Vaccine Therapy in Treating Patients With Advanced Melanoma
Condition: Intraocular Melanoma; Malignant Conjunctival Neoplasm; Melanoma (Skin)
MeSH terms: Melanoma; Conjunctival Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Vaccine therapy may help the body build an effective immune response to kill tumor
      cells.

      PURPOSE: This randomized clinical trial is studying how well vaccine therapy works in
      treating patients with advanced melanoma.
    

Detailed description: 
      OBJECTIVES:

        -  To assess the circulating CD8 T-cell response to vaccination with a multipeptide vaccine
           in patients with advanced melanoma.

        -  To determine whether immunization with peptides and incomplete Freund's adjuvant induces
           lymph-node-like aggregates (LNLA) and tertiary lymphoid organs (TLOs) in the skin of
           these patients.

        -  To determine whether extended immunization (vaccinations 4-6) is associated with
           induction of negative immune-regulatory processes in the vaccination site
           microenvironment/TLO.

        -  To characterize peptide-reactive CD4 and CD8 T cells in loco at sites of immunization
           with a multipeptide vaccine.

        -  To characterize the expression of toll-like receptors 4, 7, 8, and 9, and MyD88 in
           dendritic cells infiltrating vaccination sites over the course of 6 vaccinations and
           after vaccination.

      OUTLINE: Patients are randomized to 1 of 10 arms.

      All patients receive primary vaccine comprising melanoma multipeptides and tetanus toxoid
      helper peptide emulsified in incomplete Freund's adjuvant, half of the volume subcutaneously
      (SC) and the other half intradermally (ID), 6 times over 7 weeks on days 1, 8, 15, 29, 36,
      and 43. Vaccines are administered in a single skin location on an extremity clinically
      uninvolved with melanoma. A replicate vaccine site is identified for each patient for skin
      biopsy with or with out replica vaccine administration.

        -  Arm 1A: Patients receive no replicate vaccine. Patients undergo surgical biopsy at
           replicate vaccine site on day 1.

        -  Arm 1B: Patients receive replicate vaccine comprising incomplete Freund's adjuvant only
           SC and ID on day 1 and undergo surgical biopsy at replicate vaccine site on day 8 (1
           week after replicate vaccine 1).

        -  Arm 1C: Patients receive replicate vaccine comprising incomplete Freund's adjuvant only
           SC and ID on days 1, 8, and 15 and undergo surgical biopsy at replicate vaccine site on
           day 22 (1 week after replicate vaccine 3).

        -  Arm 1D: Patients receive replicate vaccine comprising incomplete Freund's adjuvant only
           SC and ID on days 1, 8, 15, 29, 36, and 43 and undergo surgical biopsy at replicate
           vaccine site on day 50 (1 week after replicate vaccine 6). Patients are evaluated 1-3
           weeks after biopsy.

        -  Arm 1E: Patients receive replicate vaccine comprising incomplete Freund's adjuvant only
           SC and ID on days 1, 8, 15, 29, 36, and 43 and undergo surgical biopsy at replicate
           vaccine site on day 85 (6 week after replicate vaccine 6). Patients are evaluated 1-3
           weeks after biopsy.

        -  Arm 2A: Patients receive no replicate vaccine. Patients undergo surgical biopsy at
           replicate vaccine site on day 1.

        -  Arm 2B: Patients receive replicate vaccine (the same as primary vaccine) SC and ID on
           day 1 and undergo surgical biopsy at replicate vaccine site on day 8 (1 week after
           replicate vaccine 1).

        -  Arm 2C: Patients receive replicate vaccine (the same as primary vaccine) SC and ID on
           days 1, 8, and 15 and undergo surgical biopsy at replicate vaccine site on day 22 (1
           week after replicate vaccine 3).

        -  Arm 2D: Patients receive replicate vaccine (the same as primary vaccine) SC and ID on
           days 1, 8, 15, 29, 36, and 43 and undergo surgical biopsy at replicate vaccine site on
           day 50 (1 week after replicate vaccine 6). Patients are evaluated 1-3 weeks after
           biopsy.

        -  Arm 2E: Patients receive replicate vaccine (the same as primary vaccine) SC and ID on
           days 1, 8, 15, 29, 36, and 43 and undergo surgical biopsy at replicate vaccine site on
           day 85 (1 week after replicate vaccine 6). Patients are evaluated 1-3 weeks after
           biopsy.

      Tissue biopsies are examined by reverse transcriptase-PCR, IHC, protein analysis, flow
      cytometry, and western blot. Blood samples are collected periodically and examined by ELIspot
      assay, tetramer staining, and proliferation assay.

      After completion of study therapy, patients are followed annually.
    

Intervention name(s): incomplete Freund's adjuvant; multi-epitope melanoma peptide vaccine; tetanus toxoid helper peptide; biopsy
Intervention type(s): Biological; Biological; Biological; Procedure
Intervention description(s): Given subcutaneously and intradermally; Given subcutaneously and intradermally; Given subcutaneously and intradermally; Patients undergo surgical biopsy at replicate vaccine site
Intervention MeSH terms: Freund's Adjuvant
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage II melanoma; stage III melanoma; stage IV melanoma; ciliary body and choroid melanoma, medium/large size; ciliary body and choroid melanoma, small size; conjunctival melanoma; extraocular extension melanoma; iris melanoma; metastatic intraocular melanoma; recurrent intraocular melanoma