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

PRIMARY OBJECTIVES:

I. Determine the objective response rate in patients with recurrent or metastatic squamous
cell carcinoma of the head and neck treated with cetuximab and bevacizumab.

SECONDARY OBJECTIVES:

I. Determine the progression-free and overall survival of patients treated with this
regimen.

II. Determine the levels of soluble epidermal growth factor receptor (EGFR) in blood samples
before and after dual EGFR and vascular endothelial growth factor inhibition.

III. Evaluate treatment-related toxicities of this regimen in these patients. IV. Collect
and bank blood samples for future correlative studies.

OUTLINE: This is a multicenter study. Patients receive cetuximab intravenously (IV) over 1-2
hours on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats
every 21 days in the absence of disease progression or unacceptable toxicity.

Blood and tissue samples are collected at baseline to determine whether biomarkers on tumor
tissue and/or blood can be linked with clinical response and to measure signaling pathways
by reverse phase protein microarray. Epidermal growth factor receptor (EGFR) gene copy
number is assessed by fluorescent in situ hybridization (FISH) on tumor tissue pretreatment.
Blood samples are also collected at baseline and on day 21 of course 1 for analysis by
acridinium-linked immunosorbent assay (ALISA) to quantify serum p110 sEGFR protein levels.

After completion of study treatment, patients are followed every 2-3 months for 2 years and
then every 6 months for 3 years.

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