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Trial registered on ANZCTR


Registration number
ACTRN12621000748819
Ethics application status
Approved
Date submitted
12/05/2021
Date registered
15/06/2021
Date last updated
27/05/2024
Date data sharing statement initially provided
15/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Magnetic and Indocyanine Green (ICG) Sentinel Lymph Node Mapping in Colorectal Cancer:
A Feasibility and Validity Clinical Trial
Scientific title
Magnetic and Indocyanine Green (ICG) Sentinel Lymph Node Mapping in Colorectal Cancer:
A Feasibility and Validity Clinical Trial
Secondary ID [1] 304200 0
SMF-2
Universal Trial Number (UTN)
Trial acronym
MAGICSENT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal cancer 321887 0
Condition category
Condition code
Cancer 319618 319618 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Surgery 319938 319938 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a multi centre, open label, side-by-side comparator study to assess the safety, feasibility and validity of lymphatic staging using the standard of care lymphadenectomy and histopathology process compared with using investigational products in combination being FerroTrace and ICG for mapping sentinel lymph nodes (SLNs), as an adjunct to the standard of care lymphadenectomy in subjects with colorectal cancer. The study will also investigate the feasibility of assessing lymph nodes for metastasis using FerroTrace enhanced MRI in rectal cancer subjects and in colon cancer subjects at the discretion of the Investigator, with MRI performed when the Investigator believes bowel motion artefacts will not affect the MRI or does not expose the patients to unacceptable COVID risk. A maximum of 40 subjects will be enrolled. Eligible subjects will receive a single dose of 0.4-0.5ml (27mg Fe) of FerroTrace and a single dose of 0.4-0.5ml of ICG(1.25mg) administered via four equal volume endoscopic peri-tumoural submucosal injections each of 1/4 of the dose, administered either separately for subjects part of the MRI protocol, or together during surgery for those not including MRI. Subjects with the optional MRI will receive a pre-injection MRI of the pelvis followed by the endoscopic FerroTrace™ injections, and a post-injection MRI of the pelvis 2 – 30 h after injection. During surgery, subjects will receive the ICG injections. Subjects not including the MRI will receive the FerroTrace™/ICG injections during surgery. For all subjects, the standard of care surgery and lymphadenectomy will be performed. At the surgeon’s discretion, a near infrared (NIR) surgical camera may be used to identify and remove extra-regional LNs they assess to contain FerroTrace and ICG. An ex vivo survey of the excised specimen using a magnetometer probe and near infrared camera will be performed to locate specimen SLNs. Histopathology will be as per standard of care for all LNs in the lymphadenectomy specimen, plus more detailed ultra-staging of SLNs using serial slicing and immunochemistry. The fidelity of the intervention is ensured by only specialists with endoscopy accreditation being used for the injection of the investigational product, and a video being recorded of the injection for monitoring purposes.
Intervention code [1] 320531 0
Diagnosis / Prognosis
Intervention code [2] 320532 0
Treatment: Surgery
Comparator / control treatment
The standard of care lymphadenectomy and histopathology process consists of the surgical removal of a specimen (Complete Mesocolic Excision for colon cancer and Total Mesorectal Excision in rectal cancer), followed by the sampling of lymph nodes from the specimen by histopathology and an examination of each of the sampled nodes using Hematoxylin & Eosin as per protocol recommendations of the Royal College of Pathologists of Australasia (RCPA) for structured reporting of colorectal cancer and staged as per the 8th edition of the AJCC Cancer Staging Manual (2017)
Control group
Active

Outcomes
Primary outcome [1] 327493 0
Composite outcome - Safety: Percentage of subjects with adverse events overall, and by severity and relatedness, graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Timepoint [1] 327493 0
Day -1 - the day before surgery
Day 0 - the day of surgery
Day 14 - 14 days after surgery
Secondary outcome [1] 395358 0
Composite outcome: Feasibility and timing of MRI following FerroTrace injection for pre-operative SLN localization in colon and rectal cancer.

Assessed by comparing MRI localisation of SLNs versus surgical localisation of SLNs using a magnetometer and NIR camera
Timepoint [1] 395358 0
Day -1 - the day before surgery
Day 0 - surgery
Secondary outcome [2] 395359 0
Feasibility and timing of FerroTrace and ICG injection for intra-operative SLN identification in colon and rectal cancer.

Assessed by the proportion of subjects with successful surgical localisation of at least one SLN using a magnetometer and NIR camera.
Timepoint [2] 395359 0
Day 0 - surgery
Secondary outcome [3] 395360 0
Feasibility and timing of pre-operative MRI following FerroTrace injection to detect tumour deposits in the SLN in colon cancer and rectal cancer.

Assessed by the proportion of subjects with cN1 MRI assessment of SLNs versus the pN0i+, pN1mi and pN1 histopathology assessments of the same SLNs
Timepoint [3] 395360 0
Day 14 - 14 days after surgery when pathology results are available
Secondary outcome [4] 395361 0
Specificity and sensitivity of SLN pathology versus standard of care lymphadenectomy pathology in colon and rectal cancer.

Assessed the proportion of subjects with pN0i+, pN1mi and pN1 staging from the histopathology of SLNs only versus pN0i+, pN1mi and pN1 staging of the standard histopathology of all lymph nodes in the excised specimen.
Timepoint [4] 395361 0
Day 14 - 14 days after surgery when pathology results are available
Secondary outcome [5] 395362 0
Diagnostic value of SLN Mapping and histopathological ultra-staging defined as the number of participants who are diagnosed as pN0i+, pN1mi and pN1 by sentinel lymph node mapping / sampling plus lymphadenectomy versus lymphadenectomy only in colon and rectal cancer.

Assessed by the total number of subjects with pN0i+, pN1mi and pN1 from the histopathology of SLNs plus the standard pathology on all lymph nodes versus the total number of subjects with pN0i+, pN1mi and pN1 from the standard histopathology on all lymph nodes in the excised specimen
Timepoint [5] 395362 0
Day 14 - 14 days after surgery when pathology results are available

Eligibility
Key inclusion criteria
1. Subject has provided written informed consent.
2. Subject is between 18 and 75 years of age (inclusive) at the time of providing informed consent.
3. Subject with a confirmed diagnosis of primary colon or rectal cancer with no distal metastasis.
4. Subject is scheduled for lymphadenectomy as part of the surgical plan.
5. Subject has a clinical negative node status (i.e., cN0) at the time of providing informed consent.
6. If applicable, subjects must be willing to use methods of contraception as deemed adequate by the Investigator to be eligible for, and continue participation in, the study.
7. In the opinion of the Investigator, the subject can complete the study in compliance with the protocol and is able to comply with the requirements of the study protocol.
8. Subjects with an ECOG performance status of Grade 0–2.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Subject has had preoperative radiation therapy to the pelvis or abdomen.
2. Subject has received a Feraheme® (ferumoxytol) injection within the past 180 days.
3. Subject has a known or suspected history of allergies, hypersensitivity, or intolerances as follows:
a. Iron compounds
b. Polyacrylamide
c. PEG
d. Iodine compounds
e. Known or suspected hypersensitivity to the investigational product, or to any ingredients of the investigational product.
4. Subject known to have haemochromatosis.
5. Subject has a co-morbid condition with an estimated life expectancy of <180 days at the time of consent.
6. Subjects who are pregnant, trying to become pregnant, or lactating at time of screening.
7. Subject has participated in another investigational drug study within 30 days of scheduled surgery.
8. Subject considered for inclusion in the MRI cohort has one or more absolute contraindications to MRI scanning as per Investigator judgement.
9. Subjects with an eGFR of < 30 ml/min/1.73m2.
10. Subject has inability or unwillingness to comply with all follow-up 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.
11. Investigator determines that the subject is not suitable for study participation for any other reason (e.g., Subject has had previous pelvic surgery, or lymphatic function that is impaired in the Investigator’s judgment)

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
All participants receive the comparator standard of care, as well as the intervention.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
A maximum of 40 subjects will be included in this study.

The planned number of subjects is considered appropriate to make an initial determination on the safety and efficacy of FerroTrace and ICG for sentinel lymph node mapping in colorectal cancer.

The Bayesian method will be applied for interim toxicity monitoring. Toxicity is defined as any CTCAE v5.0 Grade III or greater AE attributable to FerroTrace injection. We assume as a priori, p(TOX) ~ ß (0.3, 0.7). The trial will be stopped early due to toxicity if Pr(p(TOX)> 0.30 | data) >0.70, i.e., we will stop the trial for new subject enrolment if we determine that there is >70% chance that the toxicity rate is >30%. The toxicity monitoring rule will be applied starting from the 5th subject, and then in cohort sizes of 5

The study will be stopped if 3 or more of the first 5 subjects, 5 or more of the first 10 subjects, 6 or more of the first 15 subjects, 8 or more of the first 20 subjects, 9 or more of the first 25 subjects, 11 or more of the first 30 subjects, or 13 or more of the first 35 subjects have experienced FerroTrace related CTCAE Grade III or worse adverse events.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
4/02/2022
Actual
1/03/2022
Date of last participant enrolment
Anticipated
31/12/2024
Actual
Date of last data collection
Anticipated
30/06/2024
Actual
Sample size
Target
40
Accrual to date
19
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 19431 0
Liverpool Hospital - Liverpool
Recruitment postcode(s) [1] 34013 0
2170 - Liverpool

Funding & Sponsors
Funding source category [1] 308573 0
Government body
Name [1] 308573 0
MTPConnect on behalf of the Medical Research Future Fund
Country [1] 308573 0
Australia
Funding source category [2] 308585 0
Commercial sector/Industry
Name [2] 308585 0
Ferronova Pty Ltd
Country [2] 308585 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Ferronova Pty Ltd
Address
MM3-02, MM Building, UniSA
Mawson Lakes Blvd
Mawson Lakes SA 5095
Australia
Country
Australia
Secondary sponsor category [1] 309429 0
None
Name [1] 309429 0
Address [1] 309429 0
Country [1] 309429 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308515 0
Bellberry HREC
Ethics committee address [1] 308515 0
Ethics committee country [1] 308515 0
Australia
Date submitted for ethics approval [1] 308515 0
12/04/2021
Approval date [1] 308515 0
26/05/2021
Ethics approval number [1] 308515 0
2021ETH00612

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 110974 0
Dr Andrew Gilmore
Address 110974 0
Liverpool Hospital
75 Elizabeth Street
LIVERPOOL NSW 2170
Country 110974 0
Australia
Phone 110974 0
+61 2 8738 3000
Fax 110974 0
Email 110974 0
[email protected]
Contact person for public queries
Name 110975 0
Megan Ford
Address 110975 0
1 Campbell St,
Liverpool NSW 2170
Country 110975 0
Australia
Phone 110975 0
+61 2 8738 3000
Fax 110975 0
Email 110975 0
[email protected]
Contact person for scientific queries
Name 110976 0
Andrew Gilmore
Address 110976 0
Liverpool Hospital
75 Elizabeth Street
LIVERPOOL NSW 2170
Country 110976 0
Australia
Phone 110976 0
+61 2 8738 3000
Fax 110976 0
Email 110976 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
De-identified data will be available to the Sponsor and Investigators to enable publication, or as part of any regulatory requirements. It will not be available other than for these purposes.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.