A Phase I/II Study Of Bevacizumab (rhuMAb VEGF) In Combination With OSI-774 For Patients With Recurrent Or Metastatic Cancer Of The Head And Neck

Inclusion Criteria:

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

- Recurrent or metastatic disease

- Determined to be incurable by surgery or radiotherapy

- Measurable disease

- No tumor involvement encasing or too close in proximity to a major artery or vein

- No known brain metastases

- No prior or concurrent CNS disease

- No primary brain tumor

- Performance status - ECOG 0-2

- Performance status - Karnofsky 60-100%

- More than 12 weeks

- No history of bleeding diathesis

- WBC at least 3,000/mm^3

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- INR less than 1.5

- Bilirubin normal

- AST and ALT no greater than 2.5 times upper limit of normal

- Creatinine normal

- Creatinine clearance at least 60 mL/min

- No significant renal impairment

- 24-hour urinary protein less than 0.5 g required if more than trace proteinuria at
baseline

- No uncontrolled hypertension

- No symptomatic congestive heart failure

- No serious cardiac arrhythmia requiring medication

- No deep venous thrombosis

- No prior stroke

- No New York Heart Association class II-IV heart disease

- No grade II-IV peripheral vascular disease within the past year

- No arterial thromboembolic event within the past 6 months, including any of the
following:

- Unstable angina pectoris

- Myocardial infarction

- Transient ischemic attack

- Cerebrovascular accident

- No clinically significant peripheral artery disease

- No significant ophthalmologic abnormalities* including any of the following:

- Severe dry eye syndrome

- Keratoconjunctivitis sicca

- Sjögren's syndrome

- Severe exposure keratopathy

- Disorders that might increase the risk for epithelium-related complications
(e.g., bullous keratopathy, aniridia, severe chemical burns, neutrophilic
keratitis)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No prior allergic reactions to compounds of similar chemical or biologic composition
to bevacizumab or other study agents

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

- No significant traumatic injury within the past 28 days

- No other concurrent uncontrolled illness

- No psychiatric illness or social situation that would preclude study compliance

- No ongoing or active infection requiring parenteral antibiotics

- No serious non-healing wound ulcer or bone fracture

- No seizures not controlled by standard medical therapy

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

- More than 4 weeks since prior radiotherapy

- More than 4 weeks since prior major surgery

- More than 4 weeks since prior open biopsy

- Recovered from prior therapy

- No more than 1 prior regimen for recurrent disease

- No prior epidermal growth factor receptor (EGFR)-based therapy for recurrent disease

- No prior vascular EGFR-based therapy for recurrent disease

- No other concurrent investigational agents

- No other concurrent anticancer agents or therapies

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent chronic use of aspirin (325 mg/day or more) or other nonsteroidal
anti-inflammatory drugs

- No concurrent warfarin or heparin, including low-molecular weight heparin

- No other concurrent or recent (within 1 month) thrombolytic agents or full-dose
anticoagulants (except to maintain patency of preexisting, permanent indwelling IV
catheters)