RECRUITINGPhase 2INTERVENTIONAL

5-Azacytidine and/or Nivolumab in Resectable HPV-Associated HNSCC

A Window Trial of 5-Azacytidine or Nivolumab or Combination Nivolumab Plus 5-Azacytidine in Resectable HPV-Associated Head and Neck Squamous Cell Cancer

About This Trial

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.

Who May Be Eligible (Plain English)

Who May Qualify: 1. Patients with resectable diagnosed by tissue sample (biopsy-confirmed) squamous cell carcinoma of the oropharynx. 2. T1-T3, N0-N2, M0 stage by AJCC 8th edition for HPV-initiated oropharynx cancer. 3. Resectability confirmed by a surgical co-investigator; evaluation may include operative endoscopy to discover second primaries and map tumor extent with biopsy 4. 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 willing to sign a consent form for the Yale Biosample Repository Protocol are acceptable if they meet the volume requirements above. 5. HPV-association confirmed by institutional p16 testing (CINtec antibody demonstrating strong and diffuse nuclear and cytoplasmic staining in at least 70% of tumor cells). 6. Age \> or equal to 18 years. 5-azacytidine and nivolumab are tolerated in the elderly and there is no upper age limit for patients with adequate performance status. 7. Males and females are eligible. 8. You should be able to carry out daily activities with 0 level of ability (ECOG 0) or 1. 9. Absolute neutrophil count (ANC) \> or equal to 1500/microliter, absolute lymphocyte count (ALC) \> or equal to 1000/microliter, hemoglobin \> or equal to 9 g/dl, platelets \> or equal to 100,000/microliter. 10. AST and ALT \< 2.5 x upper limit of normal. Bilirubin \< 1.5 x upper limit of normal. 11. Albumin \> or equal to 3.0 g/dl. 12. Creatinine \< or equal to 1.5 x upper limit of normal. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: 1. Patients with resectable histologically or cytologically confirmed squamous cell carcinoma of the oropharynx. 2. T1-T3, N0-N2, M0 stage by AJCC 8th edition for HPV-initiated oropharynx cancer. 3. Resectability confirmed by a surgical co-investigator; evaluation may include operative endoscopy to discover second primaries and map tumor extent with biopsy 4. 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. 5. HPV-association confirmed by institutional p16 testing (CINtec antibody demonstrating strong and diffuse nuclear and cytoplasmic staining in at least 70% of tumor cells). 6. Age \> or equal to 18 years. 5-azacytidine and nivolumab are tolerated in the elderly and there is no upper age limit for patients with adequate performance status. 7. Males and females are eligible. 8. ECOG performance status 0 or 1. 9. Absolute neutrophil count (ANC) \> or equal to 1500/microliter, absolute lymphocyte count (ALC) \> or equal to 1000/microliter, hemoglobin \> or equal to 9 g/dl, platelets \> or equal to 100,000/microliter. 10. AST and ALT \< 2.5 x upper limit of normal. Bilirubin \< 1.5 x upper limit of normal. 11. Albumin \> or equal to 3.0 g/dl. 12. Creatinine \< or equal to 1.5 x upper limit of normal. 13. 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. 14. 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 4. Exclusion Criteria: 1. Medical contraindication to transoral surgery. 2. Full dose anticoagulation. 3. Concomitant invasive malignancy, or malignancy within 2 years except for hormonally responsive breast or prostate cancer, resected non-melanoma skin cancer, resected uterine cervical carcinoma or meningioma. 4. Inability to give informed consent. 5. Prior systemic therapy, radiation, or gross resection for the tumor under study. 6. Women may not be pregnant or breast-feeding. 7. Patients with active autoimmune disease, supraphysiologic systemic corticosteroid use within 7 days, and/or allergies/contraindications to the study drugs are excluded.

Treatments Being Tested

DRUG

Combination 5-azacytidine and nivolumab

The primary objective of the study is 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.

DRUG

5-azacytidine

Chemotherapy is the use of drugs to destroy cancer cells. It usually works by keeping the cancer cells from growing, dividing, and making more cells. Because cancer cells usually grow and divide faster than normal cells, chemotherapy has more of an effect on cancer cells. 5-azacytidine works by slowing down the growth of cancer cells. 5-azacytidine has been demonstrated to improve the cell's ability to make some proteins which signal to the immune system.

DRUG

Nivolumab

Immunotherapy is a type of treatment that uses your body's own immune system to help fight cancer. Specifically, Nivolumab belongs to a class of anti-cancer drugs known as immune checkpoint inhibitors. 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.

Locations (1)

Yale University

New Haven, Connecticut, United States