Decitabine in Combination With Standard of Care Therapy for the Treatment of Surgically Resectable HPV-Negative Head and Neck Cancer

NCT06997094 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: MC240706NCI-2025-0353724-012507
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial tests the safety, side effects, and best dose of decitabine in combination with standard of care surgery, radiation, and/or chemotherapy and the effectiveness of the combination in treating patients with head and neck squamous cell cancers that are not caused by human papilloma virus (HPV-negative) and that can be removed by surgery (resectable). Decitabine, an antimetabolite, stops cells from making deoxyribonucleic acid (DNA) and may kill tumor cells. Studies have shown that medications like decitabine can make some types of solid tumors more sensitive to chemotherapy. This allows the chemotherapy to be more effective, with slower progression and longer survival. Decitabine is also a clinically active demethylating agent, and may help make tumor cells more sensitive to radiation therapy. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. External beam radiation therapy (EBRT) is a type of radiation that uses a machine to aim high-energy rays at the tumor from outside the body. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving decitabine in combination with standard of care surgery, radiation and/or chemotherapy may be safe, tolerable, and/or effective in treating patients with surgically resectable HPV-negative head and neck squamous cell cancers.

Conditions

Human Papillomavirus-Negative Neck Squamous Cell Carcinoma; Resectable Head and Neck Squamous Cell Carcinoma; Resectable Human Papillomavirus-Independent Head and Neck Mucosal Squamous Cell Carcinoma; HPV-Negative Squamous Cell Carcinoma; Resectable Head and Neck Squamous-cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) of preoperative decitabine

  MTD will be selected based on the rate of grade 4 toxicity and correlative methylation response data.

  From first dose of preoperative decitabine to the first dose of adjuvant decitabine

• MTD of adjuvant decitabine

  MTD will be selected based on the rate of grade 4 toxicity and correlative methylation response data.

  From first dose of adjuvant decitabine to 28 days after the end of treatment

Secondary Outcomes (5)

• Incidence of acute (early onset) adverse events

  Up to 90 days

• Incidence of late onset adverse events

  From 91 days to 2 years

• Event-free survival

  1 year, 2 years, 5 years

• Overall survival

  1 year, 2 years, 5 years

• Quality of Life - EORTC QLQ-H&N35

  Baseline, at end of treatment, every 4-6 months post end of treatment for up to 2 years

Study Arms (1)

Treatment (decitabine, surgery, radiation)

EXPERIMENTAL

PREOPERATIVE PHASE: Patients receive decitabine IV over 1 hour QD for 3 days and undergo standard of care surgery within 28 days of receiving decitabine. ADJUVANT TREATMENT: Patients receive decitabine IV over 1 hour QD for 3 days every 3 weeks during radiation therapy in the absence of disease progression or unacceptable toxicity. Patients also undergo EBRT QD on 5 days per week for up to 5-35 treatments per standard of care. Patients may receive concurrent chemotherapy of choice per standard of care. Patients also undergo blood sample collection throughout the study.

Procedure: Biospecimen Collection; Drug: Chemotherapy; Drug: Decitabine; Radiation: External Beam Radiation Therapy; Other: Questionnaire Administration; Procedure: Surgical Procedure

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (decitabine, surgery, radiation)

Chemotherapy DRUG

Given concurrent chemotherapy

Also known as: Chemo, Chemotherapy (NOS), Chemotherapy, Cancer, General

Treatment (decitabine, surgery, radiation)

Decitabine DRUG

Given IV

Also known as: 5-Aza-2'-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine

Treatment (decitabine, surgery, radiation)

External Beam Radiation Therapy RADIATION

Undergo EBRT

Also known as: Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam Radiotherapy, External Beam Radiotherapy (conventional), External Beam RT, external radiation, External Radiation Therapy, external-beam radiation, Radiation, External Beam, Teleradiotherapy, Teletherapy, Teletherapy Radiation

Treatment (decitabine, surgery, radiation)

Questionnaire Administration OTHER

Ancillary studies

Treatment (decitabine, surgery, radiation)

Surgical Procedure PROCEDURE

Undergo standard of care surgery

Also known as: Operation, Surgery, Surgery Type, Surgery, NOS, Surgical, Surgical Intervention, Surgical Interventions, Surgical Procedures, Type of Surgery

Treatment (decitabine, surgery, radiation)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• REGISTRATION: Age ≥ 18 years
• REGISTRATION: Histologic confirmation of HPV-negative, squamous cell carcinoma of the head and neck that is surgically resectable. HPV-status confirmation by p16, circulating tumor DNA or in-situ hybridization is only required for oropharyngeal primaries
• Includes mucosal and non-mucosal subsites
• Includes head and neck of unknown primary origin REGISTRATION: Measurable disease preoperatively, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or equivalent criteria
• NOTE: Tumor lesions in a previously irradiated area are not considered measurable disease; disease that is measurable by physical examination only is not eligible
• REGISTRATION: Absence of distant metastases on standard diagnostic work-up ≤ 16 weeks prior to registration. (chest computed tomography \[CT\] or positron emission tomography \[PET\]/CT)
• REGISTRATION: Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only
• NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• REGISTRATION: Hemoglobin ≤ 9.0 g/dL (obtained ≤ 14 days prior to registration)
• REGISTRATION: Absolute neutrophil count (ANC) ≥ 1500/mm\^3 (obtained ≤ 14 days prior to registration)
• REGISTRATION: Platelet count ≥ 100,000/mm\^3 (obtained ≤ 14 days prior to registration)
• REGISTRATION: Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 14 days prior to registration)
• REGISTRATION: Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3 x ULN (≤ 5 x ULN for patients with liver involvement) (obtained ≤ 14 days prior to registration)
• REGISTRATION: Prothrombin time (PT)/international normalized ratio (INR)/activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN (obtained ≤ 14 days prior to registration) OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy

You may not qualify if:

• REGISTRATION: Any of the following:
• Pregnant women
• Nursing women
• Men or women who are of childbearing potential who are unwilling to employ adequate contraception
• REGISTRATION: Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• REGISTRATION: Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy
• NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
• REGISTRATION: Failure to recover from acute, reversible effects of prior therapy regardless of interval since last treatment
• EXCEPTION: Grade 1 peripheral (sensory) neuropathy that has been stable for at least 3 months since completion of prior treatment
• REGISTRATION: Uncontrolled intercurrent illness including, but not limited to:
• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Or psychiatric illness/social situations that would limit compliance with study requirements

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

RECRUITING

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Interventions

Specimen Handling; Drug Therapy; Decitabine; Injections; Congresses as Topic; Radiation; Surgical Procedures, Operative

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Therapeutics; Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Drug Administration Routes; Organizations; Health Care Economics and Organizations; Physical Phenomena

Study Officials

• Adam L. Holtzman, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trials Referral Office

CONTACT

855-776-0015; mayocliniccancerstudies@mayo.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2025
• First Posted: May 30, 2025
• Study Start: January 23, 2026
• Primary Completion (Estimated): November 8, 2027
• Study Completion (Estimated): November 8, 2027
• Last Updated: January 26, 2026

Record last verified: 2026-01

Locations

US (1)