A Window Trial of 5-Azacytidine or Nivolumab or Combination Nivolumab Plus 5-Azacytidine in Resectable HPV-Associated Head and Neck Squamous Cell Cancer
This study is being done because both 5-azacytidine and nivolumab can influence the immune system's response to HPV-associated head and neck cancer, and we wish to evaluate whether taking 5-azacytidine will make HPV-associated head and neck cancer more sensitive to treatment with nivolumab. 5-Azacytidine (5-AZA) is a chemotherapy, and nivolumab is an immunotherapy. Both drugs are approved for use in the US by the Food and Drug Administration (FDA) for use in the treatment of different types of cancer, and nivolumab is approved for use in head and neck cancer that has previously been treated with chemotherapy. Because they are not approved to be used together in HPV-associated head and neck cancer, these drugs are considered experimental in this study. For this study, the drugs will be used either together or separately.
• Patients with resectable histologically or cytologically confirmed squamous cell carcinoma of the oropharynx.
• T1-T3, N0-N2, M0 stage by AJCC 8th edition for HPV-initiated oropharynx cancer.
• Resectability confirmed by a surgical co-investigator; evaluation may include operative endoscopy to discover second primaries and map tumor extent with biopsy
• In addition to diagnostic biopsies, biopsies in clinic or at the time of operative endoscopy are required to yield primary tumor for research purposes equivalent to or greater than 3mm cup forceps biopsies X 3. Prior biopsies for research obtained with informed consent for the Yale Biosample Repository Protocol are acceptable if they meet the volume requirements above.
• HPV-association confirmed by institutional p16 testing (CINtec antibody demonstrating strong and diffuse nuclear and cytoplasmic staining in at least 70% of tumor cells).
• Age \> 18 years. 5-azacytidine and nivolumab are tolerated in the elderly and there is no upper age limit for patients with adequate performance status.
• Males and females are eligible.
• ECOG performance status 0 or 1.
• Absolute neutrophil count (ANC) \> 1500/microliter, absolute lymphocyte count (ALC) \> 1000/microliter, hemoglobin \> 9 g/dl, platelets \> 100,000/microliter.
⁃ AST and ALT \< 2.5 x upper limit of normal. Bilirubin \< 1.5 x upper limit of normal.
⁃ Albumin \> 3.0 g/dl.
⁃ Creatinine \< 1.5 x upper limit of normal.
⁃ Women of child-bearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of study treatment. An extension up to 72 hours prior to the start of study treatment is permissible in situations where results cannot be obtained within the standard 24-hour window.
⁃ Willing and able to provide written informed consent. Informed consent is required prior to research-related activities, including biopsy. However, if written informed consent for participation in the biosample repository protocol has been obtained, tissue obtained under that consent can be used to meet eligibility criterion 6.1.4.