Intravital Microscopy in Human Solid Tumors

Study Overview
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Brief Summary
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This study will investigate the tumor-associated vasculature of patients with solid tumors. The investigators will use a technology known as intravital microscopy (IVM) in order to visualize in real-time the vessels associated with solid tumors. The IVM observations may determine if an individual patient's tumor vessels would be amenable to receiving systemic therapy, based on the functionality of the vessels.

Detailed Description
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Primary objective(s): To determine the feasibility and clinical utility of performing HIVM in patients with solid tumors during standard course of treatment (surgical resection). Secondary objective(s): Compare the microscopic observation of the tumor-associated vessels with normal tissue (e.g. peritoneal surface) in each individual subject. Correlate the microscopic observations of the tumor-associated vessels with pathologic grade of tumor. To correlate the microscopic observation of the microvasculature with tumor-specific and overall survival.

Official Title
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Intravital Microscopy (IVM) in Human Solid Tumors

Conditions
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Solid Tumor, Adult

Intervention / Treatment
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* Device: Human Intravital Microscopy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years of age. ECOG Performance Status of ≤ 2. Measurable tumor by direct visualization requiring surgical resection in the OR. Tumor types of origin include gastric, pancreatic, hepatobiliary, colorectal, and sarcoma. Tumors may be primary or metastatic to solid or hollow intra-abdominal organs. Subject must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent. Subject must have a skin prick test pre-operatively (at the time of the preoperative visit and after signed informed consent for entry into this clinical trial is given) to determine any sensitivity to fluorescein. 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. Renal dysfunction as defined as a GFR < 45. Liver dysfunction as defined by Child-Pugh score > 5, or LFT's 1.5x above normal range. Any known allergy or prior reaction to fluorescein or a positive skin prick test to fluorescein. Pregnant or nursing female subjects, determined preoperatively with a urine pregnancy test. Unwilling or unable to follow protocol requirements. Any condition which in the Investigators' opinion deems the patient unsuitable (e.g., abnormal EKG, including T wave inversion, elevated T waves, prolonged QRS interval, or conduction blocks) or that requires further work-up (including cardiac echo or stress test). Any condition that excludes surgery as the standard of care (e.g. high disease burden where alternative treatments like systemic chemotherapy would be preferred).

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: Arm 1<br>Determine the feasibility and clinical utility of performing Human Intravital Microscopy (HIVM) in patients with solid tumors during surgical resection. | Device: Human Intravital Microscopy<br>* Intravital microscopy (IVM) allows real-time, direct visualization of microscopic blood vessels and calculation of blood flow.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. Tumor vessel identification (# tumor vessels visualized per high power field) | Identify and measure vessels associated with solid tumors | 12-15 minutes | 
| 2. Tumor vessel density (# tumor vessels per square cm area observed) | Determine vessel density per 10x field | 12-15 minutes | 
| 3. Fluorescent dye uptake (# tumor vessels with fluorescent dye uptake and # tumor vessels without dye uptake) | Visualize vital dye within the vessels (fluorescein) | 12-15 minutes | 
| 4. Tumor blood flow (velocity, mm/sec) | Calculate the blood flow velocity of the vessels and tissue penetration of fluorescent dye as a marker of vessel permeability. | 12-15 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 5. Post-operative comparison of the microvasculature of tumor with normal tissue | Post-operative comparison of the microvasculature of tumor with normal tissue (e.g. peritoneum) in each individual subject using vessel diameters, vessel density, detection of intravital dye and flow rates. | 15-20 minutes | 
| 6. Post-operative correlation of the microvasculature with pathologic features of the tumor implants (i.e. tumor grade) at the time of the final pathology report (5-7 days after surgery). | The investigators will determine if there is a correlation between the microvasculature with pathologic features of the tumor implants (i.e. tumor grade) at the time of the final pathology report (5-7 days after surgery). | 5-7 days | 
| Post-operative correlation of the microscopic observation of the tumor microvasculature tumor-specific and overall survival. | The investigators will determine if there is a correlation between the microscopic observation of the tumor microvasculature tumor-specific and overall survival. | 5 years |