Decitabine in Combination With Standard of Care Therapy for the Treatment of Surgically Resectable HPV-Negative Head and Neck Cancer

Description

PRIMARY OBJECTIVE:

I. To prospectively evaluate the maximum tolerated dose (MTD) of decitabine, in both the preoperative and adjuvant phases of treatment, combined with standard-of-care therapy including surgery +/- chemoradiation for HPV-negative head and neck cancers.

SECONDARY OBJECTIVES:

I. Evaluation of acute (early onset) toxicities. (Stratified by methylation status) II. Evaluation of late onset toxicities. (Stratified by methylation status) III. Evaluation of event-free survival (EFS). (Stratified by methylation status) IV. Evaluation of overall survival (OS). (Stratified by methylation status) V. Evaluation of quality of life (QOL). (Stratified by methylation status)

CORRELATIVE RESEARCH OBJECTIVES:

I. In vivo methylation response to preoperative decitabine. II. Pharmacokinetics of decitabine. III. Exploratory circulating biomarkers.

OUTLINE: This is a dose-escalation study followed by a dose-expansion study.

PREOPERATIVE PHASE: Patients receive decitabine intravenously (IV) over 1 hour once daily (QD) for 3 days and undergo standard of care surgery within 28 days of receiving decitabine.

ADJUVANT TREATMENT: Patients receive decitabine IV over 1 hour QD for 3 days every 3 weeks during radiation therapy in the absence of disease progression or unacceptable toxicity. Patients also undergo EBRT QD on 5 days per week for up to 5-35 treatments per standard of care. Patients may receive concurrent chemotherapy of choice per standard of care.

Patients also undergo blood sample collection throughout the study.

After completion of study treatment, patients are followed up at 30 days, every 4-6 months for 2 years and then every 12 months for up to 5 years.