Sentinel Lymph Node Biopsy Findings in Patients With Breast Cancer (Lymphoseek)

A Randomized, Double-Blinded Trial Comparing Lymphoseek and 99mTc-Sulfur Colloid With Regard to Pre-op Imaging and Imaging Drug Kinetics and Intra-op Lymphatic Mapping and Sentinel Lymph Node Biopsy Findings in Patients With Breast Cancer

To compare the kinetics and efficacy of two functionally different diagnostic agents, Lymphoseek (CD206 receptor targeted) and 99mTc-Sulfur Colloid (SC) (Sulfur Colloid non-specific mapping agent) in intraoperative lymphatic mapping (ILM) and Sentinel Lymph Node Biopsy (SLNB).

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Lymphoseek; Drug: Sulfur Colloid

Detailed Description

Single center, blinded, randomized, parallel-group, comparative study of Lymphoseek and 99mTc-SC in the preoperative and intraoperative detection of lymph nodes in subjects with known breast cancer. All subjects will receive a single dose of 50 μg Lymphoseek radiolabeled with 0.5 millicurie (mCi) Tc 99m or 0.5 mCi of 99mTc-SC. Subjects may also receive up to 1 mL of vital blue dye (VBD) as a companion ILM agent. All radio-labeled agents will be administered in a single intradermal injection.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• The subject must be female and 18 years of age or older.
• The subject must be a preoperative clinical Tis, T1, T2, T3, T4, as well as clinical N0 and clinical M0 breast cancer
• The subject must have a diagnosis of primary breast cancer.
• The subject must be a candidate for surgical intervention, either with lumpectomy and SLNB or with mastectomy and SLNB, as the treatment of her breast cancer.
• The subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of Grade 0 - 2
• The subject must provide written informed consent with Health Insurance Portability and Accountability Act (HIPAA) authorization before participating in the study

Exclusion Criteria:

• The subject has clinical or radiological or pathologic evidence of metastatic cancer, including any abnormal or enlarged clinical palpable lymph nodes or core biopsy/surgical biopsy/fine-needle-aspiration evidence of malignant cell within any lymph nodes.
• The subject has a known hypersensitivity to vital blue dye (VBD) in a case where vital blue dye was planned for use during SLNB.
• The subject has a positive pregnancy test or is lactating.
• The subject has had prior surgery to the indicated breast or axilla.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Lymphoseek; Lymphoseek (technetium Tc 99m tilmanocept) Injection is indicated for lymphatic mapping with a hand-held gamma counter to assist in the localization of lymph nodes draining a primary tumor site in patients with breast cancer or melanoma and guiding sentinel lymph node biopsy using a hand-held gamma counter in patients with clinically node negative squamous cell carcinoma of the oral cavity.	Drug: Lymphoseek; Subjects will receive a single intradermal injection of Lymphoseek followed by SPECT imaging conducted in two phases: initial sequential planar imaging at 30 to 60 second intervals for the first 60 minutes and repeated at 90 minutes and 120 minutes, as indicated, for identification of the SLN followed by SPECT/CT for higher resolution imaging in transaxial, coronal, and sagittal planes. Subjects will then proceed to surgery for lymphatic mapping. Lymphoseek positivity will be based upon radioactivity counts derived from the application of the handheld gamma probe ex vivo. Tumor resection or mastectomy will be performed according to standard procedures.; Other Names: technetium Tc 99m tilmanocept
Active Comparator: Sulfur Colloid; Technetium Tc 99m Sulfur Colloid Injection is a radioactive diagnostic agent indicated for use as follows: In adults, to assist in the: localization of lymph nodes draining a primary tumor in patients with; breast cancer or malignant melanoma when used with a hand-held gamma counter.; evaluation of peritoneovenous (LeVeen) shunt patency in adults.	Drug: Sulfur Colloid; Subjects will receive a single intradermal injection of 99mTc-SC followed by SPECT imaging conducted in two phases: initial sequential planar imaging at 30 to 60 second intervals for the first 60 minutes and repeated at 90 minutes and 120 minutes, as indicated, for identification of the SLN followed by SPECT/CT for higher resolution imaging in transaxial, coronal, and sagittal planes. Subjects will then proceed to surgery for lymphatic mapping. 99mTc-SC positivity will be based upon radioactivity counts derived from the application of the handheld gamma probe ex vivo. Tumor resection or mastectomy will be performed according to standard procedures.; Other Names: 99mTc-SC; 99mTc-SC Sulfur Colloid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Injection Site Clearance for Lymphoseek and 99mTc-Sulfur Colloid (SC).	The rate of injection site clearance is the time from radiotracer injection to peak SLN radioactive level. Injection clearance rates will be determined by planar SPECT imaging and by SPECT/CT. Subjects will undergo standard sequential planar imaging at 30 to 60 seconds intervals until the sentinel lymph node is seen. Once a sentinel node is located, a SPECT/CT will be performed for higher resolution imaging in transaxial, coronal, and sagittal planes.	2 hours
Sentinel Lymph Node Uptake Rate	SLN uptake rates will be determined by planar SPECT (single-photon emission computerized tomography) imaging and by SPECT/CT (CT-computed tomography). Gamma counts will be obtained at the injection site by standard sequential planar imaging at 30 to 60 seconds intervals until the sentinel lymph node is seen. Once a sentinel node is located, a SPECT/CT will be performed for higher resolution imaging in transaxial, coronal, and sagittal planes. Figures showing the percent of peak activity in the node versus time will be constructed for each radiopharmaceutical. The average uptake rate for each radiopharmaceutical will be computed and the following test will be conducted using a two-sample t-test at a two-sided α=0.05 (one-sided α=0.025) level of significance: H0 (null hypothesis): µLS ≤ µSC vs. HA (alternative hypothesis): µLS > µSC, (µLS is the average SLN uptake rate of Lymphoseek) (µSC is the average SLN uptake rate of 99mTc Sulfur Colloid).	2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Intraoperatively Detected Sentinel Lymph Nodes (SLNs) Identified	To compare the number of intraoperatively detected SLNs identified by Lymphoseek and 99mTc-SC on an agent cohort basis	24 hours
Ratio of Intraoperative Gamma Counts	To compare differences in the ratio of intraoperative counts for Lymphoseek vs 99mTc-SC for the hottest harvested axillary Sentinel Lymph Node (SLN) relative to the primary intradermal injection site.	24 hours
Patient Pain Tolerance	To compare patient pain tolerance (i.e., patient's perceived level of discomfort) at the injection site for Lymphoseek vs 99mTc-SC using Wong-Baker pain rating scale of 0-10, where the higher the score, the higher the pain level.	24 hours
Pathologic Assessment of the Excised Lymph Node(s)	To compare pathologic assessment of the excised lymph node(s) to confirm the presence/absence of tumor metastases for Lymphoseek vs 99mTc-SC.	24 hours

Collaborators and Investigators

• Sponsor: Kettering Health Network
• Investigators: Principal Investigator: Arash Kardan, MD, Kettering Health Network

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2015
• Primary Completion (Actual): January 23, 2017
• Study Completion (Actual): August 31, 2017

Study Registration Dates

• First Submitted: November 6, 2014
• First Submitted That Met QC Criteria: November 10, 2014
• First Posted (Estimate): November 11, 2014

Study Record Updates

• Last Update Posted (Actual): July 28, 2020
• Last Update Submitted That Met QC Criteria: July 14, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Sentinel Node
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: KHNIC-P14-N001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No