MAGE-A3/HPV 16 Vaccine for Squamous Cell Carcinoma of the Head and Neck - Full Text View

Sponsored by:	National Institute of Dental and Craniofacial Research (NIDCR)
Information provided by:	National Institute of Dental and Craniofacial Research (NIDCR)
ClinicalTrials.gov Identifier:	NCT00257738

Purpose

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.

Condition	Intervention	Phase
Squamous Cell Carcinoma of the Head and Neck	Biological: MAGE-A3 and HPV 16 Trojan peptides	Phase I

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Dose Comparison, Single Group Assignment, Safety/Efficacy Study
Official Title:	MAGE-A3/HPV 16 Peptide Based Immunotherapeutic Vaccines for Squamous Cell Carcinoma of the Head and Neck

Further study details as provided by National Institute of Dental and Craniofacial Research (NIDCR):

Primary Outcome Measures:

Toxicity: Maximum grade of each toxicity and percentage of patients experiencing toxicity. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment:	90
Study Start Date:	November 2005
Estimated Study Completion Date:	November 2008
Estimated Primary Completion Date:	September 2008 (Final data collection date for primary outcome measure)

Intervention Details:

Mage-A3

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 prevalance of MAGE-A3 and HPV 16 on SCCHN, and characterized several putative cytolytic and helper epitopes. Addtionally, 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 feasability 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 reponse 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.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Biopsy-proven progressive, recurrent or metastatic Squamous Cell Carcinoma of the Head and Neck.
Biopsy-proven Squamous Cell Carcinoma of the Head and Neck which the patient is unwilling to have treated with surgery, chemotherapy or radiation therapy.
Age greater than or equal to 18 - 80 years of age.
ALL of the following: HLA-A2 positive tumor and HLA-A2 positive peripheral blood lymphocytes.
One or more of the following: MAGE-A3 positive tumor HPV 16 positive tumor or both.
Laboratory values: Alkaline Phosphastase of less than or equal to 3 times the upper limit of normal, AST less than or equal to 3 times the upper limit of normal, Creatinine less than or equal to 1.5 times the upper limit or normal, and Hemoglobin greater tha or equal to 9.0 mg/dL.
Patients must be capable of understanding the investigational nature of this study, the potential risks and benefits, and capable of providing valid informed consent.
The subject must be willing to return to the University of Maryland Medical Center for treatment and study-related follow up procedures and testing.
Life expectance of greater than or equal to 7 months.
Willingness to provide blood and tumor specimens and complete the imaging studies as required by the protocol.
A tumor that is biopsy accessible.

Exclusion Criteria:

ECOG performance status of 3 or 4.
ANY of the following: Known H.I.V. infection; other circumstances that in the opinion of the study physician renders the patient a poor candidate for this trial (e.g. concurrent use of systemic immunosuppressants or an immunocompromising condition).Patients with ANY malignant or metastatic Squamous Cell Carcinoma mass or lesion with the Central Nervous System [CNS] (e.g. Intraparenchymal- brain, Intracordal/Spinal Canal, Bony masses or lesions with extension into the CNS. AND Patients with ANY malignant or metastatic mass or lesion, or volume of a mass or lesion in a location that in the judgement of the Investigator, may significantly impair the health of or threaten the patients' life should an inflammatory response occur.
Any of the following: Pregnant women; Nursing women unwilling to stop breastfeeding; men or women of childbearing potential who are unwilling to employ adequate contraception.
Any of the following prior therapies: Chemotherapy less than or equal to 4 weeks prior to registration; Immunotherapy less than or equal to 4 weeks prior to registration; Radiation Therapy less than or equal to 4 weeks prior to registration; Biologic therapy less than or equal to 4 weeks prior to registration; Immunotherapy less than oe equal to 4 weeks prior to registration.
Other concurrent chemotherapy, immunotherapy, radiotherapy or any ancillary treatment considered investigational.
Either of the following: Other active cancer requiring therapy to control the disease; A history of other malignancy less than or equal to 3 years (except for adequately treated basal cell carcinoma and squamous cell carcinoma of the skin, prostate cancer or carcinoma of the cervix).
Pre-treatment Hemoglobin of less than or equal to 9 mg/dL.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00257738

Contacts

Contact: Scott E Strome, MD

410-328-5828

sstrome@smail.umaryland.edu

Locations

United States, Maryland
University of Maryland School of Medicine	Recruiting
Baltimore, Maryland, United States, 21201-1619
Contact: Scott E Strome, MD 410-328-5828 sstrome@smail.umaryland.edu
Principal Investigator: Scott E Strome, MD

Sponsors and Collaborators

National Institute of Dental and Craniofacial Research (NIDCR)

Investigators

Principal Investigator:

Scott E Strome, MD

University of Maryland School of Medicine

More Information

Responsible Party:	University of Maryland School of Medicine ( Scott E Strome, MD )
Study ID Numbers:	NIDCR-15324
Study First Received:	November 21, 2005
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00257738
Health Authority:	United States: Federal Government

Study placed in the following topic categories:

Epidermoid carcinoma
Squamous cell carcinoma
Carcinoma, squamous cell
Neoplasms, Squamous Cell

Carcinoma, Squamous Cell
Carcinoma, squamous cell of head and neck
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on January 13, 2009