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

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.

NCT Number	NCT06997094
Lead Sponsor	Mayo Clinic
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
Enrollment	32 participants
Start Date	2026-01-23
Primary Completion	2027-11-08 (estimated)
Study Completion	2027-11-08 (estimated)
Updated on ClinicalTrials.gov	2026-07-15