Inclusion Criteria:

- Histologically or cytologically confirmed squamous cell carcinoma of the head and
neck

- Metastatic and/or recurrent disease

- Measurable disease defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by
conventional techniques or ≥ 10 mm by CT scan

- Not eligible for curative-intent surgery or radiotherapy

- No tumors invading major vessels (e.g., carotid artery) by imaging studies

- No history of major, uncontrolled tumor-related bleeding despite locoregional
treatment

- Not at high-risk for recurrent tumor-related bleeding

- No known brain metastases

- ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%

- Absolute neutrophil count ≥ 1,000/mm³

- Platelet count ≥ 75,000/mm³

- Bilirubin normal

- AST and ALT ≤ 5 times upper limit of normal (ULN)

- Creatinine normal OR creatinine clearance ≥ 60 mL/min

- Urine protein: creatinine ratio ≤ 0.5 OR urine protein < 1,000 mg by 24-hour urine
collection

- INR < 1.5

- No history of gross hemoptysis (defined as bright red blood of ≥ ½ teaspoon) or
coagulopathy

- No history of thrombosis (e.g., pulmonary embolism or deep venous thrombosis)

- No history of severe infusion reaction to a monoclonal antibody

- No CNS cerebrovascular ischemia or stroke within the past 6 months

- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
the past 4 weeks

- No significant traumatic injury within the past 4 weeks

- No unstable angina or myocardial infarction within the past 6 months

- No other malignancy within the past 3 years except curatively treated squamous cell
or basal cell skin cancer or in situ cervical cancer

- No uncontrolled illness including, but not limited to, any of the following:

- Serious nonhealing wound, ulcer, or bone fracture

- Symptomatic congestive heart failure

- Serious cardiac arrhythmia requiring medication

- Clinically significant peripheral vascular disease

- Active serious infection

- Other coexisting medical or psychiatric condition that would preclude study
compliance

- No uncontrolled hypertension (i.e., blood pressure > 150/100 mm Hg) despite a stable
regimen of antihypertensive therapy

- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 6 months after
completion of study treatment

- At least 3 weeks since prior biologic/targeted agents

- At least 3 weeks since prior radiotherapy

- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)

- At least 4 weeks since prior major surgical procedure or open biopsy

- At least 3 months since prior monoclonal antibody therapy

- No prior cetuximab, bevacizumab, or other epidermal growth factor receptor or
vascular endothelial growth factor-targeting agents

- No more than 1 prior adjuvant or neoadjuvant chemotherapy or chemoradiotherapy
regimen (may have included biologic therapy or a targeted agent)

- No more than 1 prior treatment regimen (e.g, chemotherapy or biologic/targeted
therapy) for recurrent or metastatic disease

- No concurrent major surgery

- No concurrent therapeutic anticoagulation except prophylactic warfarin 1 mg/day

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No other concurrent investigational agents

- No other concurrent anticancer agents or therapies