Combining 5-Azacytidine and Nivolumab for HPV-Associated Head and Neck Cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This Phase 2 clinical trial evaluates the effectiveness of 5-azacytidine, a chemotherapy drug, and nivolumab, an immunotherapy, in treating resectable HPV-associated squamous cell carcinoma of the head and neck. Patients will be randomized into three groups: one receiving 5-azacytidine alone, another receiving nivolumab alone, and a third receiving both treatments together. The study aims to assess immune-related pathologic responses and tumor infiltration in the microenvironment, with various secondary endpoints including toxicity and objective response rates. The trial is designed to determine if the combination therapy enhances treatment sensitivity compared to monotherapy.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. Patients with resectable squamous cell carcinoma of the oropharynx. Histologic or cytologic confirmation from either a biopsy/aspirate of the oropharyngeal primary lesion and/or a regional lymph node is required.
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 \> 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 \> 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. ECOG performance status 0 or 1.
8. Absolute neutrophil count (ANC) \> 1500/microliter, absolute lymphocyte count (ALC) \> 1000/microliter, hemoglobin \> 9 g/dl, platelets \> 100,000/microliter.
9. AST and ALT \< 2.5 x upper limit of normal. Bilirubin \< 1.5 x upper limit of normal.
10. Albumin \> 3.0 g/dl.
11. Creatinine \< 1.5 x upper limit of normal.
12. 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.
13. 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

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.

Where it's running

• Yale University
  New Haven, Connecticut, United States Recruiting

Study contacts

• Principal investigator: Barbara Burtness, MD — Yale University
• Study coordinator: Carole Ramm
• Email: carole.ramm@yale.edu
• Phone: (203) 785-4095

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.