Detection of Immune Cell Infiltration Into Melanomas Treated by PV-10, a Feasibility Study
Primary Purpose
Melanoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PV-10
Surgery
Sponsored by

About this trial
This is an interventional treatment trial for Melanoma focused on measuring skin, metastatic
Eligibility Criteria
Inclusion Criteria:
- Patients who are diagnosed with metastatic melanoma, or who are suspected to have metastatic melanoma and are subsequently proven to have metastatic melanoma by biopsy
- Patients who are planned to undergo surgical resection of at least two foci of palpable cutaneous or subcutaneous metastatic melanoma, for either palliative or therapeutic intent and who consent for preoperative core biopsies of at least two of the resectable lesions prior to surgery
- Patients who have given informed consent to participate in the study
Exclusion Criteria:
- Patients who decline consent for this study
- Patients who have previously received PV-10 therapy
- Patients who were suspected to have metastatic melanoma but are not proven by preoperative biopsy will be replaced and not counted against the accrual goal
- Patients who do not undergo surgical resection of at least two metastatic melanoma lesions including the PV-10 treated lesion will be replaced and not counted against the accrual goal.
- Patients whose melanoma lesions are contiguous with, encompass or infiltrate a major blood vessel
- Patients with an allergy to shellfish due to reported cross-reactivity to PV-10
- Patients with previous sensitivity to iodide
- Patients who do not have a treatable target lesion on a portion of the body other than the head or neck
Concurrent or Intercurrent Illness:
- Patients with a condition of impaired wound healing (such as uncontrolled diabetes mellitus or immunosuppressive steroid dependence) such that in the opinion of the PI it is unsafe for the patient to undergo intralesional PV-10 treatment
- Patients with severe peripheral vascular disease (i.e., claudication occurring after less than 200 meters of walking, rest pain, ischemic ulceration or gangrene)
- Patients with significant concurrent or intercurrent illness, psychiatric disorders, or alcohol or chemical dependence that would, in the opinion of the principal investigator (PI), compromise their safety or compliance or interfere with interpretation of study results
- Patients with uncontrolled thyroid disease, goiter, partial thyroidectomy, previous radioiodine or surgically-treated Graves' hyperthyroidism or cystic fibrosis
- Patients with clinically significant cardiovascular, cerebrovascular, peripheral vascular, renal, gastrointestinal, pulmonary, immunological, endocrine, bone marrow or central nervous system disorders that have required hospitalization within the past 12 months
Pregnancy
- Female patients who have a positive pregnancy test or are lactating.
- Fertile patients who do not agree to use effective contraception (i.e., oral contraceptives, intrauterine devices, double barrier methods such as condoms and diaphragms, abstinence or equivalent measures) beginning at the time of signing consent until after surgery.
- Patients who are dependent upon concomitant medications that predispose to photosensitivity who cannot stop the medication(s) from the period starting 24 hours prior to and ending 24 hours after PV-10 treatment will be excluded.
Sites / Locations
- H. Lee Moffitt Cancer Center and Research Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Immunotherapy Followed by Surgery
Arm Description
PV-10 administration, adverse events assessment, surgery to remove melanoma tumors, follow-up visit.
Outcomes
Primary Outcome Measures
Occurrence of Change in Infiltration of Immune Cells
The pre-treatment blood sample and tumor biopsies will be the control for the post-PV-10 blood samples and resected tumor samples. Tumor core needle biopsies will be collected from the designated injected and uninjected lesions one week prior to intralesional PV-10 therapy. Biopsy samples will be fixed in formalin and embedded in paraffin for immunohistochemical (IHC) staining. On day 0, the injected lesion will be treated with up to 5 mL of PV-10. Seven to 14 days after intralesional PV-10 treatment, the injected and uninjected lesions will be resected. A portion of each tumor equivalent to a core needle biopsy specimen will be fixed in formalin and embedded in paraffin for IHC staining. Immune cell infiltration will be compared between untreated baseline lesions and post-treatment lesions (injected or uninjected) by a blinded pathologist at Moffitt Cancer Center. Measurement is the ordinal level of the T-cell infiltration into tumors with three levels: 0, no brisk, and brisk.
Secondary Outcome Measures
Frequency and Phenotype of Circulating Immune Cells in Peripheral Blood Mononuclear Cells (PBMC)
This secondary endpoint is to enumerate and phenotype patient immune cells in peripheral blood before and after intralesional (IL) PV-10 treatment. The pre-treatment blood sample and tumor biopsies will be the control for the post-PV-10 blood samples and resected tumor samples. T cells will be enumerated and phenotyped in patient blood one week prior to and 7-14 days after intralesional PV-10 therapy. An additional blood draw 14 days post surgery will take place at the end of the study at the time of the surgical follow-up/end of study visit. These samples will be used for in vitro experiments in order to determine the frequency and phenotype of T cells in the blood by flow cytometry.
Titer of Anti-tumor IgG in the Serum
This secondary endpoint is to enumerate anti-tumor immunoglobulin G (IgG) in peripheral blood before and after IL PV-10 treatment. Titer of anti-tumor IgG in the serum prior to, 7-14 days after, and 21-28 days after PV-10 treatment. The pre-treatment blood sample and tumor biopsies will be the control for the post-PV-10 blood samples and resected tumor samples. Serum will be phenotyped from patients one week prior to, 7-14 days after and 21-28 days after IL PV-10 therapy. Serum will be isolated from peripheral blood by centrifugation and will be used to stain patient tumor samples obtained from surgical resection. Bound serum antibodies will be detected by staining with antihuman IgG antibodies and detected by flow cytometry.
Occurrence of Adverse Events (AEs)
Local and systemic toxicity signs and symptoms per the Common Terminology Criteria for Adverse Events v4.0 (CTCAE). Any adverse experiences associated with participation on the trial will be recorded. Adverse events will be assessed within 30 minutes following PV-10 administration and 4 hours after PV-10 administration. Adverse events assessment: Questions about how participants have been feeling and any changes in the way participants feel immediately after the study drug was given and 4 hours later.
Full Information
NCT ID
NCT01760499
First Posted
December 21, 2012
Last Updated
April 18, 2017
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Provectus Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01760499
Brief Title
Detection of Immune Cell Infiltration Into Melanomas Treated by PV-10, a Feasibility Study
Official Title
Detection of Immune Cell Infiltration Into Melanomas Treated by PV-10, a Feasibility Study
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
January 24, 2013 (undefined)
Primary Completion Date
December 29, 2015 (Actual)
Study Completion Date
April 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Provectus Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The main purpose of this study is to find out more about how PV-10 works in melanoma tumors. Researchers also want to find out if there are changes in the body's immune cells (cells that fight infection and illnesses) after PV-10 is given, both inside the melanoma tumors and circulating in the blood.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
Keywords
skin, metastatic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Immunotherapy Followed by Surgery
Arm Type
Experimental
Arm Description
PV-10 administration, adverse events assessment, surgery to remove melanoma tumors, follow-up visit.
Intervention Type
Drug
Intervention Name(s)
PV-10
Other Intervention Name(s)
10% rose bengal disodium
Intervention Description
PV-10 administration: Within one week after completing the screening tests (or the same day as the screening tests), participants will be scheduled to have the study drug (PV-10) administered. PV-10 is given as an injection with a needle, directly into one of the participant's tumors. Participants will be given an injection of a numbing medication before the PV-10 is given.
Intervention Type
Procedure
Intervention Name(s)
Surgery
Intervention Description
Surgery to remove melanoma tumors (Day 7-14): About 7-14 days after the PV-10 is given, participants will have surgery to remove their melanoma tumors. A piece of the tumor that was injected with PV-10 along with a piece of one other tumor will be sent to the laboratory for testing as part of the study.
Primary Outcome Measure Information:
Title
Occurrence of Change in Infiltration of Immune Cells
Description
The pre-treatment blood sample and tumor biopsies will be the control for the post-PV-10 blood samples and resected tumor samples. Tumor core needle biopsies will be collected from the designated injected and uninjected lesions one week prior to intralesional PV-10 therapy. Biopsy samples will be fixed in formalin and embedded in paraffin for immunohistochemical (IHC) staining. On day 0, the injected lesion will be treated with up to 5 mL of PV-10. Seven to 14 days after intralesional PV-10 treatment, the injected and uninjected lesions will be resected. A portion of each tumor equivalent to a core needle biopsy specimen will be fixed in formalin and embedded in paraffin for IHC staining. Immune cell infiltration will be compared between untreated baseline lesions and post-treatment lesions (injected or uninjected) by a blinded pathologist at Moffitt Cancer Center. Measurement is the ordinal level of the T-cell infiltration into tumors with three levels: 0, no brisk, and brisk.
Time Frame
At baseline and 7-14 days after PV-10 treatment
Secondary Outcome Measure Information:
Title
Frequency and Phenotype of Circulating Immune Cells in Peripheral Blood Mononuclear Cells (PBMC)
Description
This secondary endpoint is to enumerate and phenotype patient immune cells in peripheral blood before and after intralesional (IL) PV-10 treatment. The pre-treatment blood sample and tumor biopsies will be the control for the post-PV-10 blood samples and resected tumor samples. T cells will be enumerated and phenotyped in patient blood one week prior to and 7-14 days after intralesional PV-10 therapy. An additional blood draw 14 days post surgery will take place at the end of the study at the time of the surgical follow-up/end of study visit. These samples will be used for in vitro experiments in order to determine the frequency and phenotype of T cells in the blood by flow cytometry.
Time Frame
At baseline, 7-14 days after treatment and 21-28 days after treatment
Title
Titer of Anti-tumor IgG in the Serum
Description
This secondary endpoint is to enumerate anti-tumor immunoglobulin G (IgG) in peripheral blood before and after IL PV-10 treatment. Titer of anti-tumor IgG in the serum prior to, 7-14 days after, and 21-28 days after PV-10 treatment. The pre-treatment blood sample and tumor biopsies will be the control for the post-PV-10 blood samples and resected tumor samples. Serum will be phenotyped from patients one week prior to, 7-14 days after and 21-28 days after IL PV-10 therapy. Serum will be isolated from peripheral blood by centrifugation and will be used to stain patient tumor samples obtained from surgical resection. Bound serum antibodies will be detected by staining with antihuman IgG antibodies and detected by flow cytometry.
Time Frame
At baseline, 7-14 days after treatment and 21-28 days after treatment
Title
Occurrence of Adverse Events (AEs)
Description
Local and systemic toxicity signs and symptoms per the Common Terminology Criteria for Adverse Events v4.0 (CTCAE). Any adverse experiences associated with participation on the trial will be recorded. Adverse events will be assessed within 30 minutes following PV-10 administration and 4 hours after PV-10 administration. Adverse events assessment: Questions about how participants have been feeling and any changes in the way participants feel immediately after the study drug was given and 4 hours later.
Time Frame
During PV-10 administration visit, after 7-14 days, at study end (day 28 or early termination)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients who are diagnosed with metastatic melanoma, or who are suspected to have metastatic melanoma and are subsequently proven to have metastatic melanoma by biopsy
Patients who are planned to undergo surgical resection of at least two foci of palpable cutaneous or subcutaneous metastatic melanoma, for either palliative or therapeutic intent and who consent for preoperative core biopsies of at least two of the resectable lesions prior to surgery
Patients who have given informed consent to participate in the study
Exclusion Criteria:
Patients who decline consent for this study
Patients who have previously received PV-10 therapy
Patients who were suspected to have metastatic melanoma but are not proven by preoperative biopsy will be replaced and not counted against the accrual goal
Patients who do not undergo surgical resection of at least two metastatic melanoma lesions including the PV-10 treated lesion will be replaced and not counted against the accrual goal.
Patients whose melanoma lesions are contiguous with, encompass or infiltrate a major blood vessel
Patients with an allergy to shellfish due to reported cross-reactivity to PV-10
Patients with previous sensitivity to iodide
Patients who do not have a treatable target lesion on a portion of the body other than the head or neck
Concurrent or Intercurrent Illness:
Patients with a condition of impaired wound healing (such as uncontrolled diabetes mellitus or immunosuppressive steroid dependence) such that in the opinion of the PI it is unsafe for the patient to undergo intralesional PV-10 treatment
Patients with severe peripheral vascular disease (i.e., claudication occurring after less than 200 meters of walking, rest pain, ischemic ulceration or gangrene)
Patients with significant concurrent or intercurrent illness, psychiatric disorders, or alcohol or chemical dependence that would, in the opinion of the principal investigator (PI), compromise their safety or compliance or interfere with interpretation of study results
Patients with uncontrolled thyroid disease, goiter, partial thyroidectomy, previous radioiodine or surgically-treated Graves' hyperthyroidism or cystic fibrosis
Patients with clinically significant cardiovascular, cerebrovascular, peripheral vascular, renal, gastrointestinal, pulmonary, immunological, endocrine, bone marrow or central nervous system disorders that have required hospitalization within the past 12 months
Pregnancy
Female patients who have a positive pregnancy test or are lactating.
Fertile patients who do not agree to use effective contraception (i.e., oral contraceptives, intrauterine devices, double barrier methods such as condoms and diaphragms, abstinence or equivalent measures) beginning at the time of signing consent until after surgery.
Patients who are dependent upon concomitant medications that predispose to photosensitivity who cannot stop the medication(s) from the period starting 24 hours prior to and ending 24 hours after PV-10 treatment will be excluded.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amod A. Sarnaik, M.D.
Organizational Affiliation
H. Lee Moffitt Cancer Center and Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Detection of Immune Cell Infiltration Into Melanomas Treated by PV-10, a Feasibility Study
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