Intravital Microscopy in Identifying Tumor Vessels in Patients With Stage IB-IIIC Melanoma Undergoing Sentinel Lymph Node Biopsy

Study Overview
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Brief Summary
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This pilot clinical trial studies intravital microscopy in identifying tumor vessels in patients with stage IB-IIIC melanoma undergoing sentinel lymph node biopsy. By examining sentinel lymph nodes through intravital microscopy before they are removed, doctors may learn specific information regarding how melanoma may spread to lymph nodes and other sites of the body.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the feasibility of intravital microscopy in characterizing the microvasculature of the sentinel lymph node (SLN) in melanoma patients requiring SLN biopsy. SECONDARY OBJECTIVES: I. To identify vascular blood flow parameters and flow kinetics associated with the sentinel lymph node vasculature and define the utility of using commonly used fluorescent agents during human intravital microscopy and correlate with clinical outcomes (time to recurrence, survival), as a potential basis for a novel prognostic tool and/or microstaging technique. TERTIARY OBJECTIVES: I. To determine the relationship between live microscopically-recorded images and pathology slides in terms of vessel density and vessel diameter. OUTLINE: Patients receive indocyanine green and fluorescein sodium injection intravenously (IV) and then undergo intravital microscopic observation over 15-20 minutes during standard of care sentinel node biopsy. After completion of study treatment, patients are followed up at 3 weeks and then every 6 months for 5 years or every 3 months for 2 years and every 6 months for another 2 years.

Official Title
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Intravital Microscopy (IVM) During Sentinel Lymph Node (SLN) Biopsy for Melanoma

Conditions
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Stage IB Skin Melanoma, Stage IIA Skin Melanoma, Stage IIB Skin Melanoma, Stage IIC Skin Melanoma, Stage IIIA Skin Melanoma, Stage IIIB Skin Melanoma, Stage IIIC Skin Melanoma

Intervention / Treatment
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* Procedure: Diagnostic Microscopy
* Drug: Fluorescein Sodium Injection
* Other: Laboratory Biomarker Analysis
* Procedure: Sentinel Lymph Node Biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 Melanoma tumor that meets indications for a groin SLN biopsy with a >= 10% risk of having metastasis to the draining lymph node (i.e. stage IB to stage IIIC melanoma of the lower body below the umbilicus) Participant must be eligible for a groin sentinel lymph node (SLN) biopsy Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure Exclusion Criteria: Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Sentinel lymph node is deemed inaccessible to microscopic observation during the operative procedure (i.e. sentinel node maps to a deep location or area outside of the groin) Renal dysfunction as defined as creatinine clearance < 70 mL/min by Cockroft-Gault equation Any known allergy or prior reaction to fluorescein, indocyanine green, iodine, or shellfish Unwilling or unable to follow protocol requirements Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to undergo observational study (may also include preoperative testing results including electrocardiogram [EKG], chest x-ray, or pulmonary function tests) Any condition that excludes SLN biopsy as the standard of care (e.g. lymphadenectomy indicated)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diagnostic (intravital microscopy)<br>Patients receive indocyanine green and fluorescein sodium injection IV and then undergo intravital microscopic observation over 15-20 minutes during standard of care sentinel node biopsy. | Procedure: Diagnostic Microscopy<br>* Undergo intravital microscopy<br>Drug: Fluorescein Sodium Injection<br>* Given IV<br>* Other names: Fluorescite;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Procedure: Sentinel Lymph Node Biopsy<br>* Undergo standard of care sentinel node biopsy<br>* Other names: SNB;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of intravital microscopy in characterizing the microvasculature of the SLN in melanoma determined by successful visualization of at least 6 of 10 patients during Part I | The visualization method will be deemed successful in patients with tumor vessel identification, measurement of tumor vessel diameters, determining vessel density, and visualizing fluorescein/indocyanine green within the tumor vessels. | Up to 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Flow kinetics associated with the sentinel lymph node vasculature | Sample sentinel lymph node characteristics obtained from the intervention will be characterized using descriptive statistics (means, medians) and 95% confidence intervals. | Up to 5 years | 
| Survival | Assessed using Kaplan Meier and Proportional Hazards methods. Collected through routine follow-up processes. | Up to 5 years | 
| Time to progression | Assessed using Kaplan Meier and Proportional Hazards methods. Collected through routine follow-up processes. | Up to 5 years | 
| Treatment response | Assessed using Logistic Regression. Collected through routine follow-up processes. | Up to 5 years | 
| Utility of using commonly used fluorescent agents during human intravital microscopy |  | Up to 3 weeks | 
| Vascular blood flow parameters associated with the sentinel lymph node vasculature | Sample sentinel lymph node characteristics obtained from the intervention will be characterized using descriptive statistics (means, medians) and 95% confidence intervals. | Up to 5 years |