0804 GCC: MAGE-A3/HPV 16 Vaccine for Squamous Cell Carcinoma of the Head and Neck
Condition: Squamous Cell Carcinoma of the Head and Neck
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
Study type: Interventional
Phase: Phase 1

Summary: 
      Squamous Cell Carcinoma of the Head and Neck (SCCHN) is a devastating illness, the treatment
      of which is associated with significant morbidity. This type of cancer affects 43,000
      individuals each year with an estimated survival rate of 50%. A potential treatment
      alternative for this patient population is the use of peptide-based immunotherapy. This
      clinical tial will be using a vaccines comprised on the Trojan peptides MAGE-A3 and HPV 16 to
      treat patients with Squamous Cell Carcinoma of the Head and Neck who have recurrent,
      progressive or metastatic SCCHN.
    

Detailed description: 
      Squamous Cell Carcinoma of the Head and Neck affects 43,000 individuals in the United States
      annually with an estimated overall survival rate of 50%. In order to improve both the
      survival rate and quality of life for patients who develop unresectable disease recurrence,
      new therapeutic alternatives are mandated. One potential treatment alternative for this
      patient population is the use of peptide-based immunotherapy. Despite the success fo
      preclinical studies using peptide vaccines, therapeutic responses in patients have been
      sporadic. The reasons for failure are multifactorial and include problems with patient
      selection, a limited number of antigenic targets, and an inability to correlate immunologic
      response with therapeutic efficacy. Specifically, patients with disseminated SCCHN have
      defects in antigen processing, presentation and effector mechanisms that limit their ability
      to respond to T cell based immunotherapy. Additionally, a paucity of antigenic peptide
      epitopes are defined for SCCHN, and immunologic monitoring does not correlate well with
      clinical response.

      Recently several investigators, including our research team, have identified a high
      prevalence of MAGE-A3 and HPV 16 on SCCHN, and characterized several putative cytolytic and
      helper epitopes. Additionally, we have defined a novel method to enhance the immune response
      to therapeutic peptide vaccines using Trojan complexes composed of CD4 and CD8 T-cell
      epitopes, connected by furin cleavable linkers.

      In order to define the feasibility and safety of these agents in combination with GM-CSF and
      montanide ISA 51 for the immunotherapy of SCCHN, in this proposed trial, we will screen
      patients for immunologic competence based on specific eligibility criteria including both
      antigen and HLA-A2 expression on tumors. In registered patients, we will test the ability of
      two novel Trojan peptide complexes, composed of MAGE-A3 and human papilloma virus 16 (HPV 16)
      epitopes, to stimulate antigen-specific CD 4 and CD 8 T-cell responses. Finally, we will
      correlate immunologic response with cell dose and the generation of both HPV 16 and MAGE-A3
      antigen loss and HLA-A2 loss variants on tumors by evaluating patients for: 1) Changes in
      tumor size by both physical measurement and CT plus PET measurement; 2) Determining what
      proportions of individuals who achieve a complete response (CR), partial response (PR), or
      have stable disease (SD); 3) Progression-free survival; 4) Survival. Successful completion of
      this clinical trial will result in the development of a strong foundation for a Phase II/III
      clinical trial using HPV 16 and MAGE-A3 Trojan peptides for the immunotherapy of SCCHN.
    

Intervention name(s): MAGE-A3; HPV-16 vaccine
Intervention type(s): Biological; Biological
Intervention description(s): Three dose levels of MAGE-A3 vaccine will be tested : 500ug, 1000 ug and 1500 ug; Three dose levels of HPV- 16 vaccine will be tested : 500ug, 1000 ug and 1500 ug
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment