Comparing Radiation Plus Cetuximab to Radiation Plus Chemotherapy in People With Advanced Head and Neck Cancer Who Cannot Receive Cisplatin

You may be eligible if

• Patients must have pathologically confirmed, previously untreated, unresected squamous cell carcinoma of the larynx, hypopharynx, oropharynx, or oral cavity
• Local evaluation of p16 status is required for all oropharynx patients prior to registration
• Local evaluation of p16 status is recommended for non-oropharynx patients prior to registration
• Locoregionally advanced head and neck squamous cell carcinoma (HNSCC) defined as:
• * Non-oropharynx and p16-negative oropharynx cancer: American Joint Commission on Cancer (AJCC) 9th edition stage III-IVB
• * Eligible Laryngeal, Hypopharyngeal, Oral Cavity, and p16-Negative Oropharyngeal Primaries:
• * AJCC 9th Edition TNM: T3 N0 or T1-3 N1 M0; AJCC 9th Edition Stage: III
• * AJCC 9th Edition TNM: T1-3 N2 or T4a N0-N2 M0; AJCC 9th Edition Stage: IVA
• * AJCC 9th Edition TNM: T4b N0-N2 or T1-4b N3 M0; AJCC 9th Edition Stage: IVB
• * p16-positive oropharynx cancer: AJCC 9th edition stage II-III
• * Eligible p16-Positive Oropharyngeal Primaries
• * AJCC 9th Edition TNM: T3 N0-2 or T1-2 N2 M0; AJCC 9th Edition Stage: II
• * AJCC 9th Edition TNM: T4 N0-3 or T1-3 N3 M0; AJCC 9th Edition Stage: III
• The following are required prior to registration:
• * Imaging of the head and neck with a neck CT or MRI (with contrast, unless contraindicated) or PET/CT which includes diagnostic-quality CT of the neck (with contrast, unless contraindicated)
• * Chest imaging: Chest CT (with contrast, unless contraindicated) or PET/CT
• Age ≥ 18
• Complete the online tool at www.nrgoncology.org prior to registration and record the (modified) Charleston Comorbidity Index (CCI), Head and Neck Cancer Intergroup (HNCIG) omega, and G-8 scores on the registration form in Oncology Patient Enrollment Network (OPEN)
• Patients must have a contraindication to cisplatin as defined in the following bullet points:
• * Absolute or relative contraindication to cisplatin, defined as ONE OR MORE of the following prior to registration:
• * Creatinine clearance (CrCl) \< 60 mL/min by the Cockroft-Gault formula
• * Pre-existing peripheral (sensory or motor) neuropathy grade ≥ 2 (per Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 5.0)
• * History of hearing loss, defined as either:
• * Existing need of a hearing aid OR
• * ≥ 25 decibel shift over 2 contiguous frequencies on a pretreatment hearing test as clinically indicated OR
• * age ≥ 70 with Head and Neck Cancer Intergroup (HNCIG) omega score \< 0.80 prior to registration OR
• * Age \< 70 with ALL of the following conditions prior to registration (see Appendix II for calculation instructions):
• * HNCIG omega score \< 0.80
• * (Modified) Charlson Comorbidity Index (CCI) ≥ 1
• * G-8 score ≤ 14
• Not pregnant and not nursing
• Participants must be able to safely receive the radiation and drug regimens per current Food and Drug Administration (FDA)-approved package insert(s), treating investigator's discretion, and institutional guidelines
• No prior systemic therapy for the study cancer; note that prior systemic therapy for a different cancer is allowable
• No prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• No prior surgery for the study cancer