This is a multi-centre, partially blinded, side-by-side comparator study to assess the safety and tolerability, feasibility, and potential added diagnostic and clinical value of using the FerroTrace® and FerroMag Sentinel Lymph Node Mapping (SLNM) System for mapping sentinel lymph nodes (SLNs) in subjects with gastric, gastric-oesophageal junction, and oesophageal cancers, consisting of a safety lead-in phase and an expansion phase.
This is a multi-centre, partially blinded, side-by-side comparator study to assess the safety and tolerability, feasibility, and potential added diagnostic and clinical value of using the FerroTrace® and FerroMag SLNM System for mapping SLNs in subjects with gastric, gastric-oesophageal junction, and oesophageal cancers, consisting of a safety lead-in phase and an expansion phase. A safety lead-in phase will be adopted to determine the optimal dose for the expansion phase. For the safety lead-in phase, a minimum of 6 eligible subjects will undergo a FerroTrace® injection followed by Research magnetic resonance imaging (MRI) to visualise and assess SLNs. Safety will be monitored for 7 to 14 days, and will include reviews of safety, pharmacokinetics, image quality data from MRI pre and post FerroTrace® injection, and MRI SLN identification feasibility. Dose escalation/de-escalation may be performed using a 3+3 design if required. Upon successful completion of the safety lead-in phase, a dose of FerroTrace® will be selected for use in the expansion phase. The expansion phase will consist of three cohorts of subjects (gastric, gastric-oesophageal junction, oesophageal cancers). Eligible subjects will undergo a FerroTrace® injection followed by a Research MRI to visualise and assess SLNs. If applicable a post neoadjuvant therapy Research MRI may be performed. The Research MRIs will be blinded to the multi-disciplinary team (MDT). During surgery a comparator product, Indocyanine green (ICG) with a near-infrared camera, will be used to identify fluorescent lymph nodes and in histopathology on ex-vivo specimens a magnetometer (FerroMag) will identify SLNs. The identification and location of all identified SLNs will be recorded, and all will be examined with fine serial sectioning and immunochemistry by pathology. The study will assess disease free and overall survival and its correlation to histopathology and SLN location.
Study Type
INTERVENTIONAL
Allocation
NA
FerroTrace will be injected peri-tumorally during the surgeons staging endoscopy, with an MRI conducted 12h to 28 days after injection. The MRI will be blinded to the clinical team and will assess the location of the primary draining lymph nodes (sentinel lymph nodes or SLNs). Patients will proceed to standard of care neoadjuvant therapy and/or surgery. During surgery, indocyanine green (ICG) will be used to identify draining lymph nodes. Following surgery, pathologists will use FerroMag to identify SLNs which will undergo standard H\&E assessment, and if negative ultras-staging (fine serial slice and immunochemistry).
Royal Adelaide Hospital
Adelaide, South Australia, Australia
Flinders Medical Centre
Bedford Park, South Australia, Australia
Austin Hospital
Heidelberg, Victoria, Australia
Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia
SLN detection rate
SLN detection rate and number of SLNs per subject using MRI and FerroMag following FerroTrace® injection and concordance between MRI and FerroMag
Time frame: Up to 14 days post surgery
Ultra-staging diagnostic value
Positive diagnostic value of FerroTrace® SLN mapping and SLN histopathological ultra-staging defined as the number of additional node negative (pN0/ypN0) subjects who are diagnosed with isolated tumor cells (pN0i+/ypN0i+), micro-metastasis (pN1mi/ypN1mi) and node positive (pN1/ypN1) by SLN ultra-staging plus standard of care histopathology versus standard of care histopathology only.
Time frame: Up to 14 days post surgery
Surgical quality
Percentage of subjects with an SLN identified on MRI that is/are untreated by radiotherapy or surgery.
Time frame: Up to 14 days post surgery
Rate of Adverse Events (AEs)
Incidence, nature, severity, and relatedness to FerroMag or FerroTrace® of AEs and Serious Adverse Events (SAEs), changes of laboratory parameters, vital signs, and ECG results per NCI CTCAE v5.0
Time frame: The earlier of 28 days post FerroTrace injection or commencement of neoadjuvant therapy or surgery
SLN Location Disease Free Survival
Disease free survival rates of subjects categorised by SLN location (MRI identified SLNs all treated/removed by radiotherapy/surgery versus some SLNs not treated/removed).
Time frame: Up to 5 years post surgery
SLN Ultra-staging Disease Free Survival
Disease free survival rates of subjects categorised by histopathology after SLN ultra-staging.
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Purpose
TREATMENT
Masking
NONE
Enrollment
60
Time frame: Up to 5 years post surgery
SLN Location Overall Survival
Overall survival rates of subjects categorised by SLN location (MRI identified SLNs all treated/removed by radiotherapy/surgery versus some SLNs not treated/removed)
Time frame: Up to 5 years post surgery
SLN Ultra-staging Overall Survival
Overall survival rates of subjects categorised by histopathology after SLN ultra-staging
Time frame: Up to 5 years post surgery