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
Conditions
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.
Interventions
PROCEDUREDiagnostic Microscopy
Undergo intravital microscopy
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
PROCEDURETherapeutic Conventional Surgery
Undergo surgery
Sponsors
National Cancer Institute (NCI)
Roswell Park Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| Median Overall Survival | Up to 5 years | Assessed using Kaplan Meier and Proportional Hazards methods. Collected through routine follow-up processes. |
| 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. |
| 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. |
| 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. |
| Median Progression Free Survival | Up to 5 years | Assessed using Kaplan Meier and Proportional Hazards methods. Collected through routine follow-up processes. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Diagnosis (Intravital Microscopy) 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 | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Diagnosis (Intravital Microscopy) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 58.5 years STANDARD_DEVIATION 10.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 10 |
| serious Total, serious adverse events | 1 / 10 |
Outcome results
Primary
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.
Time frame: Up to 2 months
Population: All treated and eligible patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diagnosis (Intravital Microscopy) | Percentage of Participants With Successful Intravital Microscopy on Accessible Human Melanoma Tumors During Standard Local Excision | 70 percentage of participants |
Secondary
Blood Flow Rates
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
Population: 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 | Measure | Value (MEAN) |
|---|---|---|
| Diagnosis (Intravital Microscopy) | Blood Flow Rates | 270 micrometers per second |
Secondary
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.
Time frame: Up to 5 years
Population: All treated and eligible patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Diagnosis (Intravital Microscopy) | Complication Rate | 0 Participants |
Secondary
Median Overall Survival
Assessed using Kaplan Meier and Proportional Hazards methods. Collected through routine follow-up processes.
Time frame: Up to 5 years
Population: All treated and eligible patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Diagnosis (Intravital Microscopy) | Median Overall Survival | NA months |
Secondary
Median Progression Free Survival
Assessed using Kaplan Meier and Proportional Hazards methods. Collected through routine follow-up processes.
Time frame: Up to 5 years
Population: All treated and eligible patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Diagnosis (Intravital Microscopy) | Median Progression Free Survival | NA months |
Secondary
Percentage of Participants With Any Adverse Event
Percentage of participants with any adverse event. Described using upper one-sided 95% Clopper Pearson confidence limits.
Time frame: Up to 5 years
Population: All treated and eligible patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diagnosis (Intravital Microscopy) | Percentage of Participants With Any Adverse Event | 40 percentage of participants |
Secondary
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.
Time frame: Up to 5 years
Population: All treated and eligible patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diagnosis (Intravital Microscopy) | Percentage of Participants With Treatment Response | 0 percentage of participants |
Secondary
Tumor Vasculature
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
Population: Stringent dosing requirements precluded assessment of tumor vasculature endpoints. These measurements will be addressed in future studies.