Radiofrequency Therapy-Induced Endogenous Heat-Shock Proteins With or Without Radiofrequency Ablation or Cryotherapy in Treating Patients With Stage IV Melanoma
Primary Purpose
Melanoma (Skin)
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
sargramostim
immunoenzyme technique
immunohistochemistry staining method
immunologic technique
laboratory biomarker analysis
biopsy
cryosurgery
radiofrequency ablation
Sponsored by

About this trial
This is an interventional treatment trial for Melanoma (Skin) focused on measuring stage IV melanoma, recurrent melanoma
Eligibility Criteria
DISEASE CHARACTERISTICS:
Histologically confirmed malignant melanoma meeting the following criteria:
- Stage IV disease
- Needle/probe accessible lesions of metastatic melanoma evident in the liver (or soft tissue) measuring 2 to 5 cm in size
- HLA-A2 positive
- No known standard therapy that is potentially curative or proven capable of extending life expectancy
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Life expectancy ≥ 12 weeks
- ANC ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin ≥ 10.0 g/dL
- Alkaline phosphatase ≤ 3 times upper limit of normal (ULN)
- AST ≤ 3 times ULN
- Creatinine ≤ 1.5 times ULN
- Prothrombin time ≤ ULN
- Activated partial thromboplastin time ≤ ULN
- No uncontrolled or current infection
- No symptomatic heart disease (i.e., New York Heart Association classification III or IV)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No known immune deficiency
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- More than 4 weeks since prior chemotherapy and recovered
- More than 4 weeks since prior immunotherapy, biologic therapy, or radiotherapy
Sites / Locations
- Mayo Clinic Cancer Center
Outcomes
Primary Outcome Measures
Toxicity
Heat-shock protein levels
Tumor-specific immune response
Extent of lymphocyte infiltration
Tumor response by RECIST criteria
Secondary Outcome Measures
Full Information
NCT ID
NCT00568763
First Posted
December 5, 2007
Last Updated
October 29, 2018
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00568763
Brief Title
Radiofrequency Therapy-Induced Endogenous Heat-Shock Proteins With or Without Radiofrequency Ablation or Cryotherapy in Treating Patients With Stage IV Melanoma
Official Title
Endogenous Heat-shock Vaccines for Melanoma A Feasibility Study
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
November 25, 2005 (Actual)
Primary Completion Date
May 10, 2010 (Actual)
Study Completion Date
May 24, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
RATIONALE: Radiofrequency therapy and radiofrequency ablation use a high-frequency electric current to kill tumor cells. Radiofrequency therapy can also cause the body to produce heat-shock proteins which may help kill more tumor cells. Cryotherapy kills tumor cells by freezing them. It is not yet known whether heat-shock proteins caused by radiofrequency therapy given together with radiofrequency ablation or cryotherapy is more effective in treating stage IV melanoma than radiofrequency therapy-induced heat-shock proteins alone.
PURPOSE: This randomized clinical trial is studying the side effects of radiofrequency therapy-induced endogenous heat-shock proteins when given alone or together with radiofrequency ablation or cryotherapy in treating patients with stage IV melanoma.
Detailed Description
OBJECTIVES:
Determine the safety and feasibility of endogenous heat-shock protein (hsp)70 synthesis at the site of the tumor using radiofrequency therapy (RFT) in patients with stage IV malignant melanoma.
Determine the safety and feasibility of hsp70 release into the circulation using RFT alone vs RFT followed by radiofrequency ablation (RFA) or cryotherapy in these patients.
Determine the feasibility of inducing a primary antitumor immune response using RFT with or without additional local therapy (i.e., RFA or cryotherapy) in these patients.
Gain preliminary insight into the antitumor efficacy of an in vivo heat shock vaccine in these patients.
OUTLINE: Patients are randomized to 1 of 3 arms.
Arm I (closed to enrollment as of 12/7/06): Patients undergo percutaneous biopsy of the target lesion and placement of a localization marker. Patients then undergo radiofrequency therapy (RFT) to the target lesion to induce the production of endogenous heat-shock proteins. After the procedure is completed, patients undergo a second biopsy of the target lesion. Patients also receive an intratumoral injection of sargramostim (GM-CSF) to promote further ablation at the tumor site.
Arm II: Patients undergo percutaneous biopsies and RFT as in arm I followed by radiofrequency ablation of the target lesion. Patients also receive intratumoral GM-CSF as in arm I.
Arm III: Patients undergo percutaneous biopsies and RFT as in arm I followed by cryoablation of the target lesion. Patients also receive intratumoral GM-CSF as in arm I.
Tumor tissue samples are obtained by core biopsy immediately before and immediately after RFT for RNA and protein analysis. Tissue samples are assessed by immunohistochemistry for tumor phenotype (i.e., MART-1, tyrosinase, or gp100) and for quantification of infiltrating lymphocytes. Peripheral blood samples are also obtained before and after treatment and periodically during study for immunologic analyses. Peripheral blood-derived lymphocytes are tested with a panel of monoclonal antibodies to estimate the percentages of cytotoxic T lymphocytes (CTLs), including CD4+ and CD8+ T cells as well as B cells, monocytes, and dendritic cells. In addition, assays are performed to estimate T-cell responses to polyclonal stimulus (i.e., PHA), recall antigens (i.e., tetanus toxoid), and HLA alloantigens. Estimates of peptide-specific CTLs are also obtained by enzyme-linked immunosorbent spot assays after in vitro stimulation with peptide-sensitized stimulator cells. Antibodies to extractable nuclear antigens (ENA) and antinuclear antibodies (ANA) will also be evaluated. GM-CSF levels and Hsp70 is assessed in tumor cells and peripheral blood by flow cytometry or enzyme-linked immunosorbent assays.
After completion of study therapy, patients are followed periodically for up to 3 years.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma (Skin)
Keywords
stage IV melanoma, recurrent melanoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Allocation
Randomized
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Biological
Intervention Name(s)
sargramostim
Intervention Type
Other
Intervention Name(s)
immunoenzyme technique
Intervention Type
Other
Intervention Name(s)
immunohistochemistry staining method
Intervention Type
Other
Intervention Name(s)
immunologic technique
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Type
Procedure
Intervention Name(s)
biopsy
Intervention Type
Procedure
Intervention Name(s)
cryosurgery
Intervention Type
Procedure
Intervention Name(s)
radiofrequency ablation
Primary Outcome Measure Information:
Title
Toxicity
Title
Heat-shock protein levels
Title
Tumor-specific immune response
Title
Extent of lymphocyte infiltration
Title
Tumor response by RECIST criteria
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS:
Histologically confirmed malignant melanoma meeting the following criteria:
Stage IV disease
Needle/probe accessible lesions of metastatic melanoma evident in the liver (or soft tissue) measuring 2 to 5 cm in size
HLA-A2 positive
No known standard therapy that is potentially curative or proven capable of extending life expectancy
PATIENT CHARACTERISTICS:
ECOG performance status 0-2
Life expectancy ≥ 12 weeks
ANC ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Hemoglobin ≥ 10.0 g/dL
Alkaline phosphatase ≤ 3 times upper limit of normal (ULN)
AST ≤ 3 times ULN
Creatinine ≤ 1.5 times ULN
Prothrombin time ≤ ULN
Activated partial thromboplastin time ≤ ULN
No uncontrolled or current infection
No symptomatic heart disease (i.e., New York Heart Association classification III or IV)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No known immune deficiency
PRIOR CONCURRENT THERAPY:
See Disease Characteristics
More than 4 weeks since prior chemotherapy and recovered
More than 4 weeks since prior immunotherapy, biologic therapy, or radiotherapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Svetomir N Markovic, MD, PhD
Organizational Affiliation
Mayo Clinic
Official's Role
Study Chair
Facility Information:
Facility Name
Mayo Clinic Cancer Center
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
28679643
Citation
Domingo-Musibay E, Heun JM, Nevala WK, Callstrom M, Atwell T, Galanis E, Erickson LA, Markovic SN. Endogenous Heat-Shock Protein Induction with or Without Radiofrequency Ablation or Cryoablation in Patients with Stage IV Melanoma. Oncologist. 2017 Sep;22(9):1026-e93. doi: 10.1634/theoncologist.2017-0060. Epub 2017 Jul 5.
Results Reference
derived
Learn more about this trial
Radiofrequency Therapy-Induced Endogenous Heat-Shock Proteins With or Without Radiofrequency Ablation or Cryotherapy in Treating Patients With Stage IV Melanoma
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