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Vaccine Therapy in Treating Patients With Recurrent Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00471471
First received: May 8, 2007
Last updated: August 22, 2012
Last verified: June 2009
  Purpose

RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Giving vaccine therapy together with GM-CSF, CpG 7909, and incomplete Freund's adjuvant may make a stronger immune response and kill more tumor cells.

PURPOSE: This clinical trial is studying the side effects and how well vaccine therapy works in treating patients with recurrent stage III or stage IV melanoma that cannot be removed by surgery.


Condition Intervention
Intraocular Melanoma
Malignant Conjunctival Neoplasm
Melanoma (Skin)
Biological: MART-1:27-35 peptide vaccine
Biological: gp100:209-217(210M) peptide vaccine
Biological: incomplete Freund's adjuvant
Biological: sargramostim
Biological: tyrosinase peptide
Drug: agatolimod sodium
Other: diagnostic laboratory biomarker analysis
Other: flow cytometry
Other: immunologic technique

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety and Immunogenicity of Vaccination With Multi-Epitope Peptide Vaccine Containing MART-1, gp100, and Tyrosinase Peptides Given With the Combination of GMCSF and CpG Oligonucleotide (CpG 7909) in ISA-Oil Adjuvant for Patients With Recurrent Inoperable Stage III or Stage IV Melanoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Safety [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Immunologic response as measured by ELISPOT assays [ Designated as safety issue: No ]
  • Breadth of the immune response as measured by the number of peptides to which the response is observed [ Designated as safety issue: No ]
  • Depth of the immune response [ Designated as safety issue: No ]
  • Objective tumor response (complete response and partial response) by RECIST criteria [ Designated as safety issue: No ]
  • Anti-pigmentary response [ Designated as safety issue: No ]
  • Time to disease progression [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: October 2008
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Determine the safety of a peptide vaccine comprising MART-1:27-35 peptide, gp100:209-217 (210M) peptide, and tyrosinase peptide with sargramostim (GM-CSF) and CpG 7909 emulsified in incomplete Freund's adjuvant in patients with unresectable recurrent stage III or IV melanoma.
  • Determine the efficacy of immunoadjuvants CpG 7909 and GM-CSF, in terms of a strong antigen-specific CD8+ T-cell response, in these patients.
  • Determine the anti-pigmentary response to this regimen in these patients.
  • Determine the anti-tumor response, in terms of objective tumor regression, progression-free survival, and overall survival, in patients treated with this regimen.

OUTLINE: This is a pilot study.

Patients receive peptide vaccine comprising MART-1:27-35 peptide, gp100:209-217 (210M) peptide, and tyrosinase peptide with sargramostim (GM-CSF) and CpG 7909 emulsified in incomplete Freund's adjuvant subcutaneously on days 1 and 15. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline, day 50-53, and day 91-94. Samples are examined by ELISPOT assay to measure lymphocyte immune response and by flow cytometry for biomarker quantification and T-cell response.

After completion of study treatment, patients are followed up periodically for at least 2 years.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed melanoma meeting the following criteria:

    • Unresectable recurrent disease
    • Stage III or IV disease
    • Cutaneous, ocular, or mucosal melanoma
  • Measurable disease as defined by the RECIST criteria
  • HLA-A2 positive
  • Prior brain metastases allowed provided adequate surgical or radiologic treatment for brain disease

PATIENT CHARACTERISTICS:

  • ECOG performance status 0 or 1
  • WBC ≥ 3,000/mm³
  • Lymphocytes ≥ 1,000/mm³
  • Platelet count ≥ 100,000/mm³
  • Creatinine ≤ 1.5 times upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 times ULN
  • AST and ALT ≤ 2.5 times ULN
  • Lactic dehydrogenase ≤ 2.0 times ULN
  • aPTT < 40 seconds
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception for ≥ 1 week before, during, and for ≥ 2 weeks after completion of study therapy
  • No conditions of immunosuppression
  • Negative titers for antinuclear antibody (≤ 1/80) and antidouble stranded DNA (≤ 1/10)
  • No serious illnesses including, but not limited to, any of the following:

    • Bleeding disorders
    • Autoimmune diseases
    • Severe obstructive or restrictive pulmonary diseases
    • Active systemic infections
    • Inflammatory bowel disorders
  • No serious cardiovascular disease including, but not limited to, any of the following:

    • Uncontrolled congestive heart failure
    • Hypertension
    • Cardiac ischemia
    • Myocardial infarction,
    • Severe cardiac arrhythmia
  • HIV1 and 2 negative
  • HTLV-1 negative
  • Hepatitis B and C negative
  • No significant psychiatric disease, medical intervention, or other condition that, in the opinion of the principal investigator, would limit study compliance
  • No active infection within the past week, including unexplained fever (temperature > 38.1°C)

PRIOR CONCURRENT THERAPY:

  • Fully recovered from prior major surgery
  • More than 4 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas), hormonal therapy, radiotherapy, or biological therapy
  • More than 1 week since prior antibiotics
  • More than 28 days since prior investigational agent
  • No prior vaccination with MART-1 (26-35, 27L), gp100 (209-217, 210M), and tyrosinase (368-376, 370D) peptides alone or in combination

    • Patients with history of vaccination with peptides other than MART-1 (26-35, 27L), gp100 (209-217, 210M), and tyrosinase (368-376, 370D) peptides allowed
  • More than 4 weeks since prior and no concurrent systemic immunosuppressive therapy, including steroids

    • Patients on maintenance steroids given at physiologic doses because of adrenal insufficiency are eligible
  • More than 2 weeks since prior and no concurrent treatment with systemic steroids, including oral steroids, continuous use of topical steroid creams or ointments, or any inhaled steroids
  • No concurrent anticoagulants, except to keep an indwelling line patent
  • No other concurrent anticancer therapy, including chemotherapy, immunotherapy, radiotherapy, experimental programs, and/or surgery
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00471471

Locations
United States, Pennsylvania
UPMC Cancer Centers
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Ahmad A. Tarhini, MD, MS University of Pittsburgh
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00471471     History of Changes
Other Study ID Numbers: CDR0000544402, PCI-04173, PCI-IRB-0607048
Study First Received: May 8, 2007
Last Updated: August 22, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
recurrent melanoma
stage IV melanoma
ciliary body and choroid melanoma, medium/large size
extraocular extension melanoma
iris melanoma
recurrent intraocular melanoma
metastatic intraocular melanoma
conjunctival melanoma
stage IIIA melanoma
stage IIIB melanoma
stage IIIC melanoma

Additional relevant MeSH terms:
Conjunctival Neoplasms
Melanoma
Uveal Neoplasms
Conjunctival Diseases
Eye Diseases
Eye Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Uveal Diseases
Freund's Adjuvant
Adjuvants, Immunologic
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 27, 2014