Melanoma (Skin)Phase 1NCT00568763
Radiofrequency Therapy-Induced Endogenous Heat-Shock Proteins With or Without Radiofrequency Ablation or Cryotherapy in Treating Patients With Stage IV Melanoma
A Phase 1 study testing sargramostim, immunoenzyme technique and immunohistochemistry staining method in people with Melanoma (Skin), run by Mayo Clinic at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Melanoma (Skin)
- What is being tested?
- sargramostim, immunoenzyme technique and immunohistochemistry staining method
- Type of treatment
- Surgery or procedure
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Nov 2005to 24 May 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic Cancer Center
Rochester, Minnesota, 55905
About this study
Official title: 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.
Read the 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.
- Conditions
- Melanoma (Skin)
- Being tested
- sargramostim, immunoenzyme technique, immunohistochemistry staining method, immunologic technique, laboratory biomarker analysis
- Keywords
- stage IV melanoma, recurrent melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sargramostimBiological
immunoenzyme techniqueOther
immunologic techniqueOther
laboratory biomarker analysisOther
biopsyProcedure or surgery
cryosurgeryProcedure or surgery
radiofrequency ablationProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity
Heat-shock protein levels
Tumor-specific immune response
Extent of lymphocyte infiltration
Tumor response by RECIST criteria
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2007 (estimated)
- Study start25 Nov 2005
- Primary completion10 May 2010
- Study completion24 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Melanoma (Skin)Studies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Svetomir N Markovic, MD, PhD, Study chair, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00568763
- Sponsor's protocol ID
- CDR0000579004
- Other IDs
- P30CA015083, MC0474, 1189-05, NCI-2009-01304
- Status last verified
- Oct 2018
- First submitted
- 5 Dec 2007
- Last updated
- 31 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Domingo-Musibay E, Heun JM, Nevala WK, Callstrom M, Atwell T, Galanis E, Erickson LA, Markovic SN. Endogenous Heat-Shock Protein Induction with or Without Radiofrequency Ablation or Cryoablation in Patients with Stage IV Melanoma. Oncologist. 2017 Sep;22(9):1026-e93. doi: 10.1634/theoncologist.2017-0060. Epub 2017 Jul 5.
PubMed 28679643
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endogenous Heat-shock Vaccines for Melanoma A Feasibility Study
- ClinicalTrials.gov ID
- NCT00568763
- Acronym / sponsor ID
- CDR0000579004
- Conditions
- Melanoma (Skin)
- Keywords
- stage IV melanoma, recurrent melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 25 Nov 2005 (actual)
- Primary completion
- 10 May 2010 (actual)
- Study completion
- 24 May 2018 (actual)
- First posted
- 6 Dec 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sargramostim | Biological | – |
| immunoenzyme technique | Other | – |
| immunohistochemistry staining method | Other | – |
| immunologic technique | Other | – |
| laboratory biomarker analysis | Other | – |
| biopsy | Procedure or surgery | – |
| cryosurgery | Procedure or surgery | – |
| radiofrequency ablation | Procedure or surgery | – |
Primary outcome
Toxicity
Heat-shock protein levels
Tumor-specific immune response
Extent of lymphocyte infiltration
Tumor response by RECIST criteria
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2018.
- Derived from this study: PubMed 28679643Domingo-Musibay E, Heun JM, Nevala WK, Callstrom M, Atwell T, Galanis E, Erickson LA, Markovic SN. Endogenous Heat-Shock Protein Induction with or Without Radiofrequency Ablation or Cryoablation in Patients with Stage IV Melanoma. Oncologist. 2017 Sep;22(9):1026-e93. doi: 10.1634/theoncologist.2017-0060. Epub 2017 Jul 5.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Svetomir N Markovic, MD, PhD study chair
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing sargramostim, immunoenzyme technique and immunohistochemistry staining method in people with Melanoma (Skin), run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Toxicity. The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00568763, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2018.