Ipilimumab, Cetuximab, and Intensity-Modulated Radiation Therapy in Treating Patients With Previously Untreated Stage III-IVB Head and Neck Cancer

This is an interventional treatment trial for Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7 Read More

Inclusion Criteria:

• American Joint Committee on Cancer (AJCC) stage III/IVB, excluding T1N1, histologically or cytologically confirmed squamous cell carcinoma or undifferentiated carcinoma of the head and neck; patients should not have distant metastasis; primary sites include: oropharynx, hypopharynx, larynx

• Patients must have high or intermediate risk disease, defined as follows:

  • High risk: non-oropharyngeal subsite including larynx or hypopharynx (p16 status not required) or human papilloma virus (HPV)/p16- oropharynx subsite
  • Intermediate risk: HPV/p16+ oropharyngeal squamous cell cancer with: >= 10 pack (pk)-year (yr) smoking history and >= N2 nodal disease, or the presence of T4 tumor or N3 nodal disease, irrespective of smoking status
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
• Patients should be newly diagnosed HNSCC, with no prior therapy for this disease
• Eastern Cooperative Oncology Group (ECOG) performance status typically =< 1 (Karnofsky >= 70%)
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,200/mcL
• Platelets >= 75,000/mcL
• Total bilirubin =< 2 mg/dL (=< 3 mg/dL in case of Gilbert's syndrome)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2 times institutional upper limit of normal (IULN)
• Creatinine clearance >= 40 mL/min/1.73 m^2
• Patients must have the ability to understand and to sign written informed consent

Exclusion Criteria:

• Patients who have had prior chemotherapy, radiotherapy, or surgery with curative intent for HNSCC
• Patients with a history of prior treatment with ipilimumab, anti-programmed cell death 1 (PD 1) antibody, cluster of differentiation 137 (CD137) agonist or other immune activating therapy such as anti-cluster of differentiation 40 (CD 40) antibody
• Patients who are receiving any other investigational agents
• Autoimmune disease: patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, are excluded from this study, as are patients with a history of symptomatic non-gastrointestinal autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's granulomatosis]); central nervous system (CNS) or motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre syndrome and myasthenia gravis, multiple sclerosis)
• Patients with known immunodeficiency disorder, or presumed to be unable to respond to anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA 4) monoclonal antibody (mAb)
• Patients with distant metastatic disease (stage IVC)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to cetuximab or ipilimumab
• Patient is < 2 years free from a second primary malignancy unless the other malignancy is non-melanomatous skin cancer or an in-situ tumor treated with curative intent
• 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; patients with chronic hepatitis B or hepatitis C infections are excluded
• Pregnant women are excluded from this study
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible