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Endogenous Heat-shock Vaccines for Melanoma A Feasibility Study

18 Years
Open (Enrolling)
Melanoma (Skin)

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Trial Information

Endogenous Heat-shock Vaccines for Melanoma A Feasibility Study


- 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

- 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

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.

Inclusion Criteria


- 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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Outcome Measure:


Safety Issue:


Principal Investigator

Svetomir N Markovic, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic


United States: Federal Government

Study ID:




Start Date:

November 2005

Completion Date:

Related Keywords:

  • Melanoma (Skin)
  • stage IV melanoma
  • recurrent melanoma
  • Melanoma



Mayo Clinic Cancer Center Rochester, Minnesota  55905