Evaluation of the Impact of Adjuvants Accompanying Peptide Immunization in High-Risk Melanoma
Condition: High-Risk Melanoma
MeSH terms: Melanoma
Intervention: gp100:209-217 (210M); Montanide ISA-51; Imiquimod
Intervention description: Apply imiquimod 5% cream to the skin at the site of injection daily for 5 days
Intervention MeSH terms: Imiquimod; Monatide (IMS 3015)
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 104.0
Sex: All
Minimum age: 7 Years
Healthy volunteers: No
Keywords: Disease Free Survival; gp 100:209-217 (210m); Immunologic Response; Adjuvant Therapy; Cutaneous Melanoma; Melanoma

Summary:

      This study will evaluate the immunization effects of a vaccine for patients who are at risk
      for recurrence of their skin cancer. That is, the risk of cancer is higher if melanoma has
      invaded deep into the skin or lymph nodes. Currently, the only therapy that the U.S. Food and
      Drug Administration (FDA) has approved for preventing recurrence of melanoma is
      alpha-interferon. But the research data are controversial. In this study, the vaccine to be
      used, called gp100, contains a piece of a protein called a peptide, which melanoma cancer
      cells produce.

      Patients 16 and older who have had confirmed melanoma surgically removed and whose tissue
      type is tested as being human leukocyte antigen serotype within HLA-A serotype group
      (HLA-A2), through a specific blood test, may be eligible for this study.

      Up to 132 participants will be enrolled. There will be a physical examination and collection
      of blood samples for tests, and making sure that x-rays and scans are current. Patients will
      be randomly assigned to four groups. Group 1 will receive the peptide with an adjuvant
      (assistant) oil-based liquid called Montanide ISA-51, as an injection in the thigh. Group 2
      will receive gp100, Montanide, and a cream called imiquimod, which the FDA has approved for
      treating genital warts and herpes but that may help immune cells in the skin to recognize the
      vaccine. Imiquimod will be applied to the skin for 5 days. Group 3 will receive gp100 mixed
      in salt water given as several mini-doses under the skin of the thigh. Group 4 will also
      receive several mini-doses of gp100 mixed in saline, as well as imiquimod cream applied to
      the skin for 5 days. All patients will receive the gp100 every 3 weeks for 12 weeks. Every
      dose is a cycle, with four cycles considered a course of therapy. If the melanoma does not
      return or patients do not experience side effects from this therapy, then the courses of
      vaccine will repeated for up to 12 cycles of therapy (3 courses over 33 weeks). Side effects
      of the peptide vaccination include local swelling, swelling of local lymph nodes, bruising,
      and pain and redness at the injection sites. There may be chills or fever. Patients will be
      watched closely for such side effects.

      To study how the vaccine changes the action of cells in the immune system, patients' white
      blood cells (lymphocytes) will be obtained, involving a separate informed consent. The
      procedure, called leukaphersis, requires inserting a needle into the arm, to obtain blood
      going into a machine, which divides the blood into red cells, plasma (or the serum part), and
      lymphocytes. The lymphocytes are removed, and the plasma and red cells returned to the
      patient through a second needle in the other arm. Risks associated with the procedure include
      fainting, which can be prevented by patients' eating before coming to the lab, and bleeding
      and infection at the needle site. Patients will undergo leukapheresis will be done about four
      times: before receiving the vaccine, 3 weeks after the first four doses, and then after 8
      cycles and 12 cycles. Patients assigned to the groups receiving imiquimod will be asked to
      record every time they apply that cream and describe any symptoms developed during the study.
      All patients will be watched closely for any sign that their melanoma has returned. Before
      and throughout the study, multiple blood tests will be conducted.

      The vaccine, Montanide, and imiquimod may increase patients' immune system in fighting off
      new tumors, but that is not known now. However, the study may provide information that will
      be useful in treating melanoma patients in the future.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        HLA-A 0201 patients, age greater than or equal to 16 years, primary melanomas with lesions
        that are ulcerated and greater than or equal to 2mm, or any lesions that are greater than
        or equal to 4.0 mm in thickness, or greater than or equal to1 positive lymph node, or local
        recurrence, or resected metastatic disease, within 6 months of surgical resection will be
        considered. Patients must be clinically disease free at the time of protocol entry as
        documented by radiologic studies within 6 weeks of patient entry.

        Serum creatinine of 2.0 mg/dl or less

        Total bilirubin 1.6 mg/dl or less, except for patients with Gilbert's Syndrome who must
        have a total bilirubin less than 3.0 mg/dl.

        WBC 3000/mm^3 or greater,

        Platelet count 90,000 mm^3 or greater,

        Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less than three times
        normal,

        Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

        Patients of both genders must be willing to practice effective birth control during this
        trial because the potential for teratogenic effects are unknown.

        Patients may have had prior adjuvant treatment with immunotherapy, including interferon, as
        long as 3 weeks have elapsed since prior systemic therapy.

        EXCLUSION CRITERIA:

        Patients will be excluded:

        Who have ocular or mucosal melanoma.

        Who are undergoing or have undergone in the past 3 weeks any systemic therapy except
        surgery for their cancer, and must have recovered to a grade I from any adverse effects of
        treatment prior to entry, other than those that do not have clinical implications, e.g.
        vitiligo, alopecia.

        Have active systemic infections, autoimmune disease or any known immunodeficiency disease.

        Who require systemic steroid therapy.

        Who are pregnant (because of possible side effects on the fetus) or breastfeeding because
        of unknown effects on the developing child).

        Who are known to be positive for hepatitis BsAG or human immunodeficiency virus (HIV)
        antibody (because of possible immune effects of these conditions).

        Who have any form of autoimmune disease (such as autoimmune colitis or Crohn's Disease) or
        immunodeficiency as evidenced by abnormal white blood count (WBC) count 8 and/or presence
        of opportunistic infections. Must have recovered immune competence after radiation therapy.
        (The experimental treatment being evaluated in this protocol depends on an intact immune
        system. Patients who have decreased immune competence may be less responsive to the
        experimental treatment and more susceptible to its toxicities.)

        Who have previously been immunized with gp100.

        Who have known hypersensitivity to any of the agents used in this study.

        Who have previously received chemotherapy for treatment of melanoma.