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Vaccine Therapy and Resiquimod in Treating Patients With Stage II-IV Melanoma That Has Been Removed By Surgery

Primary Purpose

Recurrent Melanoma, Stage IIA Melanoma, Stage IIB Melanoma

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Montanide ISA 51 VG
MART-1 antigen
laboratory biomarker analysis
Gag:267-274 peptide vaccine
resiquimod
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Central pathology review submission; this review for MART-1 positivity is mandatory prior to registration to confirm eligibility
  • Human leukocyte antigen (HLA)-A2-positive
  • Histologic proof of stage II, III or IV melanoma that has been completely resected with no current evidence of disease, as demonstrated by imaging within 2 months (stage III or stage IV; must be computed tomography [CT], magnetic resonance imaging [MRI], or positron emission tomography [PET]/CT) or 6 months (stage II; may be chest x-ray, CT, MRI, or PET/CT)
  • Absolute neutrophil count (ANC) >= 1500 mL
  • Hemoglobin (Hgb) > 10 g/dL
  • Platelets (PLT) >= 50,000 mL
  • Aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN)
  • Alkaline phosphatase =< 3 x ULN
  • Ability to provide informed consent
  • Willingness to return to Mayo Clinic Rochester for follow-up
  • Life expectancy >= 12 weeks
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
  • For women of childbearing potential, a negative serum pregnancy test =< 7 days prior to registration
  • Willingness to provide mandatory blood samples for correlative research

Exclusion Criteria:

  • Uncontrolled or current infection
  • Known standard therapy for the patient's disease that is potentially curative or proven capable of extending life expectancy
  • Known allergy to vaccine or adjuvant components

  • Any of the following prior therapies with interval since most recent treatment:

    • Chemotherapy =< 4 weeks prior to registration
    • Biologic therapy or immunotherapy =< 4 weeks prior to registration
    • Radiation therapy =< 4 weeks prior to registration
  • Failure to fully recover from side effects of prior chemotherapy or surgery

  • Any of the following, as this regimen may be harmful to a developing fetus or nursing child:

    • Pregnant women
    • Nursing women
    • Women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.)
  • Known immune deficiency, including human immunodeficiency virus (HIV) infection, as patients with known immune deficiencies will likely not be able to mount an immune response to the study vaccine; in addition, study patients should be naive to the HIV-derived Gag267-274 antigen
  • History of systemic autoimmune disease, as patients with ongoing autoimmunity may be at an increased risk of autoimmune toxicity from the study vaccine
  • Current or recent (=< 4 weeks prior to registration) use of immunosuppressive medications including systemic corticosteroids; (use of corticosteroids in doses not exceeding those used for adrenal replacement is acceptable)
  • History of brain metastases (even if completely resected)
  • Other active malignancy =< 5 years prior to registration; EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: If there is a history or prior malignancy, they must not be receiving other treatment for their cancer

Sites / Locations

  • Mayo Clinic

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Arm I (MART-1 antigen, Gag:267-274 peptide vaccine)

Arm II (MART-1 antigen, resiquimod, Montanide ISA 51 VG)

Arm III (MART-1 antigen, Gag:267-274 peptide, resiquimod)

Arm Description

Patients receive MART-1 antigen and Gag:267-274 peptide vaccine emulsified in Montanide ISA 51 VG SC on day 1.

Patients receive MART-1 antigen emulsified in Montanide ISA 51 VG SC followed by resiquimod applied topically on day 1.

Patients receive MART-1 antigen and Gag:267-274 peptide vaccine peptide vaccine emulsified in Montanide ISA 51 VG SC followed by resiquimod applied topically on day 1.

Outcomes

Primary Outcome Measures

Immune response of each vaccination regimen, defined as a 2-fold or more increase from pre-treatment levels in the frequency of vaccine peptide-specific CTL as measured by tetramer staining
The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true immune response rate will be calculated.

Secondary Outcome Measures

Disease-free survival
Estimated using the method of Kaplan-Meier.
Incidence of adverse events, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.

Full Information

First Posted
December 10, 2012
Last Updated
October 4, 2018
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01748747
Brief Title
Vaccine Therapy and Resiquimod in Treating Patients With Stage II-IV Melanoma That Has Been Removed By Surgery
Official Title
Peptide Vaccine With Resiquimod as an Immune Modulator for Patients With Resected Melanoma: A Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
October 2012 (Actual)
Primary Completion Date
December 14, 2014 (Actual)
Study Completion Date
March 30, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This pilot clinical trial studies vaccine therapy and resiquimod in treating patients with stage II-IV melanoma that has been removed by surgery. Vaccines made from peptides may help the body build an effective immune response to kill tumor cell tumor cells. Biological therapies, such as resiquimod, may stimulate the immune system in different ways and stop tumor cells from growing. It is not yet known whether Gag:267-274 peptide vaccine and resiquimod are more effective when given together or separately
Detailed Description
PRIMARY OBJECTIVES: I. Evaluate the immune response of each immunization regimen and determine an optimal regimen in terms of immune response to recommend for phase II testing. SECONDARY OBJECTIVES: I. Evaluate the adverse events profile of each immunization regimen. II. Evaluate disease-free survival. TERTIARY OBJECTIVES: I. Describe the immunological efficacy of the vaccine preparations with Gag267-274 (Gag:267-274 peptide vaccine) and resiquimod, as measured by the frequency and interferon (IFN)gamma production of peptide-specific cytotoxic T lymphocytes (CTL). II. Examine immune responses to the tumor antigen analog MART-1a (MART-1 antigen) versus the xenoantigen Gag267-274. OUTLINE: Patients are assigned to 1 of 3 treatment groups. ARM I: Patients receive MART-1 antigen and Gag:267-274 peptide vaccine emulsified in Montanide ISA 51 VG subcutaneously (SC) on day 1. ARM II: Patients receive MART-1 antigen emulsified in Montanide ISA 51 VG SC followed by resiquimod applied topically on day 1. ARM III: Patients receive MART-1 antigen and Gag:267-274 peptide vaccine emulsified in Montanide ISA 51 VG SC followed by resiquimod applied topically on day 1. In all arms, treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 3, 6, 9, 12 and 24 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Melanoma, Stage IIA Melanoma, Stage IIB Melanoma, Stage IIC Melanoma, Stage IIIA Melanoma, Stage IIIB Melanoma, Stage IIIC Melanoma, Stage IV Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (MART-1 antigen, Gag:267-274 peptide vaccine)
Arm Type
Experimental
Arm Description
Patients receive MART-1 antigen and Gag:267-274 peptide vaccine emulsified in Montanide ISA 51 VG SC on day 1.
Arm Title
Arm II (MART-1 antigen, resiquimod, Montanide ISA 51 VG)
Arm Type
Experimental
Arm Description
Patients receive MART-1 antigen emulsified in Montanide ISA 51 VG SC followed by resiquimod applied topically on day 1.
Arm Title
Arm III (MART-1 antigen, Gag:267-274 peptide, resiquimod)
Arm Type
Experimental
Arm Description
Patients receive MART-1 antigen and Gag:267-274 peptide vaccine peptide vaccine emulsified in Montanide ISA 51 VG SC followed by resiquimod applied topically on day 1.
Intervention Type
Drug
Intervention Name(s)
Montanide ISA 51 VG
Intervention Description
Given SC
Intervention Type
Biological
Intervention Name(s)
MART-1 antigen
Other Intervention Name(s)
Antigen LB39-AA, Antigen SK29-AA, MART-1, MART-1 Tumor Antigen
Intervention Description
Given SC
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Intervention Type
Biological
Intervention Name(s)
Gag:267-274 peptide vaccine
Other Intervention Name(s)
ILGLNKIV
Intervention Description
Given SC
Intervention Type
Drug
Intervention Name(s)
resiquimod
Other Intervention Name(s)
R 848, S 28463
Intervention Description
Applied topically
Primary Outcome Measure Information:
Title
Immune response of each vaccination regimen, defined as a 2-fold or more increase from pre-treatment levels in the frequency of vaccine peptide-specific CTL as measured by tetramer staining
Description
The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true immune response rate will be calculated.
Time Frame
Up to 12 months
Secondary Outcome Measure Information:
Title
Disease-free survival
Description
Estimated using the method of Kaplan-Meier.
Time Frame
From registration to recurrence, new primary, or death due to any cause, assessed up to 24 months
Title
Incidence of adverse events, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Description
The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.
Time Frame
Up to 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Central pathology review submission; this review for MART-1 positivity is mandatory prior to registration to confirm eligibility Human leukocyte antigen (HLA)-A2-positive Histologic proof of stage II, III or IV melanoma that has been completely resected with no current evidence of disease, as demonstrated by imaging within 2 months (stage III or stage IV; must be computed tomography [CT], magnetic resonance imaging [MRI], or positron emission tomography [PET]/CT) or 6 months (stage II; may be chest x-ray, CT, MRI, or PET/CT) Absolute neutrophil count (ANC) >= 1500 mL Hemoglobin (Hgb) > 10 g/dL Platelets (PLT) >= 50,000 mL Aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN) Alkaline phosphatase =< 3 x ULN Ability to provide informed consent Willingness to return to Mayo Clinic Rochester for follow-up Life expectancy >= 12 weeks Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2 For women of childbearing potential, a negative serum pregnancy test =< 7 days prior to registration Willingness to provide mandatory blood samples for correlative research Exclusion Criteria: Uncontrolled or current infection Known standard therapy for the patient's disease that is potentially curative or proven capable of extending life expectancy Known allergy to vaccine or adjuvant components Any of the following prior therapies with interval since most recent treatment: Chemotherapy =< 4 weeks prior to registration Biologic therapy or immunotherapy =< 4 weeks prior to registration Radiation therapy =< 4 weeks prior to registration Failure to fully recover from side effects of prior chemotherapy or surgery Any of the following, as this regimen may be harmful to a developing fetus or nursing child: Pregnant women Nursing women Women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.) Known immune deficiency, including human immunodeficiency virus (HIV) infection, as patients with known immune deficiencies will likely not be able to mount an immune response to the study vaccine; in addition, study patients should be naive to the HIV-derived Gag267-274 antigen History of systemic autoimmune disease, as patients with ongoing autoimmunity may be at an increased risk of autoimmune toxicity from the study vaccine Current or recent (=< 4 weeks prior to registration) use of immunosuppressive medications including systemic corticosteroids; (use of corticosteroids in doses not exceeding those used for adrenal replacement is acceptable) History of brain metastases (even if completely resected) Other active malignancy =< 5 years prior to registration; EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: If there is a history or prior malignancy, they must not be receiving other treatment for their cancer
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Svetomir Markovic, M.D., Ph.D.
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

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Vaccine Therapy and Resiquimod in Treating Patients With Stage II-IV Melanoma That Has Been Removed By Surgery

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