Clinical trial NCT05899985: Magnetic Sentinel Lymph Node Mapping in Upper Gastro-Intestinal Cancer: A Feasibility Clinical Investigation
Official title: Magnetic Sentinel Lymph Node Mapping in Upper Gastro-Intestinal Cancer: A Feasibility Clinical Investigation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Gastric Cancer
Esophageal Cancer
Keywords: Sentinel lymph node
Lead sponsor: Ferronova Pty Ltd
Sponsor class: INDUSTRY
Collaborators: name: Royal Adelaide Hospital
name: Austin Health
name: Flinders Medical Centre
name: Peter MacCallum Cancer Centre, Australia
name: South Australian Health and Medical Research Institute
First posted: 2023-06-12
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Multi-centre, partially blinded, side-by-side comparator study
Primary purpose: TREATMENT

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.

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:

  1. Iron compounds
  2. Polyacrylamide
  3. Polyethylene glycol (PEG) or has had an anaphylactic reaction to the Pfizer or Moderna COVID vaccines
  4. Iodine compounds
  5. 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

Primary outcomes:
measure: SLN detection rate
timeFrame: Up to 14 days post surgery
measure: Ultra-staging diagnostic value
timeFrame: Up to 14 days post surgery
measure: Surgical quality
timeFrame: Up to 14 days post surgery
Secondary outcomes:
measure: Rate of Adverse Events (AEs)
timeFrame: The earlier of 28 days post FerroTrace injection or commencement of neoadjuvant therapy or surgery
measure: SLN Location Disease Free Survival
timeFrame: Up to 5 years post surgery
measure: SLN Ultra-staging Disease Free Survival
timeFrame: Up to 5 years post surgery
measure: SLN Location Overall Survival
timeFrame: Up to 5 years post surgery
measure: SLN Ultra-staging Overall Survival
timeFrame: Up to 5 years post surgery
Other outcomes:
measure: FerroTrace and ICG Concordance
timeFrame: Up to 14 days post surgery
measure: FerroTrace enhanced MRI Diagnosis
timeFrame: Up to 14 days post surgery
measure: FerroTrace enhanced MRI Response
timeFrame: Up to 14 days post surgery
Locations:
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
Study officials:
affiliation: Ferronova Pty Ltd
name: Joe El-Aklouk
role: STUDY_DIRECTOR
References: