Sentinel Lymph Node Biopsy Findings in Patients With Breast Cancer

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Lymphoseek
* Drug: Sulfur Colloid


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lymphoseek<br>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<br>* 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.<br>* Other names: technetium Tc 99m tilmanocept;|
| Active Comparator: Sulfur Colloid<br>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<br>* 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.<br>* Other names: 99mTc-SC Sulfur Colloid;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sentinel Node