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

• ClinicalTrials.gov Identifier: NCT01886235
• Recruitment Status: Completed
• First Posted: June 25, 2013
• Results First Posted: June 6, 2017
• Last Update Posted: August 7, 2020
• Sponsor: Roswell Park Cancer Institute
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Roswell Park Cancer Institute

Tracking Information

• First Submitted Date: May 30, 2013
• First Posted Date: June 25, 2013
• Results First Submitted Date: March 30, 2017
• Results First Posted Date: June 6, 2017
• Last Update Posted Date: August 7, 2020
• Actual Study Start Date: September 4, 2013
• Actual Primary Completion Date: June 16, 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 9, 2017)

Percentage of Participants With Successful Intravital Microscopy on Accessible Human Melanoma Tumors During Standard Local Excision [ Time Frame: Up to 2 months ]

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.

Original Primary Outcome Measures (submitted: June 21, 2013)

Feasibility of performing intravital microscopy on accessible human melanoma tumors during standard local excision [ Time Frame: Up to 2 months ]

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.

Current Secondary Outcome Measures (submitted: June 5, 2017)

• "Percentage of Participants With Any Adverse Event [ Time Frame: Up to 5 years ]
  Percentage of participants with any adverse event. Described using upper one-sided 95% Clopper Pearson confidence limits.
• Blood Flow Rates [ Time Frame: Up to 2 months ]
  Sample tumor characteristics obtained from the intervention will be characterized using descriptive statistics (mean, medians) and 95% confidence intervals.
• Complication Rate [ Time Frame: Up to 5 years ]
  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.
• Median Overall Survival [ Time Frame: Up to 5 years ]
  Assessed using Kaplan Meier and Proportional Hazards methods. Collected through routine follow-up processes.
• Median Progression Free Survival [ Time Frame: Up to 5 years ]
  Assessed using Kaplan Meier and Proportional Hazards methods. Collected through routine follow-up processes.
• Percentage of Participants With Treatment Response [ Time Frame: Up to 5 years ]
  Treatment response was based upon the presence of a recurrence of the melanoma at either primary or metastatic sites.
• Tumor Vasculature [ Time Frame: Up to 2 months ]
  Sample tumor characteristics obtained from the intervention will be characterized using descriptive statistics (mean, medians) and 95% confidence intervals.

Original Secondary Outcome Measures (submitted: June 21, 2013)

• Adverse event rate [ Time Frame: Up to 30 days ]
  Described using upper one-sided 95% Clopper Pearson confidence limits.
• Complication Rate [ Time Frame: Up to 30 days ]
  Described using upper one-sided 95% Clopper Pearson confidence limits.
• Tumor Vasculature [ Time Frame: Up to 2 months ]
  Sample tumor characteristics obtained from the intervention will be characterized using descriptive statistics (mean, medians) and 95% confidence intervals.
• Blood Flow Rates [ Time Frame: Up to 2 months ]
  Sample tumor characteristics obtained from the intervention will be characterized using descriptive statistics (mean, medians) and 95% confidence intervals.
• Treatment response [ Time Frame: Up to 5 years ]
  Associations between tumor characteristics and treatment response will be assessed using Logistic Regression methods.
• Time to progression [ Time Frame: Up to 5 years ]
  Assessed using Kaplan Meier and Proportional Hazards methods. Collected through routine follow-up processes. Data will be correlated with findings from the one-time, initial intravital microscopy observation for the defined 5-year period of data collection.
• Survival [ Time Frame: Up to 5 years ]
  Assessed using Kaplan Meier and Proportional Hazards methods. Collected through routine follow-up processes. Data will be correlated with findings from the one-time, initial intravital microscopy observation for the defined 5-year period of data collection.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Intravital Microscopy for Identifying Tumor Vessels in Patients With Stage IA-IV Melanoma That is Being Removed by Surgery
• Official Title: A Pilot Study of Feasibility of Performing Intravital Microscopy in Melanoma Patients
• Brief Summary: 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

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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic

Condition

• 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

• Procedure: Diagnostic Microscopy
  Undergo intravital microscopy
• Drug: Fluorescein Sodium Injection
  Given IV
  Other Name: Fluorescite
• Other: Laboratory Biomarker Analysis
  Correlative studies
• Procedure: Therapeutic Conventional Surgery
  Undergo surgery

Study Arms

Experimental: Diagnosis (intravital microscopy)

Patients receive fluorescein sodium IV followed by intravital microscopic observation over 10-15 minutes during excision of the melanoma.

Interventions:

• Procedure: Diagnostic Microscopy
• Drug: Fluorescein Sodium Injection
• Other: Laboratory Biomarker Analysis
• Procedure: Therapeutic Conventional Surgery

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 9, 2017): 10
• Original Estimated Enrollment (submitted: June 21, 2013): 30
• Actual Study Completion Date: May 6, 2020
• Actual Primary Completion Date: June 16, 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01886235
• Other Study ID Numbers: I 231512; NCI-2013-01052 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); I 231512 ( Other Identifier: Roswell Park Cancer Institute ); P30CA016056 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Roswell Park Cancer Institute
• Study Sponsor: Roswell Park Cancer Institute
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Joseph Skitzki; Roswell Park Cancer Institute

• PRS Account: Roswell Park Cancer Institute
• Verification Date: July 2020