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Human Papillomavirus-Negative Neck Squamous Cell CarcinomaPhase 1NCT06997094

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

A Phase 1 study testing Biospecimen Collection, Chemotherapy and Decitabine in people with Human Papillomavirus-Negative Neck Squamous Cell Carcinoma and Resectable Head and Neck Squamous Cell Carcinoma, run by Mayo Clinic at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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)… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Chemotherapy and Decitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
1 siteUnited States
Study dates
23 Jan 2026to 8 Nov 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Clinical Trials Referral Office contact

855-776-0015

mayocliniccancerstudies@mayo.edu

United States1 site, 1 recruiting

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

    Clinical Trials Referral Office, 855-776-0015, mayocliniccancerstudies@mayo.edu

    Adam L. Holtzman, MD

    Recruiting

Other trials in United States

About this study

Official title: Phase I Decitabine Dose-Tolerance in Surgically Resectable HPV-Negative Head and Neck Cancer

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To prospectively evaluate the maximum tolerated dose (MTD) of decitabine, in both the preoperative and adjuvant phases of treatment, combined with standard-of-care therapy including surgery +/- chemoradiation for HPV-negative head and neck cancers.

SECONDARY OBJECTIVES:

  1. Evaluation of acute (early onset) toxicities. (Stratified by methylation status) II. Evaluation of late onset toxicities. (Stratified by methylation status) III. Evaluation of event-free survival (EFS). (Stratified by methylation status) IV. Evaluation of overall survival (OS). (Stratified by methylation status) V. Evaluation of quality of life (QOL). (Stratified by methylation status)

CORRELATIVE RESEARCH OBJECTIVES:

  1. In vivo methylation response to preoperative decitabine. II. Pharmacokinetics of decitabine. III. Exploratory circulating biomarkers.

OUTLINE: This is a dose-escalation study followed by a dose-expansion study.

PREOPERATIVE PHASE: Patients receive decitabine intravenously (IV) over 1 hour once daily (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.

After completion of study treatment, patients are followed up at 30 days, every 4-6 months for 2 years and then every 12 months for up to 5 years.

Being tested
Biospecimen Collection, Chemotherapy, Decitabine, External Beam Radiation Therapy, Questionnaire Administration

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • ChemotherapyDrug

    Also called Chemo, Chemotherapy (NOS), Chemotherapy, Cancer, General

    Given concurrent chemotherapy

  • DecitabineDrug

    Also called 5-Aza-2'-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine

    Given IV

  • External Beam Radiation TherapyRadiation

    Also called Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam Radiotherapy

    Undergo EBRT

  • Questionnaire AdministrationOther

    Ancillary studies

  • Surgical ProcedureProcedure or surgery

    Also called Operation, Surgery, Surgery Type, Surgery, NOS

    Undergo standard of care surgery

Study groups in NCT06997094
Study groupRoleWhat they receive
Treatment (decitabine, surgery, radiation)ExperimentalPREOPERATIVE 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.
Receives: Procedure: Biospecimen Collection; Drug: Chemotherapy; Drug: Decitabine; Radiation: External Beam Radiation Therapy; Other: Questionnaire Administration; Procedure: Surgical Procedure

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose (MTD) of preoperative decitabine

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

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

  2. MTD of adjuvant decitabine

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

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

Secondary outcomes (5)

  1. Incidence of acute (early onset) adverse events

    Defined as toxicities which begin during the start of adjuvant therapy until 90 days post end of treatment. Will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The maximum grade for each type of acute AE will be recorded for each patient.

    Measured: Up to 90 days

  2. Incidence of late onset adverse events

    Defined as toxicities which begin from 91 days to two years post radiation therapy. Early onset toxicities can also be considered late toxicities if they persist for at least one day beyond the 90 days used to define late onset toxicities. Will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The maximum grade for each type of acute AE will be recorded for each patient.

    Measured: From 91 days to 2 years

  3. Event-free survival

    Defined as the interval from registration to last follow-up without an event, defined to include 1) recurrence of disease, 2) progression of disease, or 3) death.

    Measured: 1 year, 2 years, 5 years

  4. Overall survival

    Defined as the interval from registration to last follow-up or death from any cause.

    Measured: 1 year, 2 years, 5 years

  5. Quality of Life - EORTC QLQ-H&N35

    Assessed using the EORTC (European Organization for Research and Treatment of Cancer) QLQ (Quality of Life) - Head \& Neck 35 (H\&N35) inventory, a 35-item questionnaire that assesses symptoms encountered specifically by patients with head and neck cancer. This measure generates 7 multiple-item scales (Pain, Swallowing, Senses, Speech, Social eating, Social contact, and Sexuality), in addition to 11 single items (e.g., opening mouth, sticky saliva, dry mouth). Scales range in score from 0 to 100. A high score for a functional scale represents a high/healthy level of functioning whereas a high score for a symptom scale or item represents a high level of symptomatology or problems.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 May 2025
  2. Study start23 Jan 2026
  3. Primary completion8 Nov 2027 (estimated)
  4. Study completion8 Nov 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
32 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06997094
Sponsor's protocol ID
MC240706
Other IDs
24-012507
Status last verified
Jul 2026
First submitted
21 May 2025
Last updated
15 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Biospecimen Collection, Chemotherapy and Decitabine in people with Human Papillomavirus-Negative Neck Squamous Cell Carcinoma and Resectable Head and Neck Squamous Cell Carcinoma, run by Mayo Clinic at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 15 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Clinical Trials Referral Office (855-776-0015, mayocliniccancerstudies@mayo.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06997094.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2026.

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