This phase II trial evaluates whether azacitidine (5-azacytidine) increases sensitivity to nivolumab in patients with human papillomavirus (HPV)-associated oropharyngeal cancer. Azacitidine is a chemotherapy drug that works by slowing down the growth of cancer cells. It has been shown to improve the cell’s ability to make some proteins which signal to the immune system. Nivolumab is a type of immunotherapy drug known as an immune checkpoint inhibitor. Cancer cells are able to “turn off” the immune system by increasing the production of a protein called PD-1. Nivolumab can block PD-1 and may be able to re-activate the immune response to kill head and neck cancer cells. Azacitidine may make HPV-associated oropharyngeal cancer cells more sensitive to treatment with nivolumab by altering the body's immune response, which may make treatment with nivolumab more effective than it would be on its own.
Additional locations may be listed on ClinicalTrials.gov for NCT05317000.
Locations matching your search criteria
United States
Connecticut
New Haven
Yale UniversityStatus: Active
Contact: Barbara Ann Burtness
Phone: 203-737-7636
Trumbull
Smilow Cancer Hospital Care Center-TrumbullStatus: Active
Contact: Barbara Ann Burtness
Phone: 203-737-7636
Waterford
Smilow Cancer Hospital Care Center - WaterfordStatus: Active
Contact: Barbara Ann Burtness
Phone: 203-737-7636
PRIMARY OBJECTIVE:
I. To determine whether exposure to the demethylating agent 5-azacytidine will sensitize HPV-associated oropharynx cancer to nivolumab by induction of interferon response, neoantigen expression, and augmentation of lymphocyte infiltration of the tumor microenvironment.
OUTLINE: Patients are randomized to 1 of 3 arms.
ARM A: Patients receive azacitidine intravenously (IV) once daily (QD) over 10-40 minutes on days 1-5 in the absence of disease progression or unacceptable toxicity. Patients undergo standard of care surgery between days 16 and 18. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) during screening and end of treatment on study. Patients undergo collection of blood samples throughout the study and may undergo biopsy at screening.
ARM B: Patients receive nivolumab IV QD over 30 minutes on days 1 and 15 in the absence of disease progression or unacceptable toxicity. Patients undergo standard of care surgery between days 16 and 18. Patients also undergo CT or MRI during screening and end of treatment on study. Patients undergo collection of blood samples throughout the study and may undergo biopsy at screening.
ARM C: Patients receive azacitidine IV QD over 10-40 minutes on days 1-5 and nivolumab IV QD over 30 minutes on days 2 and 16 in the absence of disease progression or unacceptable toxicity. Patients undergo standard of care surgery between days 17 and 18. Patients also undergo CT or MRI during screening and end of treatment on study. Patients undergo collection of blood samples throughout the study and may undergo biopsy at screening.
After completion of study treatment, patients are followed up at 30 and 90 days following surgery.
Lead OrganizationYale University
Principal InvestigatorBarbara Ann Burtness
