ANZCTR - Registration

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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

16/11/2023

Date data sharing statement initially provided

5/08/2021

Type of registration

Prospectively registered

Titles & IDs

Public title

New tracer compared with traditional radioactive tracer for sentinel lymph node biopsy in breast cancer: The FLUORO trial

Scientific title

Indocyanine green compared with technetium-99m for sentinel lymph node biopsy in early breast cancer: The FLUORO trial

Secondary ID [1]

None

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

breast cancer

Condition category

Condition code

Surgery

Surgical techniques

Cancer

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]

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]

Number of sentinel lymph nodes identified using indocyanine green (ICG) only. This will be determined from the surgeon and the operation report.

Timepoint [1]

Intraoperative

Primary outcome [2]

Number of sentinel lymph nodes identified using technetium-99m (99mTc) only. This will be determined from the surgeon and the operation report.

Timepoint [2]

Intraoperative

Primary outcome [3]

Number of sentinel lymph nodes identified using both ICG and 99mTc. This will be determined from the surgeon and the operation report.

Timepoint [3]

Intraoperative

Secondary outcome [1]

Surgeon’s reported ease of identifying sentinel lymph nodes with ICG to 99mTc according to a Likert scale

Timepoint [1]

Intraoperative

Secondary outcome [2]

Any wound-related complications

Timepoint [2]

30 days postoperative from planned followup visits and any hospital records from any presentations

Secondary outcome [3]

Hospital admission duration

Timepoint [3]

30 days postoperative from any hospital records from any presentations

Secondary outcome [4]

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]

30 days postoperative from planned followup visits

Secondary outcome [5]

Number of pathologically positive nodes identified using indocyanine green (ICG) only. This will be determined from the histopathology report.

Timepoint [5]

Intraoperative

Secondary outcome [6]

Number of pathologically positive nodes identified using technetium-99m (99mTc) only. This will be determined from the histopathology report.

Timepoint [6]

Intraoperative

Secondary outcome [7]

Number of pathologically positive nodes identified using both ICG and 99mTc. This will be determined from the histopathology report.

Timepoint [7]

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

Sex

Females

Can healthy volunteers participate?

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

29/08/2021

Date of last participant enrolment

Anticipated

1/01/2025

Actual

Date of last data collection

Anticipated

1/04/2025

Actual

Sample size

Target

290

Accrual to date

204

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

The Chris O’Brien Lifehouse - Camperdown

Recruitment postcode(s) [1]

2050 - Camperdown

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Chris O'Brien Lifehouse

Address [1]

119-143 Missenden Rd, Camperdown NSW 2050

Country [1]

Australia

Primary sponsor type

Hospital

Name

Chris O'Brien Lifehouse

Address

119-143 Missenden Rd, Camperdown NSW 2050

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

SLHD RPA - Research Ethics and Governance Office

Ethics committee address [1]

50 Missenden Rd, Camperdown NSW 2050

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

21/05/2021

Approval date [1]

29/06/2021

Ethics approval number [1]

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

A/Prof Sanjay Warrier

Address

Chris O'Brien Lifehouse, 119-143 Missenden Rd, Camperdown NSW 2050

Country

Australia

Phone

+61 412130660

Fax

Sanjay@drsanjaywarrier.com.au

Contact person for public queries

Name

Chu Luan Nguyen

Address

Chris O'Brien Lifehouse, 119-143 Missenden Rd, Camperdown NSW 2050

Country

Australia

Phone

+61 401608581

Fax

chuluannguyen@gmail.com

Contact person for scientific queries

Name

Chu Luan Nguyen

Address

Chris O'Brien Lifehouse, 119-143 Missenden Rd, Camperdown NSW 2050

Country

Australia

Phone

+61 401608581

Fax

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?

Doc. No.	Type	Email	Attachment
11733	Study protocol	chuluannguyen@gmail.com	382041-(Uploaded-24-06-2021-23-30-47)-Study-related document.docx
11734	Informed consent form	chuluannguyen@gmail.com	382041-(Uploaded-24-06-2021-23-31-39)-Study-related document.doc
12264	Informed consent form		382041-(Uploaded-24-06-2021-23-31-39)-Study-related document.docx

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Novel Dual Tracer Indocyanine Green and Radioisotope Versus Gold Standard Sentinel Lymph Node Biopsy in Breast Cancer: The GREENORBLUE Trial.	2023	https://dx.doi.org/10.1245/s10434-023-13824-6

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added automatically