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Magnetic Sentinel Lymph Node Mapping in Upper Gastro-Intestinal Cancer: A Feasibility Clinical Investigation (MAGMAP)

Primary Purpose

Gastric Cancer, Esophageal Cancer

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
FerroTrace® and FerroMag Sentinel Lymph Node Mapping (SLNM) System
Sponsored by
Ferronova Pty Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastric Cancer focused on measuring Sentinel lymph node

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Subject is capable of understanding and has provided written informed consent. Subject over 18 years of age and is fit to complete the study in the opinion of the investigator. Subject with a previously untreated histopathology confirmed diagnosis of gastric, gastric-oesophageal junction, oesophageal cancer and at the time of enrolment is expected to undergo curative-intent surgery. Females of childbearing potential must be willing to use methods of contraception as deemed adequate by the Investigator to be eligible for, and continue participation in, the study. In the opinion of the Investigator, the subject can complete the study in compliance with the Investigational Plan and is able to comply with the requirements of the Investigational Plan. Subjects with an Eastern Cooperative Oncology Group (ECOG) performance status of Grade 0-2. Additional tumour specific inclusion criteria for subjects in expansion cohorts as directed by the Sponsor. Exclusion Criteria: Subject has distant metastasis as detected on CT, PET, ultrasound guided fine needle aspiration (FNA), or cytology prior to enrolment. Subject started neoadjuvant therapy before informed consent, or prior to FerroTrace® administration. Subject has received a Feraheme® (ferumoxytol) injection within the past 180 days. Subject has a known or suspected history of allergies, hypersensitivity, or intolerances as follows: Iron compounds Polyacrylamide Polyethylene glycol (PEG) or has had an anaphylactic reaction to the Pfizer or Moderna COVID vaccines Iodine compounds Known or suspected hypersensitivity to FerroTrace®, or to any ingredients of FerroTrace®. Subject known to have haemochromatosis. Subjects with other known iron metabolism disorder(s) if the Investigator determines the subject is at a higher risk of iron toxicity. Subjects who at the time of enrolment are pregnant or lactating, or from the time of enrolment through to 14 days after injection of the study dose are trying to become pregnant, planning to impregnate a partner, or planning to donate sperm. Subject has one or more absolute contraindications to MRI scanning as per Investigator judgement. Subjects with an estimated glomerular filtration rate (eGFR) of < 30 mL/min/1.73m2. Subject has inability or unwillingness to comply with all follow-ups through to the end of the study, and/or unwilling to allow review of medical records in accordance with local regulatory requirements at time of consent. Investigator determines that the subject is not suitable for study participation for any other reason. Subject received an investigational product (IP) within 30 days of FerroTrace® administration unless agreed by the sponsor. Subjects have hyperthyroidism or benign thyroid nodules

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Other

    Arm Label

    Single Arm

    Arm Description

    Eligible subjects will undergo their normal standard of care treatment pathway with the added interventions described below.

    Outcomes

    Primary Outcome Measures

    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
    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.
    Surgical quality
    Percentage of subjects with an SLN identified on MRI that is/are untreated by radiotherapy or surgery.

    Secondary Outcome Measures

    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
    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).
    SLN Ultra-staging Disease Free Survival
    Disease free survival rates of subjects categorised by histopathology after SLN ultra-staging.
    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)
    SLN Ultra-staging Overall Survival
    Overall survival rates of subjects categorised by histopathology after SLN ultra-staging

    Full Information

    First Posted
    June 2, 2023
    Last Updated
    June 2, 2023
    Sponsor
    Ferronova Pty Ltd
    Collaborators
    Royal Adelaide Hospital, Austin Health, Flinders Medical Centre, Peter MacCallum Cancer Centre, Australia, South Australian Health and Medical Research Institute
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05899985
    Brief Title
    Magnetic Sentinel Lymph Node Mapping in Upper Gastro-Intestinal Cancer: A Feasibility Clinical Investigation
    Acronym
    MAGMAP
    Official Title
    Magnetic Sentinel Lymph Node Mapping in Upper Gastro-Intestinal Cancer: A Feasibility Clinical Investigation
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 2023 (Anticipated)
    Primary Completion Date
    February 2025 (Anticipated)
    Study Completion Date
    February 2030 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Ferronova Pty Ltd
    Collaborators
    Royal Adelaide Hospital, Austin Health, Flinders Medical Centre, Peter MacCallum Cancer Centre, Australia, South Australian Health and Medical Research Institute

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    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.
    Detailed Description
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Gastric Cancer, Esophageal Cancer
    Keywords
    Sentinel lymph node

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Single Group Assignment
    Model Description
    Multi-centre, partially blinded, side-by-side comparator study
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    60 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Single Arm
    Arm Type
    Other
    Arm Description
    Eligible subjects will undergo their normal standard of care treatment pathway with the added interventions described below.
    Intervention Type
    Combination Product
    Intervention Name(s)
    FerroTrace® and FerroMag Sentinel Lymph Node Mapping (SLNM) System
    Intervention Description
    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).
    Primary Outcome Measure Information:
    Title
    SLN detection rate
    Description
    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
    Title
    Ultra-staging diagnostic value
    Description
    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
    Title
    Surgical quality
    Description
    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
    Secondary Outcome Measure Information:
    Title
    Rate of Adverse Events (AEs)
    Description
    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
    Title
    SLN Location Disease Free Survival
    Description
    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
    Title
    SLN Ultra-staging Disease Free Survival
    Description
    Disease free survival rates of subjects categorised by histopathology after SLN ultra-staging.
    Time Frame
    Up to 5 years post surgery
    Title
    SLN Location Overall Survival
    Description
    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
    Title
    SLN Ultra-staging Overall Survival
    Description
    Overall survival rates of subjects categorised by histopathology after SLN ultra-staging
    Time Frame
    Up to 5 years post surgery
    Other Pre-specified Outcome Measures:
    Title
    FerroTrace and ICG Concordance
    Description
    Nodal yield of ICG nodal mapping and concordance rate of FerroTrace® identified SLNs versus ICG identified nodes, categorised by subjects' neoadjuvant therapy type if applicable
    Time Frame
    Up to 14 days post surgery
    Title
    FerroTrace enhanced MRI Diagnosis
    Description
    Specificity and sensitivity of FerroTrace® enhanced MRI in detecting tumour deposits in the SLNs versus CT, positron emission tomography (PET), and standard of care histopathology
    Time Frame
    Up to 14 days post surgery
    Title
    FerroTrace enhanced MRI Response
    Description
    Specificity and sensitivity of FerroTrace® enhanced MRI in detecting response to neoadjuvant therapy in lymph nodes
    Time Frame
    Up to 14 days post surgery

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Subject is capable of understanding and has provided written informed consent. Subject over 18 years of age and is fit to complete the study in the opinion of the investigator. Subject with a previously untreated histopathology confirmed diagnosis of gastric, gastric-oesophageal junction, oesophageal cancer and at the time of enrolment is expected to undergo curative-intent surgery. Females of childbearing potential must be willing to use methods of contraception as deemed adequate by the Investigator to be eligible for, and continue participation in, the study. In the opinion of the Investigator, the subject can complete the study in compliance with the Investigational Plan and is able to comply with the requirements of the Investigational Plan. Subjects with an Eastern Cooperative Oncology Group (ECOG) performance status of Grade 0-2. Additional tumour specific inclusion criteria for subjects in expansion cohorts as directed by the Sponsor. Exclusion Criteria: Subject has distant metastasis as detected on CT, PET, ultrasound guided fine needle aspiration (FNA), or cytology prior to enrolment. Subject started neoadjuvant therapy before informed consent, or prior to FerroTrace® administration. Subject has received a Feraheme® (ferumoxytol) injection within the past 180 days. Subject has a known or suspected history of allergies, hypersensitivity, or intolerances as follows: Iron compounds Polyacrylamide Polyethylene glycol (PEG) or has had an anaphylactic reaction to the Pfizer or Moderna COVID vaccines Iodine compounds Known or suspected hypersensitivity to FerroTrace®, or to any ingredients of FerroTrace®. Subject known to have haemochromatosis. Subjects with other known iron metabolism disorder(s) if the Investigator determines the subject is at a higher risk of iron toxicity. Subjects who at the time of enrolment are pregnant or lactating, or from the time of enrolment through to 14 days after injection of the study dose are trying to become pregnant, planning to impregnate a partner, or planning to donate sperm. Subject has one or more absolute contraindications to MRI scanning as per Investigator judgement. Subjects with an estimated glomerular filtration rate (eGFR) of < 30 mL/min/1.73m2. Subject has inability or unwillingness to comply with all follow-ups through to the end of the study, and/or unwilling to allow review of medical records in accordance with local regulatory requirements at time of consent. Investigator determines that the subject is not suitable for study participation for any other reason. Subject received an investigational product (IP) within 30 days of FerroTrace® administration unless agreed by the sponsor. Subjects have hyperthyroidism or benign thyroid nodules
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Markus Trochsler
    Phone
    +61 08 82226750
    Email
    Markus.Trochsler@sa.gov.au
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Joe El-Aklouk
    Organizational Affiliation
    Ferronova Pty Ltd
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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