RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes needed for tumor cell growth. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. Combining erlotinib with bevacizumab may kill more tumor cells.

PURPOSE: This randomized phase I/II trial is to see if combining erlotinib with bevacizumab works better in treating patients who have recurrent or metastatic head and neck cancer.

Condition	Treatment or Intervention	Phase
Head and Neck Cancer	Drug: bevacizumab  Drug: erlotinib  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: enzyme inhibitor therapy  Procedure: growth factor antagonist therapy  Procedure: monoclonal antibody therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase I Phase II

Further Study Details: 

OBJECTIVES:

• 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.
• 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.

• 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.
• Course 1 is 28 days in length. All subsequent courses are 21 days.
• Patients are randomized to 1 of 2 treatment arms.
• Arm I: Patients receive bevacizumab IV over 30-90 minutes on day 14 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.

PROJECTED ACCRUAL: A total of 9-18 patients will be accrued for the phase I portion of this study within 2-9 months and 40 patients for the phase II portion of this study within 8-20 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 12 weeks

Hematopoietic

• 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

Hepatic

• INR less than 1.5
• Bilirubin normal
• AST and ALT no greater than 2.5 times upper limit of normal

Renal

• Creatinine normal OR
• 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

Cardiovascular

• 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

Ophthalmologic

• 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) NOTE: *Patients with mild forms of the abnormalities, asymptomatic history, or normal ophthalmologic examination may be eligible at the discretion of the investigator

Other

• 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

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

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

Endocrine therapy

• Not specified

Radiotherapy

• More than 4 weeks since prior radiotherapy

Surgery

• More than 4 weeks since prior major surgery
• More than 4 weeks since prior open biopsy

Other

• 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)

Illinois
      Cardinal Bernardin Cancer Center at Loyola University Medical Center, Maywood,  Illinois,  60153,  United States; Recruiting
      Central Illinois Hematology Oncology Center, Springfield,  Illinois,  62701,  United States; Recruiting
      Decatur Memorial Hospital Cancer Care Institute, Decatur,  Illinois,  62526,  United States; Recruiting
      Evanston Northwestern Health Care - Evanston Hospital, Evanston,  Illinois,  60201-1781,  United States; Recruiting
      Ingalls Cancer Care Center at Ingalls Memorial Hospital, Harvey,  Illinois,  60426,  United States; Recruiting
      La Grange Memorial Hospital, La Grange,  Illinois,  60525,  United States; Recruiting
      Louis A. Weiss Memorial Hospital, Chicago,  Illinois,  60640,  United States; Recruiting
      Oncology/Hematology Associates of Central Illinois, P.C., Peoria,  Illinois,  61615-7828,  United States; Recruiting
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States; Recruiting
      University of Illinois Medical Center, Chicago,  Illinois,  60612-7317,  United States; Recruiting
Indiana
      CCOP - Northern Indiana CR Consortium, South Bend,  Indiana,  46601,  United States; Recruiting
      Fort Wayne Medical Oncology and Hematology, Incorporated, Fort Wayne,  Indiana,  46885-5099,  United States; Recruiting
Michigan
      Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph, Saint Joseph,  Michigan,  49085,  United States; Recruiting
Wisconsin
      Medical College of Wisconsin Cancer Center, Milwaukee,  Wisconsin,  53226,  United States; Recruiting

Study chairs or principal investigators

Ezra Cohen, MD,  Principal Investigator,  University of Chicago Cancer Research Center   

Study ID Numbers:  CDR0000271444; UCCRC-11956A; NCI-5701; UCCRC-NCI-5701; NCT00055913
Record last reviewed:  September 2004
Last Updated:  April 4, 2005
Record first received:  March 6, 2003
ClinicalTrials.gov Identifier:  NCT00055913
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08