Tumor and Vaccine Site With a Toll Like Receptor (TLR) Agonist
Condition: Melanoma
MeSH terms: Melanoma
Intervention: gp100; R848 gel; MAGE-3
Intervention description: 1 ml of gp100 peptide vaccine: 0.5 ml administered intradermally and the other 0.5 ml subcutaneously in the same extremity weekly (every 7 days +/- 2 days) for 8 weeks.; Applied to the gp100 vaccine injection site immediately following the injection, allowed to air dry for 30 minutes then covered with gauze dressing.; 1 ml of MAGE-3 peptide vaccine: 0.5 ml administered intradermally and the other 0.5 ml subcutaneously in the same extremity weekly (every 7 days +/- 2 days) for 8 weeks.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Enrollment: 47.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: gp100 peptide; MAGE-3 peptide; R848; Resiquimod; Toll Like Receptor; TLR; T-cells; Tumor; Metastatic; Lesions; Injection Site

Summary:

      The goal of this clinical research study is to learn if the vaccines, gp100(g209-2M), and
      MAGE-3, when given in combination with resiquimod (R848), can help to stimulate the immune
      system against melanoma.
    

Eligibility criteria:

        Inclusion Criteria:

          1. HLA-A*0201 positive (to enable immunization with the HLA class I restricted
             gp100(g209-2M) peptide). Stage IIB or IIC patients will be enrolled after review and
             approval by the PI. (a tool to determine the projected survival at 5 years, like, but
             not limited to, the nomogram at www.melanomaprognosis.org. If the projected survival
             is less than 50% at 5 years, then the patient is considered for enrollment. This is
             with the recognition that the adjuvant, if effective offers a significant impact in
             that group of stage II patients.)

          2. Patients >/= 18 years old with histologically documented metastatic melanoma with a.
             (Metastatic disease cohort) Measurable disease, stage IIIB, IIIC (in transit lesions
             with or without nodal metastases) that includes lesions accessible for biopsies or IV
             M1B b. (Adjuvant cohort) subjects who are NED and stage III or IV. This includes
             patients with stage IV disease resected to NED. Stage IIB or IIC patients will be
             enrolled after review and approval by the PI.

          3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

          4. At least 2 biopsiable easily accessible cutaneous and subcutaneous lesions in patients
             in the metastatic disease cohort

          5. White Blood Count (WBC) >/= 3000/mm^3 (part 1 & 2)

          6. Platelet count >/= 90,000/mm^3 (part 1 & 2)

          7. Serum alanine aminotransferase (ALT) and Aspartate Aminotransferase (AST) </= 3 X
             upper limit of normal (ULN) (part 1 & 2)

          8. Total bilirubin </= 2 X ULN, except for patients with Gilbert's syndrome who must have
             a total bilirubin less than 3.0 mg/dl Total bilirubin </= 2 X ULN, except for patients
             with Gilbert's syndrome who must have a total bilirubin less than 3.0 mg/dl (part 1 &
             2)

          9. Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental
             treatment being evaluated in this protocol depends on an intact immune system.
             Patients who are HIV seropositive can have decreased immune competence and thus may be
             less responsive to the experimental treatment and more susceptible to its toxicities.)

         10. Negative pregnancy test for women of childbearing potential (WOCBP) A WOCBP has not
             undergone a hysterectomy or who has not been naturally postmenopausal for at least 12
             consecutive months (i.e., who has had menses at any time in the preceding 12
             consecutive months)

         11. Patients of both gender must practice a barrier method of birth control while
             participating in this trial.

        Exclusion Criteria:

          1. Active autoimmune disease requiring active therapy with any form of steroid or
             immunosuppressive therapy or a documented history of any of the following:
             inflammatory bowel disease; regional enteritis; systemic lupus erythematosis;
             Sjogren's syndrome; inflammatory neurologic disorder such as multiple sclerosis; or
             any immune mediated disease that can cause life-threatening symptoms or severe
             organ/tissue damage in the opinion of the principle investigator.

          2. Concurrent systemic or inhaled steroid therapy

          3. Any form of active primary or secondary immunodeficiency

          4. Prior malignancy except for the following: adequately treated basal cell or squamous
             cell skin cancer, in-situ cervical cancer, thyroid cancer (except anaplastic) or any
             cancer from which the patient has been disease-free for 2 years

          5. History of immunization with gp100(g209-2M)

          6. Active systemic infections requiring intravenous antibiotics

          7. Women who are breastfeeding

          8. Prior systemic therapy, radiation therapy or intracavitary surgery (intra-thoracic,
             intra-abdominal or intracranial) within 28 days of starting study treatment.

          9. Patients on chronic anticoagulation such as Aspirin, Plavix, or Coumadin who cannot
             have anticoagulation held for procedures are not eligible due to the need for
             leukapheresis