NCT05317000

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: Barbara Burtness · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

This Phase 2 study is a 3-arm window trial, randomizing patients to pre-operative treatment with 5-azacytidine alone, to nivolumab alone, or the combination of 5-azacytidine and nivolumab. The primary endpoint is immune-related pathologic response, employing the quantitative immune-related pathologic response criteria (ir-PRC) of Cottrell et al. The secondary endpoint is augmentation of tumor infiltration of the tumor microenvironment as determined by a quantitative immunofluorescence score (QIF) measuring CD3+ lymphocytes and granzyme B expression. Secondary endpoints are objective response by modified RECIST, change in Ki-67, change in caspase activity, toxicity and hyperprogression. Patients are eligible with T1-3, N0-2, M0 p16-positive squamous cell carcinoma of the oropharynx deemed resectable by a surgical co-investigator. Patients must have normal absolute lymphocyte count, adequate end organ function, and not require full dose anticoagulation. Patients must be capable of providing, and provide, written informed consent. Patients on Arm A receive 5-azacytidine 75mg/m2 IV once daily day 1-5. Patients on Arm B receive nivolumab 240 mg IV days 1 and 15. Patients on Arm C receive 5-azacytidine as described above and receive nivolumab 240 mg IV days 2 and 16. On arms A and B surgery is performed during the period of days 16 to 18, and on Arm C during the period of days 17 to 18. The study will enroll 8 patients to 5-azacytidine monotherapy and 20 patients per arm to nivolumab or 5-azacytidine/nivolumab combination and has an 80% power to detect a significant difference in immune-related pathologic response, according to the criteria of Cottrell, between the combination arm and each of the monotherapy arms considered separately, using a one-sided Fisher's exact test at a significance level of 0.10.

Conditions

• Squamous Cell Carcinoma of Head and Neck

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2023-03-23
• Primary completion: 2028-06-30
• Completion: 2028-11-30
• First posted: 2022-04-07
• Last updated: 2026-01-12

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study