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 1+, a calculation of Urine Protein Creatinine (UPC) ratio is required. Patients must have a UPC ratio 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 = 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.