Radiofrequency Therapy-Induced Endogenous Heat-Shock Proteins With or Without Radiofrequency Ablation or Cryotherapy in Treating Patients With Stage IV Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00568763
Recruitment Status : Completed
First Posted : December 6, 2007
Last Update Posted : June 8, 2018
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

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.

Condition or disease Intervention/treatment Phase
Melanoma (Skin) Biological: sargramostim Other: immunoenzyme technique Other: immunohistochemistry staining method Other: immunologic technique Other: laboratory biomarker analysis Procedure: biopsy Procedure: cryosurgery Procedure: radiofrequency ablation Not Applicable

Detailed Description:


  • 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: Randomized
Primary Purpose: Treatment
Official Title: Endogenous Heat-shock Vaccines for Melanoma A Feasibility Study
Actual Study Start Date : November 25, 2005
Actual Primary Completion Date : May 10, 2010
Actual Study Completion Date : May 24, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma Shock

Primary Outcome Measures :
  1. Toxicity
  2. Heat-shock protein levels
  3. Tumor-specific immune response
  4. Extent of lymphocyte infiltration
  5. Tumor response by RECIST criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • See Disease Characteristics
  • More than 4 weeks since prior chemotherapy and recovered
  • More than 4 weeks since prior immunotherapy, biologic therapy, or radiotherapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00568763

United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Study Chair: Svetomir N Markovic, MD, PhD Mayo Clinic

Responsible Party: Mayo Clinic Identifier: NCT00568763     History of Changes
Other Study ID Numbers: CDR0000579004
P30CA015083 ( U.S. NIH Grant/Contract )
MC0474 ( Other Identifier: Mayo Clinic Cancer Center )
1189-05 ( Other Identifier: Mayo Clinic IRB )
NCI-2009-01304 ( Registry Identifier: NCI CTRP )
First Posted: December 6, 2007    Key Record Dates
Last Update Posted: June 8, 2018
Last Verified: June 2018

Keywords provided by Mayo Clinic:
stage IV melanoma
recurrent melanoma

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas