Clinical Trials

Inclusion Criteria

• Age ≥18 years
• Histologic confirmation of HPV-negative squamous cell carcinoma of the head and neck including of the oral cavity, oropharynx, larynx (supraglottic, glottic, subglottic), hypopharynx
• Absence of distant metastases on standard diagnostic work-up ≤ 16 weeks prior to registration. (Chest CT or PET/CT).
• Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only.
• ECOG Performance Status (PS) ≤ 1 (Appendix I)
• Provide written informed consent
• The following laboratory values obtained ≤14 days prior to registration: (Verify this matches Section 4.0) (RPS verify window and replace with “randomization” if a randomized study.)
• • Hemoglobin ≥9.0 g/dL
  • Absolute neutrophil count (ANC) ≥1500/mm3
  • Platelet count ≥100,000/mm3
  • Total bilirubin ≤1.5 x ULN
  • Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤3 x ULN (≤5 x ULN for patients with liver involvement)
  • PT/INR/aPTT ≤1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy
• Willingness to provide mandatory tissue specimens for correlative research (see Section 17.0)

Exclusion Criteria

• Any of the following:
  • Pregnant women
  • Nursing women
  • Men or women who are of childbearing potential who are unwilling to employ adequate contraception.
•  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.
• Immunocompromised patients and patients known to be HIV+.
• 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.
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
• Other active malignancy ≤ 5 years prior to registration.

EXCEPTIONS: Nonmelanotic skin cancer or carcinoma-in-situ of the cervix, or prostate or localized endometrioid endometrial cancer.

NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer.

• Prior history of radiation therapy to the affected site.
• Prior systemic chemotherapy in the last 5 years.
• Contraindication to radiation therapy as determined by the treating team.
• Contraindication to decitabine as determined by the treating team.

Pre-Registration – Exclusion Criteria

Any of the following:

• Pregnant women
• Nursing women
• Men or women who are of childbearing potential who are unwilling to employ adequate contraception.
• 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.
• Immunocompromised patients and patients known to be HIV+.
• 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.
•  Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
• Other active malignancy ≤ 5 years prior to registration.

EXCEPTIONS: Nonmelanotic skin cancer or carcinoma-in-situ of the cervix, or prostate or localized endometrioid endometrial cancer.

NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer.

• Prior history of radiation therapy to the affected site.
• Prior systemic chemotherapy in the last 5 years.
• Contraindication to radiation therapy as determined by the treating team.
• Contraindication to decitabine as determined by the treating team.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 3/27/2025. Questions regarding updates should be directed to the study team contact.