Radiofrequency Therapy-Induced Endogenous Heat-Shock Proteins With or Without Radiofrequency Ablation or Cryotherapy in Treating Patients With Stage IV Melanoma
| Status: | Completed |
|---|---|
| Conditions: | Skin Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - 120 |
| Updated: | 11/2/2018 |
| Start Date: | November 25, 2005 |
| End Date: | May 24, 2018 |
Endogenous Heat-shock Vaccines for Melanoma A Feasibility Study
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.
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.
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.
- 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.
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
We found this trial at
1
site
Mayo Clinic Cancer Center The Mayo Clinic Cancer Center is a National Cancer Institute-designated comprehensive...
Click here to add this to my saved trials
