Evaluation of a Novel Axillary Lymph Node Ink Localization Technique: A Feasibility Study

Patients with breast cancer and metastatic axillary lymphadenopathy routinely undergo neo-adjuvant chemotherapy. For these patients, biopsy clip markers are inserted into the biopsy proven metastatic lymph node pre-treatment, as they may reach complete clinical response post-therapy. Limited axillary surgery, as opposed to a full axillary dissection, may then be indicated. It is still necessary to surgically excise the biopsy proven metastatic lymph node to accurately assess the pathologic response to therapy, and subsequently tailor post-surgical therapies appropriately. As such, these lymph nodes require pre-operative localization which, at The Ottawa Hospital, currently requires radioactive seed insertion under sonographic guidance, typically performed within 5 days of surgery. The procedure is often challenging, as both normal appearing lymph nodes and 3 mm biopsy clip markers are difficult and in some cases impossible, to visualize on ultrasound. At the time of surgery, the excised lymph node is radiographed, to ensure the radioactive seed and biopsy clip marker are both successfully excised. Localization with Ink has the potential to replace both the biopsy clip markers and radioactive seeds as the surgeons are able to directly visualize the Ink intra-operatively and excise the Inked lymph node. A preliminary study out of Stanford on 28 patients who underwent localization of axillary lymph nodes with Ink injected 1-211 days pre-operatively, in the pre neo-adjuvant and post neo-adjuvant settings, showed that lymph nodes injected with Ink are visible intra-operatively months after surgery, suggesting that this is a feasible localization technique (1).

Study Overview

• Status: Withdrawn
• Conditions: Breast Cancer; Axillary Lymphadenitis
• Intervention / Treatment: Device: Black-Eye Ink

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1Y1J7
      • The Ottawa Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• English or French speaking female patients, with a personal history of current pathologically proven breast cancer, over the age of 18 years [patients <18 would be considered a rare occurrence]
• Patients who will be undergoing neoadjuvant chemotherapy
• Patients who will be undergoing axillary lymph node radioactive seed localization
• Patients who will be undergoing axillary surgery

Exclusion Criteria:

• Allergic reaction to Black Eye Ink or any of its components
• Pregnancy
• Confirmed metastatic disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ink placed before chemotherapy (Study A); In Study A, 0.5 mL of Black Eye Ink will be placed in the metastatic LN after neoadjuvant therapy	Device: Black-Eye Ink; There are two proposed studies utilizing the Ink during differing timepoints.Both will identify patients with breast cancer, with a biopsied metastatic axillary lymph node(LN) with a tissue marker clip placed, as is current practice. In Study A, 0.5mL of Black Eye Ink will be placed in the metastatic LN after neoadjuvant therapy. In Study B, 0.5mL of Black Eye Ink will be placed before neoadjuvant therapy. In both studies, the LN containing the tissue marker clip will be the one to have the radioactive seed and Ink inserted. The seed will still be inserted, in the event the dye is not well-visualized. In both studies, the surgeon will attempt to find the LN by direct visualization and then confirm the appropriate LN has been removed by using the Gamma probe and intra-operative radiographs. If the seed is not within the tattooed node, the LN containing the seed will also be removed. All lymph nodes injected with Ink will be removed by the surgeon;no Ink-injected node remains in body.
Active Comparator: Ink placed after chemotherapy (Study B); In Study B, 0.5 mL of Black Eye Ink will be placed before neoadjuvant therapy	Device: Black-Eye Ink; There are two proposed studies utilizing the Ink during differing timepoints.Both will identify patients with breast cancer, with a biopsied metastatic axillary lymph node(LN) with a tissue marker clip placed, as is current practice. In Study A, 0.5mL of Black Eye Ink will be placed in the metastatic LN after neoadjuvant therapy. In Study B, 0.5mL of Black Eye Ink will be placed before neoadjuvant therapy. In both studies, the LN containing the tissue marker clip will be the one to have the radioactive seed and Ink inserted. The seed will still be inserted, in the event the dye is not well-visualized. In both studies, the surgeon will attempt to find the LN by direct visualization and then confirm the appropriate LN has been removed by using the Gamma probe and intra-operative radiographs. If the seed is not within the tattooed node, the LN containing the seed will also be removed. All lymph nodes injected with Ink will be removed by the surgeon;no Ink-injected node remains in body.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Identification rate of Inked nodes, containing seed and clip	3 years
Identification rate of Inked nodes, not containing seed	3 years
Identification rate of Inked nodes, not containing clip	3 years
Identification rate of Inked nodes, not containing seed or clip	3 years

Collaborators and Investigators

• Sponsor: The Ottawa Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2020
• Primary Completion (Actual): June 19, 2023
• Study Completion (Actual): June 19, 2023

Study Registration Dates

• First Submitted: October 2, 2019
• First Submitted That Met QC Criteria: October 22, 2019
• First Posted (Actual): October 23, 2019

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Lymphatic Diseases; Lymphadenitis
• Other Study ID Numbers: 20180569-01H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Only study staff will have access to the study data. Only de-identified data will be collected in all study documents. The OHSN-REB and OHRI may review original patient medical records and relevant study records under the supervision of the investigator for audit purposes.

Drug and device information, study documents

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