Sentinel lympH Node Biopsy With Indocyanine Green in Breast Cancer After NEoadjuvant Chemotherapy (SHINE) (SHINE)

Sentinel lympH Node Biopsy With Indocyanine Green in Breast Cancer After NEoadjuvant Chemotherapy (SHINE): A Prospective Clinical Trial

This is a prospective, open-label, within-patient clinical trial to determine the accuracy of Indocyanine green (ICG) guided sentinel lymph node biopsy (SLNB) compared to the standard dual-tracer SLNB in breast cancer patients who have had chemotherapy as a first treatment using a non-inferiority design.

Patients with operable breast cancer treated with chemotherapy and eligible for SLNB will be included in the study. During surgery, ICG will be injected and used to identify fluorescent sentinel nodes using a hand-held imaging camera; radiotracer and blue dye will also be used as per standard protocols. Intraoperative and clinicopathologic outcomes such as complications, characteristics of nodes, false negative rates and feasibility will be assessed. Patients will be asked to complete standardized patient reported outcome questionnaires (Breast-Q, FACT-B+4, VAS) to define the patient experience with this novel technique.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Procedure: ICG guided sentinel lymph node biopsy

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tulin Cil, MD MSc FRCSC; Phone Number: 3984 416-946-4501; Email: tulin.cil@uhn.ca
• Study Contact Backup: Name: Karineh Kazazian, MD PhD FRCSC; Phone Number: 4163403444; Email: karineh.kazazian2@uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G2M9
      • Recruiting
      • University Health Network
      • Contact: Tulin Cil, MD, MEd; Phone Number: 4169464507; Email: tulin.cil@uhn.ca
      • Contact: Emma Reel, MSW; Phone Number: 6472021028; Email: emma.reel@uhn.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adults ≥ 18 and ≤ 80
2. Stage I-III core biopsy confirmed invasive breast cancer, who have undergone neoadjuvant chemotherapy and are planned to undergo SLNB with dual tracer (blue dye+Tc-99m)
3. Eastern Cooperative Oncology Group (ECOG) < 2
4. No ICG/iodine allergy
5. Capable of providing informed consent
6. English literacy

Exclusion Criteria:

1. Significant medical comorbidities (ASA 4)
2. Breast cancer stage T4/inflammatory or N2 disease at presentation (SLNB is contra-indicated in this setting)
3. Clinical node positive after neoadjuvant therapy (SLNB is contra-indicated in this setting)
4. Previous axillary surgery or breast/axillary radiotherapy to ipsilateral breast
5. Active pregnancy or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ICG-SLNB; This is a prospective within-patient clinical study to assess the accuracy of ICG SLNB compared to standard dual-tracer SLNB in breast cancer patients treated with neoadjuvant chemotherapy. For SLNB, triple localization of the sentinel lymph nodes using blue dye, Tc-99m and ICG will be utilized in each patient.

Procedure: ICG guided sentinel lymph node biopsy; During sentinel lymph node biopsy the surgeon will inject a volume of 0.1ml divided into 2 doses (0.05ml each) of 2.5mg/mL ICG into the periareolar dermis of the involved breast. Technetium and blue dye will also be administered as per standard of care. The surgeon will assess the axilla with the the SPY-PHI near infrared imaging system to identify and remove ICG-fluorescent nodes; Any other sentinel lymph nodes identified will also be removed as per standard of care. If there is no progression of ICG towards the axilla, or if no ICG sentinel lymph node can be identified, an alternate injection technique involving peritumoural injection at 2-3 locations near the cancer site in the subcutaneous or dermal space of 0.05ml will be utilized.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-inferiority of ICG SLNB compared to dual-tracer SLNB in post-neoadjuvant chemotherapy treated breast cancer patients.	Proportion of lymph nodes identified with ICG compared to the proportion of lymph nodes identified with dual tracer (blue dye/Tc-99m gamma probe)	From Technetium-99 (Tc-99m) injection to the completion of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complications/safety	Surgical intra-operative and post-operative complications will be collected to determine safety outcomes. All intra-operative complications will be graded using the ClassIntra classification. All post-operative complications (up to 30 days post-surgical treatment) will be graded using the Clavien-Dindo classification. Treatment-related adverse events will be assessed by CTCAE v5.0.	From time of Technetium-99 (Tc-99m) injection to 30 days after surgery
Patient reported outcome measures - Visual Analog Scale	Patients' self-report the intensity of their pain. Scale 0-10, where 10 indicated worst pain possible.	From baseline/enrolment to 12 months from surgery
Patient reported outcome measures - FACT-B+4	Breast cancer patients' self-report on various dimensions of their Quality of Life: Measures physical well-being (score range 0-28; higher score = worse outcome), social/family well-being (score range 0-28; higher score = better outcome), emotional well-being (score range 0-24; higher score = worse outcome), functional well-being (score range 0-28; higher score = better outcome), breast cancer subscale (score range 0-28; higher score = worse outcome), lymphedema subscale (score range 0-20; higher score = worse outcome).	From baseline/enrolment to 12 months from surgery
Patient reported outcome measures - Breast-Q	Breast cancer patients' self-report their perceptions of domains of Quality of Life. Scale 0-100; 100 indicates better satisfaction.	From baseline/enrolment to 12 months from surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Budget impact analysis	We will quantify all direct costs associated with implementation of ICG guided SLNB in breast cancer and annual operational costs; these will enable a comparison to cost of the current standard SLNB with Tc-99m and blue dye, including nuclear medicine infrastructure, technicians, and additional health care visits.	1 year

Collaborators and Investigators

• Sponsor: University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Estimated): March 31, 2024
• Primary Completion (Estimated): April 30, 2025
• Study Completion (Estimated): April 30, 2026

Study Registration Dates

• First Submitted: October 1, 2023
• First Submitted That Met QC Criteria: October 13, 2023
• First Posted (Actual): October 16, 2023

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Neoadjuvant chemotherapy; Indocyanine green; Sentinel lymph node biopsy; Invasive breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 20-6215.0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No