Recruiting

Phase 1

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

Sponsor:

Mayo Clinic

Code:

NCT06997094

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

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Chemotherapy

Decitabine

External Beam Radiation Therapy

Questionnaire Administration

Study Details

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

Study ID

NCT06997094

Start date

Jan 23, 2026

Status verified date

Jul, 2026

Completion date

Nov 8, 2027

Anticipated

Primary completion date

Nov 8, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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
REGISTRATION: Provide written informed consent
REGISTRATION: Ability to complete questionnaire(s) by themselves or with assistance
REGISTRATION: Willingness to provide mandatory blood specimens for correlative research
REGISTRATION: Willingness to provide mandatory tissue specimens for correlative research
REGISTRATION: Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
RE-REGISTRATION FOR ADJUVANT DOSE ASSIGNMENT: Patient received pre-operative decitabine dose
RE-REGISTRATION FOR ADJUVANT DOSE ASSIGNMENT: The patient had study-specific surgery
RE-REGISTRATION FOR ADJUVANT DOSE ASSIGNMENT: Patient meets adjuvant radiation criteria based on investigator choice

Exclusion Criteria:

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
Dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy
REGISTRATION: Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
REGISTRATION: Other active malignancy ≤ 5 years prior to registration

EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix
NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer
REGISTRATION: History of myocardial infarction ≤ 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
REGISTRATION: Prior history of radiation therapy to the affected site
REGISTRATION: Prior systemic chemotherapy ≤ 5 years prior to registration for other diagnosis not related to study disease
REGISTRATION: Contraindication to radiation therapy as determined by the treating team
REGISTRATION: Contraindication to decitabine as determined by the treating team
RE-REGISTRATION FOR ADJUVANT DOSE ASSIGNMENT: Experienced a dose limiting toxicity (DLT) during pre-operative decitabine therapy

Study Design

Enrollment

32 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (decitabine, surgery, radiation)

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.

Interventions

Biospecimen Collection

Undergo blood sample collection

Chemotherapy

Given concurrent chemotherapy

Decitabine

Given IV

External Beam Radiation Therapy

Undergo EBRT

Questionnaire Administration

Ancillary studies

Surgical Procedure

Undergo standard of care surgery

Primary outcome measure

Maximum tolerated dose (MTD) of preoperative decitabine [ Time Frame: From first dose of preoperative decitabine to the first dose of adjuvant decitabine ]
MTD of adjuvant decitabine [ Time Frame: From first dose of adjuvant decitabine to 28 days after the end of treatment ]

Central Contacts and Locations

Central contacts

Clinical Trials Referral Office

855-776-0015 mayocliniccancerstudies@mayo.edu

Locations

Mayo Clinic in Florida

Recruiting

Jacksonville, Florida, United States, 32224-9980

Contacts

Clinical Trials Referral Office

855-776-0015 mayocliniccancerstudies@mayo.edu

Principal Investigator:

Adam L. Holtzman, MD

More Information

Sponsor

Mayo Clinic

Last update posted

Jul 15, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Mayo Clinic on 2026-07-15.