Bevacizumab and Erlotinib in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose and dose-limiting toxicity of bevacizumab when administered with erlotinib in patients with recurrent or metastatic head and neck cancer.

II. Determine the objective response rate and stable disease/absence of early progression in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of bevacizumab followed by a randomized, multicenter study.

Phase I: Patients receive bevacizumab IV over 30-90 minutes on day 1 and oral erlotinib on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of bevacizumab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Phase II: Course 1 is 28 days in length. All subsequent courses are 21 days.

Course 1: Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive bevacizumab IV over 30-90 minutes on day 15 and oral erlotinib on days 1-28.

Arm II: Patients receive bevacizumab IV over 30-90 minutes on day 1 and oral erlotinib on days 1-28.

All subsequent courses: All patients receive bevacizumab as in arm II and oral erlotinib on days 1-21.

Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

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)