Bevacizumab, Cetuximab, and Cisplatin With IMRT (Intensity-Modulated Radiation Therapy) for Patients With Stage III/IV Head and Neck Squamous Cell Carcinoma

Inclusion Criteria:

* Stage III/IV HNSCC without distant metastasis. Patients with stage II squamous cell carcinoma of the hypopharynx will also be eligible
* Adequate renal function, with serum creatinine ≤ 1.5 mg/dL. Patients with serum creatinine \> 1.5 mg/dL may be eligible if calculated creatinine clearance \> or = to 55 ml/min by Cockcroft and Gault equation (or 24-hour urine collection).
* Age \> or = to 18 years.
* Karnofsky performance status \> or = to 70%
* Adequate bone marrow function: absolute neutrophil count \> or = to 1,500/ platelets \> or = to 100,000/ul, hemoglobin \> or = to 9 gm/dl
* Adequate hepatic function: Total bilirubin ≤ 1.5 X ULN (patients with Gilbert's syndrome as the cause of hyperbilirubinemia may be eligible if total bilirubin ≤ 2.5 X ULN), aspartate aminotransferase (AST) ≤ 2.5 X ULN, alanine aminotransferase (ALT) ≤ 2.5 X ULN, alkaline phosphatase ≤ 2.5 X ULN.
* Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.
* Patients must have ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

* Prior radiation therapy for HNSCC
* Prior treatment of HNSCC with bevacizumab or other agents specifically targeting VEGF
* Prior treatment of HNSCC with cetuximab or other agents specifically targeting EGFR
* Other active malignancy, other than indolent malignancies, which the investigator determines are unlikely to interfere with treatment or efficacy analysis. For example, patients with non-melanoma skin cancer, in situ carcinoma of the cervix, or prostate cancer within the no current biochemical (PSA) or radiologic evidence of disease may enroll.
* Patients with nasopharyngeal carcinoma
* Patients who will receive amifostine as part of the radiation treatment plan
* Patients with skin breakdown/ulceration (CTCAE version 3.0, grade 2 or higher).
* Patients with hearing loss requiring hearing aid or intervention (i.e. interfering in a clinically significant way with activities of daily living).
* Patients with multifocal peripheral sensory alterations or paresthesias (including tingling) interfering with function, per patient report (example: activities of daily living).
* Any prior documented history of transient ischemic attack (TIA) or cerebrovascular accident (CVA)
* History of unstable angina or myocardial infarction (MI) within the last year.
* Urine protein: creatinine (UPC) ratio \> or = to 1.0 at screening. A random urine sample is collected. Total protein (mg/dL) and spot creatinine (mg/dL) are ordered for this sample. The UPC ratio is calculated from the results of these tests.
* International normalized ratio (INR) \> 1.5 or activated partial thromboplastin time (aPTT) \> 1.5 X upper limits of normal (ULN)
* Current use of warfarin, current use of heparin or low-molecular weight heparin, chronic daily treatment with aspirin (\> 325 mg/day) or nonsteroidal anti-inflammatory medications known to inhibit platelet function.
* Patients with gross hemoptysis or hematemesis (defined as bright red blood of 1 teaspoon of more) within 28 days prior to Day 0 protocol treatment will be excluded from this trial. Patients with incidental blood mixed with phlegm are not excluded.
* Esophageal varices, non-healing ulcer, wound, or bone fracture are exclusion criteria. However, patients with skin breakdown overlying malignant neck lymphadenopathy may be eligible, at the discretion of the investigator.
* Anatomic lesion that increases the risk of serious hemorrhage, such as encasement or invasion of major blood vessels by primary tumor and/or by involved lymph nodes
* Blood pressure of \> 150/100 mmHg
* New York Heart Association (NYHA) Grade II or greater congestive heart failure.
* Clinically significant peripheral vascular disease
* History of bleeding diathesis or hemorrhagic disorder, or coagulopathy.
* Major surgical procedure or significant traumatic injury within 28 days prior to treatment with bevacizumab
* Core biopsy within 7 days prior to treatment with bevacizumab.
* Minor surgical procedures such as fine needle aspirations or placement of percutaneous gastrostomy tube (PEG) less than 7 days prior to treatment with bevacizumab
* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior enrollment.
* Inability to comply with study and/or follow-up procedures
* Women who are pregnant or lactating