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

Early Phase 1

Completed

• Conditions: Recurrent Melanoma; Stage IIA Melanoma; Stage IIB Melanoma; Stage IIC Melanoma; Stage IIIA Melanoma; Stage IIIB Melanoma; Stage IIIC Melanoma; Stage IV Melanoma
• Interventions: Drug: Montanide ISA 51 VG; Biological: MART-1 antigen; Other: laboratory biomarker analysis; Drug: resiquimod

• Registration Number: NCT01748747
• Lead Sponsor: Mayo Clinic

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.

Study Timeline

• Study Start: 2012-10
• Study First Submitted: 2012-12-10
• Study First Submitted QC: 2012-12-10
• Study First Posted: 2012-12-12
• Primary Completion: 2014-12-14
• Study Completion: 2017-03-30
• Status Verified: 2018-10
• Last Update Submitted: 2018-10-04
• Last Update Posted: 2018-10-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (MART-1 antigen, Gag:267-274 peptide vaccine)	MART-1 antigen	Patients receive MART-1 antigen and Gag:267-274 peptide vaccine emulsified in Montanide ISA 51 VG SC on day 1.
Arm I (MART-1 antigen, Gag:267-274 peptide vaccine)	laboratory biomarker analysis	Patients receive MART-1 antigen and Gag:267-274 peptide vaccine emulsified in Montanide ISA 51 VG SC on day 1.
Arm II (MART-1 antigen, resiquimod, Montanide ISA 51 VG)	MART-1 antigen	Patients receive MART-1 antigen emulsified in Montanide ISA 51 VG SC followed by resiquimod applied topically on day 1.
Arm II (MART-1 antigen, resiquimod, Montanide ISA 51 VG)	laboratory biomarker analysis	Patients receive MART-1 antigen emulsified in Montanide ISA 51 VG SC followed by resiquimod applied topically on day 1.
Arm III (MART-1 antigen, Gag:267-274 peptide, resiquimod)	MART-1 antigen	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.
Arm III (MART-1 antigen, Gag:267-274 peptide, resiquimod)	laboratory biomarker analysis	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.
Arm III (MART-1 antigen, Gag:267-274 peptide, resiquimod)	Montanide ISA 51 VG	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.
Arm III (MART-1 antigen, Gag:267-274 peptide, resiquimod)	resiquimod	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.
Arm I (MART-1 antigen, Gag:267-274 peptide vaccine)	Montanide ISA 51 VG	Patients receive MART-1 antigen and Gag:267-274 peptide vaccine emulsified in Montanide ISA 51 VG SC on day 1.
Arm II (MART-1 antigen, resiquimod, Montanide ISA 51 VG)	Montanide ISA 51 VG	Patients receive MART-1 antigen emulsified in Montanide ISA 51 VG SC followed by resiquimod applied topically on day 1.

Primary Outcome Measures

Name	Time	Method
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	Up to 12 months	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

Name	Time	Method
Disease-free survival	From registration to recurrence, new primary, or death due to any cause, assessed up to 24 months	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	Up to 24 months	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.

Trial Locations

Locations (1)

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States