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Trial registered on ANZCTR


Registration number
ACTRN12621001033831
Ethics application status
Approved
Date submitted
21/05/2021
Date registered
5/08/2021
Date last updated
5/08/2021
Date data sharing statement initially provided
5/08/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
New tracer compared with traditional radioactive tracer for sentinel lymph node biopsy in breast cancer
Scientific title
Indocyanine green compared with technetium-99m for sentinel lymph node biopsy in breast cancer: A prospective trial
Secondary ID [1] 304280 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
breast cancer 322007 0
Condition category
Condition code
Surgery 319728 319728 0 0
Surgical techniques
Cancer 320169 320169 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a non-randomised trial. All participants who have consented to participate will undergo sentinel lymph node biopsy using both indocyanine green and technetium-99mm techniques. At the time of surgery after anaesthesia and immediately before the operation, 0.5 mL of Infracyanine® 25mg/10mL (SERB, Paris, France) will be injected subdermally into the peri-areolar area of the breast. Movement of ICG in the lymph ducts will be facilitated by manual massage.

Operating room lights will be turned off to avoid any potential interference of ambient light with detection of ICG fluorescence. Fluorescence of ICG will be immediately elicited and detected by the near-infrared (NIR) camera (SPY-PHI, Novadaq Technologies Inc., Mississauga, Canada). The lymphatic drainage will be visualized in real time on a monitor. The fluorescence will be followed from the site of injection towards the axilla, and where the fluorescence disappears into the axilla, an incision is made to commence the biopsy.

The fluorescent lymphatic channels will then be dissected and followed to the first ICG avid lymph node with assistance from the NIR camera. The lymphatic channels will be clipped and ligated to avoid ICG leakage into the dissection field which can distort visualisation of lymphatic anatomy. Fluorescent lymph nodes (ICG-positive) will then be localized and excised. These excised ICG-positive nodes will then be tested for radioactivity using a gamma-detecting probe and classified as hot (99mTc-positive) or cold (99mTc-negative). Sentinel lymph node removal will continue until no residual fluorescence is visible in the axilla.

Finally, the axilla will be inspected with the gamma-detecting probe to determine whether any radioactivity is left. If there is significant residual radioactivity the hot spot (considered to be a 99mTc-positive SLN) will be removed and examined. The number of sentinel nodes (ICG-positive, 99mTc-positive, or both) removed from each patient will be documented. With regard to radioactivity, a SLN will be defined as any node that when measured ex vivo will have a gamma count ratio, compared to the background axilla, of 10:1. All SLNs will be sent for histopathology analysis.

Sentinel lymph nodes will be compared to identify concordance among those identified as fluorescent, radioactive, and both. The total number of SLNs identified by ICG, 99mTc, or both, will be recorded.

The approximate duration of the procedure will be 1 hour if it is combined with a wide-local excision. The duration of the procedure will be 1.5 hours if it is combined with a mastectomy.
Intervention code [1] 320618 0
Treatment: Surgery
Comparator / control treatment
Technetium-99m sentinel lymph node mapping and biopsy
Patients eligible for SLNB will undergo standard-of-care preoperative lymphoscintigraphy with subdermal/ peri-tumour injection of 99mTc the day prior to surgery. The day before surgery or on the morning of surgery, 1 periareolar injection of 100 megabecquerel (MBq) will be given and lymphoscintigraphy performed.

The sentinel lymph node biopsy will then proceed as outlined above for the interventional group.
Control group
Active

Outcomes
Primary outcome [1] 327594 0
Number of sentinel lymph nodes identified using indocyanine green (ICG) only. This will be determined from the surgeon and the operation report.
Timepoint [1] 327594 0
Intraoperative
Primary outcome [2] 328051 0
Number of sentinel lymph nodes identified using technetium-99m (99mTc) only. This will be determined from the surgeon and the operation report.
Timepoint [2] 328051 0
Intraoperative
Primary outcome [3] 328052 0
Number of sentinel lymph nodes identified using both ICG and 99mTc. This will be determined from the surgeon and the operation report.
Timepoint [3] 328052 0
Intraoperative
Secondary outcome [1] 395839 0
Surgeon’s reported ease of identifying sentinel lymph nodes with ICG to 99mTc according to a Likert scale
Timepoint [1] 395839 0
Intraoperative
Secondary outcome [2] 397340 0
Any wound-related complications
Timepoint [2] 397340 0
30 days postoperative from planned followup visits and any hospital records from any presentations
Secondary outcome [3] 397341 0
Hospital admission duration
Timepoint [3] 397341 0
30 days postoperative from any hospital records from any presentations
Secondary outcome [4] 397342 0
Need for any axillary treatment such as axillary dissection or adjuvant therapy. This will be determined from the followup visit postoperative and the hospital medical records.
Timepoint [4] 397342 0
30 days postoperative from planned followup visits
Secondary outcome [5] 398914 0
Number of pathologically positive nodes identified using indocyanine green (ICG) only. This will be determined from the histopathology report.
Timepoint [5] 398914 0
Intraoperative
Secondary outcome [6] 398915 0
Number of pathologically positive nodes identified using technetium-99m (99mTc) only. This will be determined from the histopathology report.
Timepoint [6] 398915 0
Intraoperative
Secondary outcome [7] 398916 0
Number of pathologically positive nodes identified using both ICG and 99mTc. This will be determined from the histopathology report.
Timepoint [7] 398916 0
Intraoperative

Eligibility
Key inclusion criteria
- Participant has clinically node-negative early breast cancer undergoing sentinel lymph node biopsy
- Female, age 18 years or older
- Participant understands the study procedures and can provide informed consent to participate in the study
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Participant does not have clinically node-negative early breast cancer (tumour size >3 cm +/- clinically positive lymph nodes)
- Participant has known contraindication to ICG injection, i.e., previous reaction to ICG
- Participant has Iodine allergy
- Participant has chronic kidney disease stage 3, 4, or 5
- Participant is pregnant
- Refusal to consent to participation in the study

Study design
Purpose of the study
Treatment
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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Data will be described using means or medians where appropriate, ranges for continuous variables, and counts and percentages for categorical variables.

Sample size estimates were calculated to evaluate the equivalency of ICG to 99mTc in terms of detection rate of sentinel lymph nodes. They are based on a detection rate with 99mTc of 96.5%. A 5% difference in detection rate was of no clinical significance. Using a true detection rate of 97.9%, at alpha = 0.05, the sample size to yield 80% power is n = 224 sentinel lymph nodes. The mean number of sentinel lymph nodes removed based on the literature was taken as 2.4, equating to at least 93 patients needed for this trial.

The null hypothesis for equivalence of ICG and 99mTc SLN mapping techniques will be the difference between the proportion of SLNs detected by each method that lie outside the margin (-5%, 5%). Tests for equivalence will be based on analysing clustered paired binary data and results presented by a 2-sided 95% confidence interval compared with 5% equivalence region. McNemar test will be used to compare the difference in detection rate between the 2 methods for pathologically positive axillary SLNs. Statistical analysis will be performed with RStudio, version 1.4.1106.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 19515 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment postcode(s) [1] 34111 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 308656 0
Hospital
Name [1] 308656 0
Chris O'Brien Lifehouse
Address [1] 308656 0
119-143 Missenden Rd, Camperdown NSW 2050
Country [1] 308656 0
Australia
Primary sponsor type
Hospital
Name
Chris O'Brien Lifehouse
Address
119-143 Missenden Rd, Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 309535 0
None
Name [1] 309535 0
Address [1] 309535 0
Country [1] 309535 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308582 0
SLHD RPA - Research Ethics and Governance Office
Ethics committee address [1] 308582 0
50 Missenden Rd, Camperdown NSW 2050
Ethics committee country [1] 308582 0
Australia
Date submitted for ethics approval [1] 308582 0
21/05/2021
Approval date [1] 308582 0
29/06/2021
Ethics approval number [1] 308582 0
X21-0156 & 2021/ETH00747

Summary
Brief summary
The aim of this study is to investigate the efficacy of a new tracer called indocyanine green compared to the traditional radioactive tracer technetium-99m in identification and biopsy of sentinel lymph nodes for patients with breast cancer.

Who is it for?
You may be eligible for this study if you are aged 18 years or older, have clinically node-negative early breast cancer, and are scheduled to undergo a sentinel lymph node biopsy.

Study details
Participants will receive sentinel lymph node biopsy with both indocyanine green and technetium-99m techniques. The procedure is anticipated to take up to approximately 60 minutes. After the procedure, all participants will followup in 7 days and 30 days.

It is hoped that this study may demonstrate that use of indocyanine green for sentinel node biopsy is equivalent to technetium-99m, and therefore may provide a safe and effective alternative to use of a radioactive tracer for future breast cancer patients undergoing a sentinel node biopsy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 111222 0
A/Prof Sanjay Warrier
Address 111222 0
Chris O'Brien Lifehouse, 119-143 Missenden Rd, Camperdown NSW 2050
Country 111222 0
Australia
Phone 111222 0
+61 412130660
Fax 111222 0
Email 111222 0
Sanjay@drsanjaywarrier.com.au
Contact person for public queries
Name 111223 0
Dr Chu Luan Nguyen
Address 111223 0
Chris O'Brien Lifehouse, 119-143 Missenden Rd, Camperdown NSW 2050
Country 111223 0
Australia
Phone 111223 0
+61 401608581
Fax 111223 0
Email 111223 0
chuluannguyen@gmail.com
Contact person for scientific queries
Name 111224 0
Dr Chu Luan Nguyen
Address 111224 0
Chris O'Brien Lifehouse, 119-143 Missenden Rd, Camperdown NSW 2050
Country 111224 0
Australia
Phone 111224 0
+61 401608581
Fax 111224 0
Email 111224 0
chuluannguyen@gmail.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified data of all variables collected. Demographic information will be collected including tumour type, previous breast or axilla surgery and obesity. Intraoperative information will be collected including the number of nodes identified with ICG and 99mTc, which technique allowed for first detection of the lymph node, the surgeon’s reported ease of detection with ICG and 99mTc, and operation duration. Postoperative information will be collected including hospital admission duration, complications, the number of pathologically positive lymph nodes on histopathology, the need for any axillary treatment (none, radiotherapy or axillary dissection), and followup visit information at 7 and 30 days postoperative.
When will data be available (start and end dates)?
November 2021 to November 2036.
Available to whom?
Other researchers or clinicians who are interested.
Available for what types of analyses?
For verification of results or setup of a similar study.
How or where can data be obtained?
An email request can be sent to the investigator, Dr Chu Nguyen, who will discuss this with the Cheif investigator, A/Prof Sanjay Warrier. If approved, the electronic data spreadsheet will be emailed to the person interested. Email: chuluannguyen@gmail.com
What supporting documents are/will be available?
Study protocol
Informed consent form
How or where can supporting documents be obtained?
Type [1] 11733 0
Study protocol
Citation [1] 11733 0
Link [1] 11733 0
Email [1] 11733 0
chuluannguyen@gmail.com
Other [1] 11733 0
Type [2] 11734 0
Informed consent form
Citation [2] 11734 0
Link [2] 11734 0
Email [2] 11734 0
chuluannguyen@gmail.com
Other [2] 11734 0
Type [3] 12264 0
Informed consent form
Citation [3] 12264 0
Link [3] 12264 0
Email [3] 12264 0
Other [3] 12264 0
Summary results
No Results