Exploring an Alternative Pre-operative SLN Mapping Method Using a Magnetic Tracer and MRI for Melanoma Patients (SCARLETT)

Exploring an Alternative Pre-operative Sentinel Lymph Node Mapping Method Using a Magnetic Tracer and MRI for Melanoma Patients

Sentinel lymph node biopsy (SLNB) is crucial in the management of malignant melanoma treatment and is currently performed by pre-operatively inject a colloid nanomaterial labeled with Technetium (99mTc) as radioactive tracer. Intra-operatively, Patent Blue (PB) will be injected to improve the visualization of the lymphatic tract. However, current pre-operative SLN mapping technique is associated with disadvantages as radiation exposure for both patients and health care staff and logistic challenges, because of time constraints due to short half-live time of 99mTc.

Superparamagnetic iron oxide (SPIO) is a non-radioactive technique using a magnetic tracer (Magtrace® (Endomagnetics Ltd.)) to identify SLNs. Several studies showed that SPIO is non-inferior to dual tracing with 99mTc and PB in breast cancer patients. SPIO is expected to be non-inferior to dual tracing with 99mTc and PB in melanoma patients. However, further research is needed to demonstrate the use of SPIO in pre-operative MRI scanning.

The primary objective of this study is to evaluate the feasibility and diagnostic accuracy of pre-operative MRI scanning using SPIO compared to lymphoscintigraphy (LS) and single-photon emission computed tomography/computed tomography (SPECT/CT) using 99mTc for identifying SLN status in melanoma patients.

Study Overview

• Status: Recruiting
• Conditions: Melanoma
• Intervention / Treatment: Diagnostic test: Diagnostic Test: Sentinel node mapping using MRI

Detailed Description

Rationale: Sentinel lymph node biopsy (SLNB) is crucial in the management of malignant melanoma treatment and is currently performed by pre-operatively inject a colloid nanomaterial labeled with Technetium (99mTc) as radioactive tracer. Intra-operatively, Patent Blue (PB) will be injected to improve the visualization of the lymphatic tract. However, current pre-operative SLN mapping technique is associated with disadvantages as radiation exposure for both patients and health care staff and logistic challenges, because of time constraints due to short half-live time of 99mTc.

Superparamagnetic iron oxide (SPIO) is a non-radioactive technique using a magnetic tracer (Magtrace® (Endomagnetics Ltd.)) to identify SLNs. Several studies showed that SPIO is non-inferior to dual tracing with 99mTc and PB in breast cancer patients. SPIO is expected to be non-inferior to dual tracing with 99mTc and PB in melanoma patients. However, further research is needed to demonstrate the use of SPIO in pre-operative MRI scanning.

Objective: The primary objective of this study is to evaluate the feasibility and diagnostic accuracy of pre-operative MRI scanning using SPIO compared to lymphoscintigraphy (LS) and single-photon emission computed tomography/computed tomography (SPECT/CT) using 99mTc for identifying SLN status in melanoma patients. A secondary objective is to assess the feasibility and diagnostic accuracy of SPIO/magnetometer (Sentimag®, Endomagnetics Ltd.) in comparison with dual trace gold standard (99mTc and PB) in SLN procedures in melanoma patients.

Study design: A prospective single-arm feasibility study will be performed at the department of Surgical oncology at Zuyderland Medical Center Sittard, the Netherlands.

Study population: Adult patients (≥18 years) with primary melanoma stage I-II and an indication for wide local excision (1 cm) and SLN procedure will be included in the study.

Intervention (if applicable): All patients will undergo lymphatic mapping with a SPIO tracer (Magtrace®), 99mTc and PB.

Main study parameters/endpoints: The concordance in SLN detection rate (sensitivity and specificity) of SPIO/MRI and LS and SPECT/CT using 99mTc.

The concordance in SLN detection rate (sensitivity and specificity) of SPIO/magnetometer and the gold standard dual trace technique using 99mTc/Gamma probe and PB. Additionally, the number of post-injection (skin) reactions, complication and adverse events will be noted.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: James van Bastelaar, MD, PhD; Phone Number: 0884597777; Email: j.vanbastelaar@zuyderland.nl
• Study Contact Backup: Name: Loeki Aldenhoven, MSc; Phone Number: 0884597777; Email: l.aldenhoven@zuyderland.nl

Study Locations

• Netherlands
  • Limburg
    • Sittard, Limburg, Netherlands, 6162BG
      • Recruiting
      • Zuyderland Medical Center
      • Contact: James van Bastelaar, MD, PhD; Phone Number: 0031884597777; Email: j.vanbastelaar@zuyderland.nl
      • Contact: Loeki Aldenhoven, MSc; Phone Number: 0031884597777; Email: l.aldenhoven@zuyderland.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients ≥18 years of age at the time of consent;
• Histological confirmed melanoma (patient must have primary cutaneous melanoma with Breslow thickness ≥ 0.8-2.0mm with or without ulceration or <0.8mm with ulceration (pT1b - pT2b, AJCC 8th edition));
• Indication for wide local excision (margin 1 cm) and SLN procedure;
• Patients should be willing and able to provide informed consent.

Exclusion Criteria:

• Intolerance/hypersensitivity to 99mTc-nanocolloid, PB, iron or dextran compounds;
• Iron overload disease;
• Pregnant or breast-feeding women;
• Previous surrounded lymph node surgery;
• Patients with head and neck melanomas;
• Standard MRI exclusion criteria;
• Implantable (electrical) devices (e.g. pacemaker, cochlear implants, neurostimulator);
• Any other metal implants;
• Claustrophobia;
• MR-incompatible prosthetic heart valves;
• Patients who are unable or refuse to provide informed consent.

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: Melanoma patients; All patients will undergo lymphatic mapping with SPIO, 99mTc and PB.	Diagnostic test: Diagnostic Test: Sentinel node mapping using MRI; Sentinel lymph node mapping in melanoma patients using a magnetic tracer and MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The diagnostic accuracy of SPIO/MRI and LS+SPECT/CT and 99mTc to identify SLN	The diagnostic accuracy of SPIO/MRI and LS+SPECT/CT and 99mTc to identify SLN will be expressed as sensitivity and specificity, and positive and negative predictive values, including their 95% exact binomial confidence intervals. MRI image analyses will be performed by two independent professionals.	Before surgery (MRI scanning and scintigraphy)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The diagnostic accuracy of SPIO/magnetometer and PB, 99mTc and Gamma probe	The diagnostic accuracy of SPIO/magnetometer and PB, 99mTc and Gamma probe will be expressed as sensitivity and specificity, and positive and negative predictive values, including their 95% exact binomial confidence intervals .	During SLNB (surgery)
Comparison between 99mTc injection + LS + SPECT/CT time vs SPIO injection + MRI	Time/duration of 99mTc injection + LS + SPECT/CT and time/duration of SPIO injection + MRI will be compared	During SLNB (surgery)
Number of post-injection (skin) reactions, complication and adverse events	Descriptive only	At 10-14 days and at 3 months after the procedure

Collaborators and Investigators

• Sponsor: Zuyderland Medisch Centrum

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Anticipated): September 1, 2024
• Study Completion (Anticipated): September 1, 2024

Study Registration Dates

• First Submitted: November 3, 2021
• First Submitted That Met QC Criteria: November 22, 2021
• First Posted (Actual): December 6, 2021

Study Record Updates

• Last Update Posted (Estimate): January 26, 2023
• Last Update Submitted That Met QC Criteria: January 24, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: MRI; Melanoma; Sentinel lymph node; Magnetic tracer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: METCZ20210156

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