Bevacizumab/Ph 2 for Locally Advanced Head and Neck Cancer

Inclusion Criteria:

* Patients with AJCC 7th edition stage III-IVB head and neck cancer, all sites, including unknown primary tumors.
* Prior to entry in the study the resectability and alternative treatment options for each patient will be determined by a team composed of an Ear, Nose, and Throat Surgeon, a Radiation Oncologist and a Medical Oncologist. Stage determination, optimal local treatment, and its timing according to this protocol will be determined at this evaluation. The unequivocal demonstration of distant metastasis (M1) confers ineligibility.
* Histologically or cytologically confirmed diagnosis of squamous cell or poorly differentiated carcinomas, or WHO types I-III of the nasopharynx.
* Unidimensionally measurable disease is required (RECIST 1.1).
* No prior chemotherapy, biologic/molecular targeted therapy (including any prior therapy which specifically and directly targets the EGFR pathway), or radiotherapy for head and neck cancer.
* Prior surgical therapy will consist only of incisional or excisional biopsy, and organ sparing procedures such as debulking of airway compromising tumors or neck dissection in a patient with an existing primary tumor. Any non-biopsy procedure must have taken place \> 4 weeks but \< 3 months of initiating protocol treatment.
* ECOG performance status 0-1.
* Age 18 years or older.
* Informed consent must be obtained from all patients prior to beginning therapy. Patients should have the ability to understand and the willingness to sign a written informed consent document.
* All patients should have their tumor tissue tested for HPV (in situ hybridization and/or p16 staining by immunohistochemistry), and results must be known prior to study entry, and will consent to have available archival tumor samples, unstained slides or blocks from previous diagnostic or therapeutic procedures submitted for correlative studies, including assessment of target molecules EGFR, VEGF and related biomarkers. Also, patients must agree to submit blood samples for correlative studies at least at baseline.
* Absolute neutrophil count at or above 1500/µl, Platelet count at or above 100,000/µl
* Creatinine clearance 60 ml/min or higher calculated using the Cockcroft-Gault formula:

Calculated Creatinine Clearance = (140-age) X actual body wt (kg)/ 72 X serum creatinine Multiply this number by 0.85 if the patient is female

* Total bilirubin within normal limits and AST/ALT less than 3 times the upper limit of normal.
* Urine dipstick must be \< 0-1+ within 2 weeks (14 days) of randomization. If urine dipstick result is \> 1+, a calculation of Urine Protein Creatinine (UPC) ratio is required. Patients must have a UPC ratio \< 1.0 to participate in the study.

NOTE: UPC ratio of spot urine is an estimation of the 24-urine protein excretion - a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1gm. UPC ratio is calculated using one of the following formula:

* \[urine protein\]/\[urine creatinine\] - if both protein and creatinine are reported in mg/DI
* \[(urine protein) × 0.088\]/\[urine creatinine\] - if urine creatinine is reported in mmol/L

  * Patients with a prior history of squamous cell or basal carcinoma of the skin or in situ cervical cancer must have been curatively treated. Patients with a history of other prior malignancy must have been treated with curative intent and must have remained disease-free for 3 years post diagnosis.
  * Patients may not be receiving any other investigational agents.

Exclusion Criteria:

* History of severe allergic reactions attributed to docetaxel or compounds of similar chemical or biologic composition to docetaxel, or other drugs formulated with polysorbate 80.
* Prior severe infusion reaction to a monoclonal antibody or known hypersensitivity to any component of bevacizumab
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
* All patients will have a baseline EKG. If abnormalities consistent with active coronary artery disease are detected, the patient will be referred to a cardiologist for appropriate evaluation and management prior to treatment on study
* No patients with significant baseline sensory or motor neurologic deficits (\> grade I neuropathy) will be treated on this study.
* Because patients with immune deficiency are at increased risk of lethal Infections when treated with marrow-suppressive therapy, HIV-positive patients are excluded from the study. Appropriate studies will be undertaken in patients with HIV and those receiving combination anti- retroviral therapies when indicated.
* Patients with HPV positive tumors (P16+ by immunohistochemistry and/or HPV+ by in situ hybridization) AND smoking history =\<10 pack-years
* Inadequately controlled hypertension (defined as systolic blood pressure \>150 mmHg and/or diastolic blood pressure \>100 mmHg)
* Prior history of hypertensive crisis or hypertensive encephalopathy
* New York Heart Association (NYHA) Grade II or greater congestive heart failure
* History of myocardial infarction or unstable angina within 12 months prior to Day 1
* No history of stroke or transient ischemic attack within 6 months prior to Day 1
* Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
* History of hemoptysis (\> or = to 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1
* Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
* Patients should not be on therapeutic anticoagulation therapy (prophylactic use of warfarin 1mg per day is allowed) and INR should be \<1.5 at registration
* The use of anti-platelet agents (e.g. dipyridamole (Persatine), ticlopidine (Ticlid), clopidogrel (Plavix)) is allowed only if patient is not receiving aspirin or NSAID's known to inhibit platelet function.
* Major surgical procedure (including neck dissection), open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study
* Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
* History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1
* Serious, non-healing wound, active ulcer, or untreated bone fracture
* Pregnant or breast-feeding women will be excluded.