Intravital Microscopy for Identifying Tumor Vessels in Patients With Stage IA-IV Melanoma That is Being Removed by Surgery

Study Overview
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Brief Summary
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This pilot clinical trial studies intravital microscopy for identifying tumor vessels in patients with stage IA-IV melanoma that is being removed by surgery. New imaging procedures, such as intravital microscopy, may determine the extent of melanoma.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the feasibility of performing intravital microscopy on accessible human melanoma tumors during their standard course of treatment (i.e., wide local excision). (Part I) SECONDARY OBJECTIVES: I. To determine the blood flow velocity of the tumor vessels and tissue penetration of fluorescein (fluorescein sodium) as a marker of tumor vessel permeability. (Part II) OUTLINE: Patients receive fluorescein sodium intravenously (IV) followed by intravital microscopic observation over 10-15 minutes during excision of the melanoma. After completion of study treatment, patients are followed up at 3 weeks and then periodically for 5 years.

Official Title
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A Pilot Study of Feasibility of Performing Intravital Microscopy in Melanoma Patients

Conditions
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Recurrent Melanoma, Stage IA Skin Melanoma, 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, Stage IV Skin Melanoma

Intervention / Treatment
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* Procedure: Diagnostic Microscopy
* Drug: Fluorescein Sodium Injection
* Other: Laboratory Biomarker Analysis
* Procedure: Therapeutic Conventional Surgery


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 Have measurable disease in their skin by direct visualization (visible lesion typically > 0.5 cm in maximal diameter); to perform a microscopic observation, the lesion will have to be visible by the naked eye, lined-up visually, and be able to interface with the microscope objective; a melanoma lesion that is smaller than 0.5 cm in diameter would present several obstacles to obtaining a reliable microscopic observation in the operating room; therefore, a visible lesion, at a minimum of 0.5 cm in diameter, is proposed for this study Melanoma tumor that requires a wide local excision in the operating room; this may include any stage of melanoma from stage IA to stage IV that requires a wide excision in the operating room Subject 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 To determine any sensitivity to fluorescein, subject must have a skin prick test preoperatively (at the time of the preoperative visit and after signed informed consent for entry into this clinical trial is given); a negative skin prick test to fluorescein is an inclusion criteria 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 Melanoma deposit is deemed inaccessible to microscopic observation during the operative procedure (i.e., lesion is less than 0.5 cm or is not clearly visible to the naked eye) Renal dysfunction as defined as a glomerular filtration rate (GFR) < 70 Any known allergy or prior reaction to fluorescein; also, a positive skin prick test to fluorescein is considered an exclusion criteria and the patient would not be eligible for entry into this study Pregnant or nursing female subjects Unwilling or unable to follow protocol requirements Any condition which in the Investigator's opinion deems the subject an unsuitable candidate to undergo observational study (may also include preoperative testing results including electrocardiogram [EKG], chest x-ray, or pulmonary function tests that preclude a wide excision in the operating room)

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: Diagnosis (intravital microscopy)<br>Patients receive fluorescein sodium IV followed by intravital microscopic observation over 10-15 minutes during excision of the melanoma. | 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: Therapeutic Conventional Surgery<br>* Undergo surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Successful Intravital Microscopy on Accessible Human Melanoma Tumors During Standard Local Excision | A successful intravital microscopic observation will include the ability to identify tumor vessels, measure tumor vessel diameters, determine vessel density per 10 x field and visualize fluorescein within the tumor vessels. | Up to 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Any Adverse Event | Percentage of participants with any adverse event. Described using upper one-sided 95% Clopper Pearson confidence limits. | Up to 5 years | 
| Blood Flow Rates | Sample tumor characteristics obtained from the intervention will be characterized using descriptive statistics (mean, medians) and 95% confidence intervals. | Up to 2 months | 
| Complication Rate | Number of participants with an event that would disrupt the standard surgical procedure or create an adverse event that would not be anticipated from the standard surgery. | Up to 5 years | 
| Median Overall Survival | Assessed using Kaplan Meier and Proportional Hazards methods. Collected through routine follow-up processes. | Up to 5 years | 
| Median Progression Free Survival | Assessed using Kaplan Meier and Proportional Hazards methods. Collected through routine follow-up processes. | Up to 5 years | 
| Percentage of Participants With Treatment Response | Treatment response was based upon the presence of a recurrence of the melanoma at either primary or metastatic sites. | Up to 5 years | 
| Tumor Vasculature | Sample tumor characteristics obtained from the intervention will be characterized using descriptive statistics (mean, medians) and 95% confidence intervals. | Up to 2 months |