MAGE-A3/HPV 16 Vaccine for Squamous Cell Carcinoma of the Head and Neck
Recruitment status was Recruiting
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.
Squamous Cell Carcinoma of the Head and Neck
Biological: HPV-16 vaccine
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1 Open Label, Dose Escalation Study to Evaluate the Effect of Four Doses of MAGE-A3/HPV 16 Trojan Peptides 0001 and 0002 Administered Subcutaneously in Combination With Montanide and GM-CSF on Immunological Response, Safety, Tolerability, and Preliminary Efficacy in Patients With Squamous Cell Carcinoma of the Head and Neck|
- Toxicity: Maximum grade of each toxicity and percentage of patients experiencing toxicity. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
|Study Start Date:||November 2005|
|Estimated Study Completion Date:||December 2011|
|Estimated Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
Experimental: MAGE -A3 vaccine
for those individuals in which tumor tests positive for MAGE-A3
Three dose levels of MAGE-A3 vaccine will be tested : 500ug, 1000 ug and 1500 ug
Experimental: HPV 16 vaccine
for patients with HPV 16 positive tumor
Biological: HPV-16 vaccine
Three dose levels of HPV- 16 vaccine will be tested : 500ug, 1000 ug and 1500 ug
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00257738
|Contact: Scott E Strome, MDfirstname.lastname@example.org|
|United States, Maryland|
|University of Maryland School of Medicine||Recruiting|
|Baltimore, Maryland, United States, 21201-1619|
|Contact: Jennifer M DeSanto, RN 410-328-6215 email@example.com|
|Principal Investigator: Martin J. Edelman, MD|
|Principal Investigator:||Martin J. Edelman, MD||University of Maryland, Greenebaum Cancer Ctr|