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

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 testing if combining a chemotherapy drug and an immunotherapy can help people with HPV-related head and neck cancer do better than using either treatment alone.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Yale University (Academic / other)
• Drugs / interventions: nivolumab, radiation, chemotherapy, immunotherapy
• Locations: 1 site (New Haven, Connecticut)
• Trial ID: NCT05317000 on ClinicalTrials.gov

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.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 with resectable, p16-positive squamous cell carcinoma of the oropharynx.

Not a fit: Patients with non-resectable tumors or those who do not meet the HPV association criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes for patients with HPV-associated head and neck cancer.

How similar studies have performed: While the combination of these specific treatments is experimental, similar approaches in other studies have shown promise in enhancing immune responses in cancer treatment.

Eligibility criteria

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.

Where this trial is running

New Haven, Connecticut

• Yale University — New Haven, Connecticut, United States (Recruiting)

Study contacts

• Principal investigator: Barbara Burtness, MD — Yale University
• Study coordinator: Carole Ramm

Conditions Squamous Cell Carcinoma of Head and Neck; HPV- Associated Head and Neck Squamous Cell Cancer