NCT06997094

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

Phase I Decitabine Dose-Tolerance in Surgically Resectable HPV-Negative Head and Neck Cancer

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: Mayo Clinic · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial tests the safety, side effects, and best dose of decitabine in combination with standard of care surgery, radiation, and/or chemotherapy and the effectiveness of the combination in treating patients with head and neck squamous cell cancers that are not caused by human papilloma virus (HPV-negative) and that can be removed by surgery (resectable). Decitabine, an antimetabolite, stops cells from making deoxyribonucleic acid (DNA) and may kill tumor cells. Studies have shown that medications like decitabine can make some types of solid tumors more sensitive to chemotherapy. This allows the chemotherapy to be more effective, with slower progression and longer survival. Decitabine is also a clinically active demethylating agent, and may help make tumor cells more sensitive to radiation therapy. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. External beam radiation therapy (EBRT) is a type of radiation that uses a machine to aim high-energy rays at the tumor from outside the body. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving decitabine in combination with standard of care surgery, radiation and/or chemotherapy may be safe, tolerable, and/or effective in treating patients with surgically resectable HPV-negative head and neck squamous cell cancers.

Detailed 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.

Conditions

• Human Papillomavirus-Negative Neck Squamous Cell Carcinoma
• Resectable Head and Neck Squamous Cell Carcinoma
• Resectable Human Papillomavirus-Independent Head and Neck Mucosal Squamous Cell Carcinoma
• HPV-Negative Squamous Cell Carcinoma
• Resectable Head and Neck Squamous-cell Carcinoma

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
DRUG	Chemotherapy	Given concurrent chemotherapy
DRUG	Decitabine	Given IV
RADIATION	External Beam Radiation Therapy	Undergo EBRT
OTHER	Questionnaire Administration	Ancillary studies
PROCEDURE	Surgical Procedure	Undergo standard of care surgery

Timeline

• Start date: 2026-01-23
• Primary completion: 2027-11-08
• Completion: 2027-11-08
• First posted: 2025-05-30
• Last updated: 2026-01-26

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study