Trial Information

Endogenous Heat-shock Vaccines for Melanoma A Feasibility Study

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.