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Trial registered on ANZCTR


Registration number
ACTRN12621000126819
Ethics application status
Approved
Date submitted
18/11/2020
Date registered
8/02/2021
Date last updated
30/11/2021
Date data sharing statement initially provided
8/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety and Efficacy of MagSense Human Epidermal Growth Factor Receptor 2 (HER2) Test Reagent in Breast Cancer Lymph Node Magnetic Reasonance Imaging (MRI) and Magnetic Relaxometry (MRX).
Scientific title
A Phase I Study Investigating the Safety and Efficacy of the MagSense (Trademark) Human Epidermal Growth Factor Receptor 2 (HER2) Test Reagent Using Magnetic Resonance Imaging and the MagSense (Trademark) Instrument in Subjects with HER2-positive Breast Cancer to Test for Ipsilateral Lymph Node Involvement
Secondary ID [1] 302650 0
Imagion Protocol number IBI010103
Universal Trial Number (UTN)
U1111-1256-8388
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 319633 0
Condition category
Condition code
Cancer 317572 317572 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
MagSense (Trademark) Human Epidermal Growth Factor Receptor 2 (HER2) Test Reagent (MSH2TR) will be administered once only as a subareolar injection (the pigmented area around the nipple) near or around the tumour; at dose of 30mg as either a single 3mL injection or divided into 3 x 1mL injections next to each other if the volume of injection causes discomfort, after the baseline MRI and approximately 72 hours prior to the scheduled biopsy. If 30mg is not tolerated by more than 2 subjects in the first cohort of 6 subjects, MSH2TR will be administered at 20mg either a single injection or divided into 2 x 1ml injections next to each other if the volume of injection causes discomfort.
Intervention code [1] 318994 0
Diagnosis / Prognosis
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 325615 0
Incidence and severity of adverse events via clinical examination and classifed by CTCAE v5.0 criteria
Timepoint [1] 325615 0
Days 1, 2, 3, 4, 7 and 28
Primary outcome [2] 326191 0
Incidence of serious adverse events via clinical examination & review of medical records and classified by CTCAE v5.0 criteria
Timepoint [2] 326191 0
Days 1, 2, 3, 4, 7 and 28
Primary outcome [3] 326192 0
Clinically significant changes from baseline measured by haematology (blood sample) and chemistry parameters (blood and urine samples).
Timepoint [3] 326192 0
Screening and on days 1, 2 and 4.
Secondary outcome [1] 388571 0
Lymph node detection rate of the test reagent assessed by iron and HER2 histological staining of the lymph node biopsy samples (colocalisation).
Timepoint [1] 388571 0
Day 4
Secondary outcome [2] 388577 0
Lymph node detection rate assessed by MRI scan of the upper body (lymph nodes).
Timepoint [2] 388577 0
On Days 2 and 4.
Secondary outcome [3] 388578 0
Lymph node detection rate assessed by MRX imaging of the lymph node biopsy samples.
Timepoint [3] 388578 0
Day 4
Secondary outcome [4] 390436 0
Lymph node detection rate identified by MRX imaging of the lymph nodes compared with MRI imaging and the histological findings of the lymph nodes (Iron staining and HER2 status).
Timepoint [4] 390436 0
Day 4
Secondary outcome [5] 390459 0
Incidence of injection site reactions by clinical examination and classified by CTCAE v5.0 criteria (additional primary outcome).
Timepoint [5] 390459 0
At Days 1, 2, 3, 4, 7 and 28 days post test reagent administration

Eligibility
Key inclusion criteria
To be eligible for study entry subjects must satisfy all of the following criteria
* Female subjects
* Written informed consent provided for participation in the study;
* In the opinion of investigator, willing and able to comply with required study procedures;
* Histologically confirmed HER2-positive primary breast cancer;
* No prior treatment for breast cancer including surgery, radiotherapy, or systemic treatment;
* In the investigator’s judgment from previous clinical, pathological, or imaging evidence have a likelihood of having at least 1 lymph node metastasis;
* Scheduled for surgical intervention with a SLNB and/or ALND as guided by technetium-99m (99mTc) diagnostic agent injection procedure being part of the surgical plan, or scheduled for a core biopsy of a node that is clinically suspicious, or have already had a lymph node biopsy and are willing to have a second core biopsy;
* A female subject who is not pregnant or breastfeeding,
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Subjects will be excluded from the study if 1 or more of the following criterion are applicable:
* Contraindications to the use of any aid in detecting nodes during surgery including other magnetic localisation systems or 99mTc-based diagnostic agents for those subjects scheduled for a SLNB and/or ALND;
* Known hypersensitivity to iron oxide or polyethylene glycol compounds;
* For those subjects scheduled for a SLNB and/or ALND, contraindications to the use of 99mTc diagnostic agents;
*Prior history of iron overload disease;
* Known clinical or radiological evidence of distant metastases (Stage IV disease);
* Known inflammatory breast cancer;
* Prior surgical axillary procedure including SLNB or ALND on the ipsilateral side of the breast cancer primary;
* Prior history of breast cancer;
* History of lymphoma with breast or axillary node involvement;
* Previous radiation to the ipsilateral breast or axilla;
* Known metal implant in the ipsilateral axilla or in the ipsilateral chest;
* Any contraindications to MRI imaging;
* Any implant anywhere in the body that produces a magnetic field;
* Recent history of ferumoxytol therapy in the past 6 months;
* Subject received an investigational agent (treatment or diagnostic) within 30 days prior to the surgery;
* Clinically significant acute illness within 4 weeks or other illness deemed to be significant by investigator with agreement of sponsor within 5 days before Day 1;
* Subject, in the opinion of the investigator, should not participate in the study.

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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The intent of the protocol is to have a minimum of 10 subjects overall, with at least 5 subjects that each have at least 1 lymph node positive for HER2 tumor by pathology results. This is an empirically derived number based on a balance of how many positive nodes will be required to estimate the effectiveness of the MSH2TR and detection by MRX measurements at a single dose level. If the investigator(s) can enroll subjects who have a likelihood of having HER2-positive tumor in lymph nodes based on clinical history and findings, then up to 30 subjects will be sufficient.

In general, data will be summarized using descriptive statistics (mean, median, standard deviation, minimum and maximum) or frequency counts and percentages, as appropriate to the type of data. Baseline will be defined as the last available, valid, non-missing assessment prior to dosing.
Only data from protocol scheduled visits/time points will be included in the summary tables. Data from unscheduled visits/time points will not be included in the summary tables but will be included in the figures and listings.
The MRX magnetic moments of each node will be determined and compared to the HER2 designation (HER2 negative; 1+, 2+, or 3+ positive) determined by Standard of Care (SOC) and research pathology tests. Magnetic moments will be calculated using available MRX algorithms.
MRI analysis will include imaging features such as: volume, longest diameter, compactness, irregularity and signal intensity change.
Adverse event data will be summarized by frequency tables. For the safety endpoint, per-treated analysis will be used to include any subject who received the treatment regardless of the eligibility or dose of the treatment received.
Descriptive statistics will be used to summarize the secondary endpoints of the study. Logistic regression models and/or linear regression models will be used to assess the association of the above-mentioned variables with subject’s characteristics in multivariate setting. Other statistical methods, when appropriate, may be used for analysis.
Comparative statistics will be used to generate hypotheses to be tested in subsequent studies. No hypothesis testing is planned.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/03/2021
Actual
24/05/2021
Date of last participant enrolment
Anticipated
31/05/2022
Actual
Date of last data collection
Anticipated
1/06/2022
Actual
Sample size
Target
30
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 17961 0
Monash Medical Centre - Moorabbin campus - East Bentleigh
Recruitment hospital [2] 17962 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [3] 21009 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [4] 21245 0
Lake Macquarie Private Hospital - Gateshead
Recruitment postcode(s) [1] 36118 0
2290 - Gateshead
Recruitment postcode(s) [2] 31836 0
3084 - Heidelberg
Recruitment postcode(s) [3] 31835 0
3165 - East Bentleigh
Recruitment postcode(s) [4] 35842 0
4029 - Royal Brisbane Hospital

Funding & Sponsors
Funding source category [1] 307085 0
Commercial sector/Industry
Name [1] 307085 0
Imagion Biosystems, Ltd
Country [1] 307085 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Imagion Biosystems, Ltd
Address
Level 25, 525 Collins Street
Melbourne, VIC 3000
Country
Australia
Secondary sponsor category [1] 307734 0
None
Name [1] 307734 0
Address [1] 307734 0
Country [1] 307734 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307203 0
St. Vincent's Hospital Melbourne Human Research Ethics Committee
Ethics committee address [1] 307203 0
41 Victoria Parade
Fitzroy VIC 3065
Ethics committee country [1] 307203 0
Australia
Date submitted for ethics approval [1] 307203 0
Approval date [1] 307203 0
06/10/2020
Ethics approval number [1] 307203 0

Summary
Brief summary
This study will assess the safety and effectiveness of an investigational agent (MSH2TR) used to detect lymph node spread of cancer in patients with a specific type of breast cancer, HER2-positive breast cancer.

Who is it for?
You may be eligible for this study if you are a female aged 18 or older, you have histologically confirmed HER2-positive primary breast cancer which you haven't had any prior treatment for (including surgery, radiotherapy, or systemic treatment) and you are scheduled for surgical intervention with lymph node detection by a specific diagnostic agent injection procedure being part of the surgical plan, or scheduled for a core biopsy of a lymph node that is clinically suspicious.

Study details
All enrolled participants will receive a subareolar (the pigmented area around the nipple) injection of the investigational agent after a baseline magnetic resonance imaging (MRI) scan on Day 1. The scan will last approximately 45 minutes. Participants will return for another MRI in 24 hours (Day 2) and on Day 4 to detect the lymph node spread. Also on Day 4, participants will have a tissue sample (biopsy) taken from a cancerous lymph nodes for further examination. The biopsy will be investigated for standard of care as well as a new imaging technique called magnetic relaxometry (MRX). As this study is investigating the safety of the investigational agent, participants will be asked to attend a series of seven (7) clinic visits where they will provide up to three (3) blood and urine samples.

It is hoped this research will demonstrate that a single dose of MSH2TR is safe and well tolerated. It is also hoped that MSH2TR is an effective method for detecting HER-2 positive breast cancer that has spread to lymph nodes using MRI and MRX.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 106394 0
Miss Jane Fox
Address 106394 0
823-865 Centre Road,
Monash Medical Centre- Moorabbin Campus
Bentleigh VIC 3165
Country 106394 0
Australia
Phone 106394 0
+61 03 9575 5100
Fax 106394 0
Email 106394 0
jane.fox@monash.edu
Contact person for public queries
Name 106395 0
Mr Geoff Hollis
Address 106395 0
Imagion Biosystems Limited,
Level 25, 525 Collins St
Melbourne, VIC, 3000
Australia
Country 106395 0
Australia
Phone 106395 0
+61438168008
Fax 106395 0
Email 106395 0
geoff.hollis@imagionbio.com
Contact person for scientific queries
Name 106396 0
Ms Leanne Daly
Address 106396 0
Imagion BioSystems
Level 25 / 525 Collins Street
Victoria 3000
Melbourne
Country 106396 0
Australia
Phone 106396 0
+61418570917
Fax 106396 0
Email 106396 0
leanne.daly@imagionbio.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
As this is an early exploratory study, individual participant data will not be shared.


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.