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

• Sponsor: Roswell Park Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01886235
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 10
• Location: 1
• Arm: 1
• Actual Duration (Months): 80
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Procedure: Diagnostic Microscopy; Drug: Fluorescein Sodium Injection; Other: Laboratory Biomarker Analysis; Procedure: Therapeutic Conventional Surgery	N/A

Detailed Description

PRIMARY OBJECTIVES:

1. 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

SECONDARY OBJECTIVES:

1. 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 Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: A Pilot Study of Feasibility of Performing Intravital Microscopy in Melanoma Patients
• Actual Study Start Date: Sep 4, 2013
• Actual Primary Completion Date: Jun 16, 2015
• Actual Study Completion Date: May 6, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Diagnosis (intravital microscopy) Patients receive fluorescein sodium IV followed by intravital microscopic observation over 10-15 minutes during excision of the melanoma.	Procedure: Diagnostic Microscopy; Undergo intravital microscopy; Drug: Fluorescein Sodium Injection; Given IV; Other Names: Fluorescite ; Other: Laboratory Biomarker Analysis; Correlative studies; Procedure: Therapeutic Conventional Surgery; Undergo surgery

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Successful Intravital Microscopy on Accessible Human Melanoma Tumors During Standard Local Excision [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.

Secondary Outcome Measures

1. "Percentage of Participants With Any Adverse Event [Up to 5 years]

   Percentage of participants with any adverse event. Described using upper one-sided 95% Clopper Pearson confidence limits.

2. Blood Flow Rates [Up to 2 months]

   Sample tumor characteristics obtained from the intervention will be characterized using descriptive statistics (mean, medians) and 95% confidence intervals.

3. Complication Rate [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.

4. Median Overall Survival [Up to 5 years]

   Assessed using Kaplan Meier and Proportional Hazards methods. Collected through routine follow-up processes.

5. Median Progression Free Survival [Up to 5 years]

   Assessed using Kaplan Meier and Proportional Hazards methods. Collected through routine follow-up processes.

6. Percentage of Participants With Treatment Response [Up to 5 years]

   Treatment response was based upon the presence of a recurrence of the melanoma at either primary or metastatic sites.

7. Tumor Vasculature [Up to 2 months]

   Sample tumor characteristics obtained from the intervention will be characterized using descriptive statistics (mean, medians) and 95% confidence intervals.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Roswell Park Cancer Institute	Buffalo	New York	United States	14263

Sponsors and Collaborators

• Roswell Park Cancer Institute
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Joseph Skitzki, Roswell Park Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Roswell Park Cancer Institute
• ClinicalTrials.gov Identifier: NCT01886235
• Other Study ID Numbers: I 231512; NCI-2013-01052; I 231512; P30CA016056
• First Posted: Jun 25, 2013
• Last Update Posted: Aug 7, 2020
• Last Verified: Jul 1, 2020

• Additional relevant MeSH terms: Melanoma; Skin Neoplasms

Study Results

Participant Flow

Arm/Group Title	Diagnosis (Intravital Microscopy)
Arm/Group Description	Patients receive fluorescein sodium IV followed by intravital microscopic observation over 10-15 minutes during excision of the melanoma. Diagnostic Microscopy: Undergo intravital microscopy Fluorescein Sodium Injection: Given IV Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo surgery
Period Title: Overall Study
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Diagnosis (Intravital Microscopy)
Arm/Group Description	Patients receive fluorescein sodium IV followed by intravital microscopic observation over 10-15 minutes during excision of the melanoma. Diagnostic Microscopy: Undergo intravital microscopy Fluorescein Sodium Injection: Given IV Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo surgery
Overall Participants	10
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	8 80%
>=65 years	2 20%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.5 (10.6)
Sex: Female, Male (Count of Participants)
Female	5 50%
Male	5 50%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	10 100%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Successful Intravital Microscopy on Accessible Human Melanoma Tumors During Standard Local Excision
Description	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.
Time Frame	Up to 2 months

Outcome Measure Data

Analysis Population Description

All treated and eligible patients

Arm/Group Title	Diagnosis (Intravital Microscopy)
Arm/Group Description	Patients receive fluorescein sodium IV followed by intravital microscopic observation over 10-15 minutes during excision of the melanoma. Diagnostic Microscopy: Undergo intravital microscopy Fluorescein Sodium Injection: Given IV Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo surgery
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	70 700%

2. Secondary Outcome

Title	"Percentage of Participants With Any Adverse Event
Description	Percentage of participants with any adverse event. Described using upper one-sided 95% Clopper Pearson confidence limits.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

All treated and eligible patients.

Arm/Group Title	Diagnosis (Intravital Microscopy)
Arm/Group Description	Patients receive fluorescein sodium IV followed by intravital microscopic observation over 10-15 minutes during excision of the melanoma. Diagnostic Microscopy: Undergo intravital microscopy Fluorescein Sodium Injection: Given IV Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo surgery
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	40 400%

3. Secondary Outcome

Title	Blood Flow Rates
Description	Sample tumor characteristics obtained from the intervention will be characterized using descriptive statistics (mean, medians) and 95% confidence intervals.
Time Frame	Up to 2 months

Outcome Measure Data

Analysis Population Description

All treated and evaluable patients. Only 7 patients had data available, one patient had an unobservable tumor and two patients the fluorscein never made it to the tumor.

Arm/Group Title	Diagnosis (Intravital Microscopy)
Arm/Group Description	Patients receive fluorescein sodium IV followed by intravital microscopic observation over 10-15 minutes during excision of the melanoma. Diagnostic Microscopy: Undergo intravital microscopy Fluorescein Sodium Injection: Given IV Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo surgery
Measure Participants	7
Mean (95% Confidence Interval) [micrometers per second]	270

4. Secondary Outcome

Title	Complication Rate
Description	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.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

All treated and eligible patients

Arm/Group Title	Diagnosis (Intravital Microscopy)
Arm/Group Description	Patients receive fluorescein sodium IV followed by intravital microscopic observation over 10-15 minutes during excision of the melanoma. Diagnostic Microscopy: Undergo intravital microscopy Fluorescein Sodium Injection: Given IV Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo surgery
Measure Participants	10
Count of Participants [Participants]	0 0%

5. Secondary Outcome

Title	Median Overall Survival
Description	Assessed using Kaplan Meier and Proportional Hazards methods. Collected through routine follow-up processes.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

All treated and eligible patients

Arm/Group Title	Diagnosis (Intravital Microscopy)
Arm/Group Description	Patients receive fluorescein sodium IV followed by intravital microscopic observation over 10-15 minutes during excision of the melanoma. Diagnostic Microscopy: Undergo intravital microscopy Fluorescein Sodium Injection: Given IV Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo surgery
Measure Participants	10
Median (95% Confidence Interval) [months]	NA

6. Secondary Outcome

Title	Median Progression Free Survival
Description	Assessed using Kaplan Meier and Proportional Hazards methods. Collected through routine follow-up processes.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

All treated and eligible patients

Arm/Group Title	Diagnosis (Intravital Microscopy)
Arm/Group Description	Patients receive fluorescein sodium IV followed by intravital microscopic observation over 10-15 minutes during excision of the melanoma. Diagnostic Microscopy: Undergo intravital microscopy Fluorescein Sodium Injection: Given IV Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo surgery
Measure Participants	10
Median (95% Confidence Interval) [months]	NA

7. Secondary Outcome

Title	Percentage of Participants With Treatment Response
Description	Treatment response was based upon the presence of a recurrence of the melanoma at either primary or metastatic sites.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

All treated and eligible patients

Arm/Group Title	Diagnosis (Intravital Microscopy)
Arm/Group Description	Patients receive fluorescein sodium IV followed by intravital microscopic observation over 10-15 minutes during excision of the melanoma. Diagnostic Microscopy: Undergo intravital microscopy Fluorescein Sodium Injection: Given IV Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo surgery
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	0 0%

8. Secondary Outcome

Title	Tumor Vasculature
Description	Sample tumor characteristics obtained from the intervention will be characterized using descriptive statistics (mean, medians) and 95% confidence intervals.
Time Frame	Up to 2 months

Outcome Measure Data

Analysis Population Description

Stringent dosing requirements precluded assessment of tumor vasculature endpoints. These measurements will be addressed in future studies.

Arm/Group Title	Diagnosis (Intravital Microscopy)
Arm/Group Description	Patients receive fluorescein sodium IV followed by intravital microscopic observation over 10-15 minutes during excision of the melanoma. Diagnostic Microscopy: Undergo intravital microscopy Fluorescein Sodium Injection: Given IV Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo surgery
Measure Participants	0

Adverse Events

Arm/Group Title	Diagnosis (Intravital Microscopy)
Arm/Group Description	Patients receive fluorescein sodium IV followed by intravital microscopic observation over 10-15 minutes during excision of the melanoma. Diagnostic Microscopy: Undergo intravital microscopy Fluorescein Sodium Injection: Given IV Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo surgery
All Cause Mortality
	Diagnosis (Intravital Microscopy)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Diagnosis (Intravital Microscopy)
	Affected / at Risk (%)	# Events
Total	1/10 (10%)
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration	1/10 (10%)	1
Other (Not Including Serious) Adverse Events
	Diagnosis (Intravital Microscopy)
	Affected / at Risk (%)	# Events
Total	4/10 (40%)
Blood and lymphatic system disorders
Anaemia	1/10 (10%)	3
Cardiac disorders
Sinus bradycardia	1/10 (10%)	1
General disorders
Oedema peripheral	1/10 (10%)	1
Pyrexia	1/10 (10%)	2
Infections and infestations
Skin infection	1/10 (10%)	2
Injury, poisoning and procedural complications
Incision site pain	1/10 (10%)	1
Wound dehiscence	1/10 (10%)	1
Investigations
Alanine aminotransferase increased	1/10 (10%)	1
Aspartate aminotransferase increased	1/10 (10%)	1
Blood alkaline phosphatase increased	1/10 (10%)	1
Blood magnesium increased	1/10 (10%)	1
Blood potassium decreased	1/10 (10%)	1
Blood sodium decreased	1/10 (10%)	1
Troponin increased	1/10 (10%)	1
Metabolism and nutrition disorders
Hypoalbuminaemia	1/10 (10%)	1
Hypocalcaemia	1/10 (10%)	1
Musculoskeletal and connective tissue disorders
Joint range of motion decreased	1/10 (10%)	1
Psychiatric disorders
Insomnia	1/10 (10%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.