Comparison of Use of Indocyanine Green and 99mTc-labeled Radiotracer for Axillary Lymphatic Mapping in Patients With Breast Cancer

This clinical trial will enroll up to 130 adult women with a confirmed diagnosis of clinical stage 1 or 2 breast cancer who are undergoing breast cancer surgery with lumpectomy or mastectomy and planned axillary sentinel node biopsy procedure. Participants will undergo lymphatic mapping with technetium Tc-99m (99mTc) sulfur colloid in accordance with routine clinical practice. Injections of 99mTc sulfur colloid will take place the afternoon prior to planned next morning surgery or on the morning of surgery. Participants will undergo lymphoscintigraphy in accordance with standard clinical practice.

Immediately prior to operation, after the induction of anesthesia in the operating room, up to 1cc of 0.5% indocyanine green (ICG) solution will be injected subdermally close to the tumor or into the subareolar region after disinfection of the breast skin. ICG movement will be facilitated by manual massage and monitored with fluorescence imaging. ICG fluorescence will be elicited and detected by Photodynamic Eye (PDE) camera. The lymphatic drainage, made evident by the fluorescent dye, will be monitored in real time on a monitor. The fluorescence will be followed towards the armpit region (axilla) and time for the fluorescence to reach the axilla will be recorded. Following standard practice, an incision will be made in the armpit region. Fluorescent lymph nodes (ICG positive) will be localized and removed and analyzed by a pathologist. Node removal will continue until no residual fluorescence is visible in the axilla. Removed nodes will be tested for radioactivity using a standard gamma-detecting probe and the counts per minute will be recorded. Finally, the armpit region will be inspected with the gamma probe to determine if there are any residual radioactive nodes. Residual sentinel nodes (the first node to receive lymph from a tumor) will be removed. For the purposes of this study, the sentinel status of a node will be defined as being flagged as sentinel by either one or both of the ICG or 99mTc methods. The goal of the project is to confirm that axillary lymphatic mapping with ICG leads to similar nodes being labeled as sentinel as lymphatic mapping with 99mTc-labeled radiotracer.

Study Overview

• Status: Completed
• Conditions: Stage I Breast Cancer; Stage II Breast Cancer
• Intervention / Treatment: Drug: Indocyanine Green Solution; Radiation: Technetium Tc-99m Sulfur Colloid; Procedure: Lymphoscintigraphy; Procedure: Axillary Lymph Node Biopsy

Detailed Description

PRIMARY OBJECTIVES:

I. To confirm that axillary lymphatic mapping with indocyanine green solution (ICG) solution leads to a similar number of nodes being labeled as sentinel as lymphatic mapping with 99mTc-labeled (technetium Tc-99m sulfur colloid) radiotracer.

OUTLINE:

Participants receive technetium Tc-99m sulfur colloid injection and undergo lymphoscintigraphy according to clinical practice. Prior to surgery, participants also receive indocyanine green solution subdermally close to the tumor or into subareolar region of the breast skin. Participants then undergo axillary sentinel node biopsy and surgery.

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Instititute, Case Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Participants with a confirmed diagnosis of clinical stage 1 or 2 breast cancer
• Participants who are undergoing breast cancer surgery with lumpectomy or mastectomy
• Participants with planned axillary sentinel node biopsy procedure

Exclusion Criteria:

• Participants with cancer > 3 cm
• Participants with clinically positive nodes
• Participants with prior surgery for breast cancer in the index breast
• Participants who have had bilateral breast surgeries
• Thyroid dysfunction
• Hypersensitivity to iodine
• Hepatic insufficiency
• Renal insufficiency

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Diagnostic (indocyanine green, 99mTc-labeled radiotracer); Participants receive technetium Tc-99m sulfur colloid injection and undergo lymphoscintigraphy according to clinical practice. Prior to surgery, participants also receive indocyanine green solution subdermally close to the tumor or into subareolar region of the breast skin. Participants then undergo Axillary Lymph Node Biopsy and surgery.

Drug: Indocyanine Green Solution; Given subdermally; Other Names: IC-GREEN; ICG solution; Radiation: Technetium Tc-99m Sulfur Colloid; Given via injection; Other Names: Tc 99m Sulfur Colloid; Tc-99m SC; Technetium Tc 99m Sulfur Colloid; Procedure: Lymphoscintigraphy; This is a method used to check the lymph system for disease. A radioactive substance that flows through the lymph ducts and can be taken up by lymph nodes is injected into the body. A scanner or probe is used to follow the movement of this substance on a computer screen. Lymphoscintigraphy is used to find the sentinel lymph node (the first node to receive lymph from a tumor), which may be removed and checked for tumor cells. Lymphoscintigraphy is also used to diagnose certain diseases or conditions, such as lymphoma or lymphedema.; Other Names: Undergo lymphoscintigraphy; Procedure: Axillary Lymph Node Biopsy; Undergo biopsy; Other Names: Axillary Node Biopsy; axillary sentinel lymph node biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Sentinel Lymph Nodes (SLNs) Flagged by the Two Methods	Let A be the number of Tc-positive and ICG-positive sentinel nodes (SNs) detected, B be the number of Tc-positive and ICG-negative SNs detected, and C be the number of Tc-negative and ICG-positive SNs detected. The total number (N) of SNs detected is therefore N = (A + B + C); the proportion of SNs detected by the Tc method (PTc) is (A + B)/N; and the proportion of SNs detected by the ICG method (PICG) is (A + C)/N. Differences in the proportions of SLNs flagged will be compared using a two-sided 95% confidence interval.	Baseline

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI); Mitaka USA, Inc.
• Investigators: Principal Investigator: Stephen Grobmyer, MD, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 17, 2015
• Primary Completion (ACTUAL): February 1, 2019
• Study Completion (ACTUAL): February 1, 2019

Study Registration Dates

• First Submitted: April 14, 2015
• First Submitted That Met QC Criteria: April 16, 2015
• First Posted (ESTIMATE): April 17, 2015

Study Record Updates

• Last Update Posted (ACTUAL): June 30, 2022
• Last Update Submitted That Met QC Criteria: June 29, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Mastectomy, Segmental; Indocyanine Green; Sentinel Lymph Node Biopsy; Lumpectomy; Near Infrared Fluorescence Imaging; axillary lymph node mapping
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Pharmaceutical Solutions; Technetium Tc 99m Sulfur Colloid
• Other Study ID Numbers: CASE10114

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No