Radiofrequency Therapy-Induced Endogenous Heat-Shock Proteins With or Without Radiofrequency Ablation or Cryotherapy in Treating Patients With Stage IV Melanoma
Condition: Melanoma (Skin)
MeSH terms: Melanoma
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): sargramostim; immunoenzyme technique; immunohistochemistry staining method; immunologic technique; laboratory biomarker analysis; biopsy; cryosurgery; radiofrequency ablation
Intervention type(s): Biological; Other; Other; Other; Other; Procedure; Procedure; Procedure
Intervention MeSH terms: Sargramostim
Allocation: Randomized
Primary purpose: Treatment
Keywords: stage IV melanoma; recurrent melanoma