
- 0351214440
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Principal Investigator
- Address:
- Saving Patients' Lives Medical B.V.(SPL Medical)Michael BerghahnToernooiveld 1006525 EC NijmegenNetherlands
- Telephone:
- 0031 24 303 10 90
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Sources of Monetary or Material Support
Commercial (pharmaceutical industry, medical engineering industry, etc.)
- Address:
- Saving Patients' Lives Medical B.V.(SPL Medical)Toernooiveld 1006525 EC NijmegenNetherlands
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Ethics Committee
Address Ethics Committee
- Address:
- Ethik-Kommission des Landes BerlinFehrbelliner Platz 110707 BerlinGermany
- Telephone:
- +49-30-902291220
- Fax:
- +49-30-90283383
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Vote of leading Ethics Committee
- Vote of leading Ethics Committee
- Date of ethics committee application:
- 2019-06-11
- Ethics committee number:
- 19/223 IV E 11
- Vote of the Ethics Committee:
- Approved
- Date of the vote:
- 2019-12-19
Further identification numbers
- Other primary registry ID:
- NCT04261777 - ClinicalTrials.gov
- EudraCT Number:
- 2018-004310-18
- Other secondary IDs:
- SPL-01-001 - sponsor-id - Saving Patients' Lives Medical B.V.
IPD - Individual Participant Data
- Do you plan to make participant-related data (IPD) available to other researchers in an anonymized form?:
- No
- IPD Sharing Plan:
- No Entry
Study protocol and other study documents
- Study protocols:
- No Entry
- Study abstract:
- No Entry
- Other study documents:
- Heesakkers RA, Jager GJ, Hövels 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. PMID: 19401573.
- D'Amico et al, 1998; Biochemical Outcome After Radical Prostatectomy, External Beam Radiation Therapy, or Interstitial Radiation Therapy for Clinically Localized Prostate Cancer
- Background literature:
- 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. PMID: 12815134.
- Heesakkers RA, Hövels AM, Jager GJ, van den Bosch HC, Witjes JA, Raat HP, Severens JL, Adang EM, van der Kaa CH, Fütterer 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. PMID: 18708295.
- Related DRKS studies:
- No Entry
Publication of study results
- Planned publication:
- No Entry
- Publikationen/Studienergebnisse:
- No Entry
- Date of first publication of study results:
- No Entry
- DRKS entry published for the first time with results:
- No Entry
Basic reporting
- Basic Reporting / Results tables:
- No Entry
- Brief summary of results:
- No Entry