5-Azacytidine and/or Nivolumab in Resectable HPV-Associated HNSCC
NCT ID: NCT05317000
Last Updated: 2025-11-14
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE2
50 participants
INTERVENTIONAL
2023-03-23
2028-09-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Arm A: 5-azacytidine
Patients will receive 5-azacytidine 75mg/m2 IV daily x 5. Treatment must begin on a Monday.
Patients will receive anti-emetic premedication with prochlorperazine 10 mg IV, a 5HT3 antagonist per institutional guidelines, aprepitant or fos-aprepitant, and prn lorazepam on day 1. Day 2-5 patients will receive prochlorperazine 10 mg IV. Subsequent day 5HT3 antagonist therapy will be determined per institutional guidelines, as recommendations vary based on the half-life of the agent chosen. PRN lorazepam can be used days 2-5.
Dexamethasone will be reserved for patients who are not controlled by the initial regimen.
A single cycle of 5-azacytidine will be administered and the patient scheduled for surgery in the period of day 16 through day 18.
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.
Arm B: Nivolumab
Nivolumab will be administered at a dose of 240 mg IV day 1 and day 15. Treatment must be given on a Monday or Tuesday.
No premedication will be given. Patients will be observed following the initial dose of nivolumab per institutional Surgery will be scheduled in the period of day 16 through day 18.
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.
Arm C: Combination 5-azacytidine and Nivolumab
Patients will receive 5-azacytidine 75mg/m2 IV daily x 5. Treatment must begin on a Monday. 5-azacytidine will be given prior to nivolumab on day 2.
Patients will receive anti-emetic premedication with prochlorperazine 10 mg IV, a 5HT3 antagonist per institutional guidelines, aprepitant or fos-aprepitant, and prn lorazepam on day 1. Day 2-5 patients will receive prochlorperazine 10 mg IV. Subsequent day 5HT3 antagonist therapy will be determined per institutional guidelines, as recommendations vary based on the half-life of the agent chosen. PRN lorazepam can be used days 2-5.
Nivolumab will be administered at a dose of 240 mg IV day 2 and day 16. No additional premedication will be given on day 16. Dexamethasone will be reserved for patients whose nausea and/or emesis is not controlled by the initial regimen. Surgery will be scheduled in the period of day 17 through day 18.
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.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
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.
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.
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.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
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 \> 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) \> 1500/microliter, absolute lymphocyte count (ALC) \> 1000/microliter, hemoglobin \> 9 g/dl, platelets \> 100,000/microliter.
10. AST and ALT \< 2.5 x upper limit of normal. Bilirubin \< 1.5 x upper limit of normal.
11. Albumin \> 3.0 g/dl.
12. Creatinine \< 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 6.1.4.
Exclusion Criteria
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.
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Institute of Dental and Craniofacial Research (NIDCR)
NIH
Barbara Burtness
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Barbara Burtness
Professor of Medicine, Medical Oncology
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Barbara Burtness, MD
Role: PRINCIPAL_INVESTIGATOR
Yale University
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Yale University
New Haven, Connecticut, United States
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Sharon Huie
Role: primary
Barbara Burtness, MD
Role: backup
References
Explore related publications, articles, or registry entries linked to this study.
Smith TW, Aberger EW, Follick MJ, Ahern DK. Cognitive distortion and psychological distress in chronic low back pain. J Consult Clin Psychol. 1986 Aug;54(4):573-5. doi: 10.1037//0022-006x.54.4.573. No abstract available.
Rosol Z. [Etiology and propagation of myocardial irritation]. Cas Lek Cesk. 1971 Jul 23;110(30):717. No abstract available. Czech.
Cohen EEW, Soulieres D, Le Tourneau C, Dinis J, Licitra L, Ahn MJ, Soria A, Machiels JP, Mach N, Mehra R, Burtness B, Zhang P, Cheng J, Swaby RF, Harrington KJ; KEYNOTE-040 investigators. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet. 2019 Jan 12;393(10167):156-167. doi: 10.1016/S0140-6736(18)31999-8. Epub 2018 Nov 30.
Burtness B, Harrington KJ, Greil R, Soulieres D, Tahara M, de Castro G Jr, Psyrri A, Baste N, Neupane P, Bratland A, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak WZ, Hong RL, Gonzalez Mendoza R, Roy A, Zhang Y, Gumuscu B, Cheng JD, Jin F, Rischin D; KEYNOTE-048 Investigators. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019 Nov 23;394(10212):1915-1928. doi: 10.1016/S0140-6736(19)32591-7. Epub 2019 Nov 1.
Vos JL, Elbers JBW, Krijgsman O, Traets JJH, Qiao X, van der Leun AM, Lubeck Y, Seignette IM, Smit LA, Willems SM, van den Brekel MWM, Dirven R, Baris Karakullukcu M, Karssemakers L, Klop WMC, Lohuis PJFM, Schreuder WH, Smeele LE, van der Velden LA, Bing Tan I, Onderwater S, Jasperse B, Vogel WV, Al-Mamgani A, Keijser A, van der Noort V, Broeks A, Hooijberg E, Peeper DS, Schumacher TN, Blank CU, de Boer JP, Haanen JBAG, Zuur CL. Neoadjuvant immunotherapy with nivolumab and ipilimumab induces major pathological responses in patients with head and neck squamous cell carcinoma. Nat Commun. 2021 Dec 22;12(1):7348. doi: 10.1038/s41467-021-26472-9.
Stewart RW. Cardiac transplantation at the Cleveland Clinic Foundation--the first 10 years. Clin Transpl. 1994:127-31.
Eklund AE, Eriksson G, Kallings LO, Liden S, Zetterquist S. [Venous leg ulcer, diagnosis and treatment]. Lakartidningen. 1980 Oct 1;77(40):3495-504. No abstract available. Swedish.
Bernstein RK. R-R interval studies: a simple office protocol for evaluation of autonomic neuropathy. Diabetes Care. 1984 Sep-Oct;7(5):510-3. doi: 10.2337/diacare.7.5.510b. No abstract available.
Gemzell C, Carlborl, Johansson ED, Roos P. Treatment of primary amenorrhoea with human pituitary and chorionic gonadotrophins. J Obstet Gynaecol Br Commonw. 1970 Jan;77(1):58-64. doi: 10.1111/j.1471-0528.1970.tb03408.x. No abstract available.
Albro PW, Fishbein L. Determination of prostaglandins by gas-liquid chromatography. J Chromatogr. 1969 Nov 11;44(3):443-51. doi: 10.1016/s0021-9673(01)92568-3. No abstract available.
Biktasova A, Hajek M, Sewell A, Gary C, Bellinger G, Deshpande HA, Bhatia A, Burtness B, Judson B, Mehra S, Yarbrough WG, Issaeva N. Demethylation Therapy as a Targeted Treatment for Human Papillomavirus-Associated Head and Neck Cancer. Clin Cancer Res. 2017 Dec 1;23(23):7276-7287. doi: 10.1158/1078-0432.CCR-17-1438. Epub 2017 Sep 15.
Kirst HA, Creemer LC, Paschal JW, Preston DA, Alborn WE Jr, Counter FT, Amos JG, Clemens RL, Sullivan KA, Greene JM. Antimicrobial characterization and interrelationships of dirithromycin and epidirithromycin. Antimicrob Agents Chemother. 1995 Jul;39(7):1436-41. doi: 10.1128/AAC.39.7.1436.
Davidovskii LIa. [Deficiency and transmembrane transport of water in pneumonia in young children]. Pediatriia. 1984 Mar;(3):54-5. No abstract available. Russian.
Glimelius B, Lahn M. Window-of-opportunity trials to evaluate clinical activity of new molecular entities in oncology. Ann Oncol. 2011 Aug;22(8):1717-25. doi: 10.1093/annonc/mdq622. Epub 2011 Jan 13.
Voillemin. [Urinary problems of paraplegics]. Rev Infirm. 1984 May;34(9):33-8. No abstract available. French.
Levy BP, Giaccone G, Besse B, Felip E, Garassino MC, Domine Gomez M, Garrido P, Piperdi B, Ponce-Aix S, Menezes D, MacBeth KJ, Risueno A, Slepetis R, Wu X, Fandi A, Paz-Ares L. Randomised phase 2 study of pembrolizumab plus CC-486 versus pembrolizumab plus placebo in patients with previously treated advanced non-small cell lung cancer. Eur J Cancer. 2019 Feb;108:120-128. doi: 10.1016/j.ejca.2018.11.028. Epub 2019 Jan 14.
Shapovalov AI, Shiriaev BI. [Synaptic interaction of individual motor neurons of the isolated frog spinal cord]. Neirofiziologiia. 1984;16(5):619-30. Russian.
Stansfeld CE, Wallis DI. Generation of an unusual depolarizing response in rabbit primary afferent neurones in the absence of divalent cations. J Physiol. 1984 Jul;352:49-72. doi: 10.1113/jphysiol.1984.sp015277.
Dendinger S, Brill WJ. Effect of the proline analogue baikiain on proline metabolism in Salmonella typhimurium. J Bacteriol. 1972 Dec;112(3):1134-41. doi: 10.1128/jb.112.3.1134-1141.1972.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2000025632
Identifier Type: -
Identifier Source: org_study_id