RATIONALE: 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. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining monoclonal antibody therapy with chemotherapy and radiation therapy may be an effective treatment for head and neck cancer.

PURPOSE: This phase I trial is to see if combining bevacizumab, fluorouracil, and hydroxyurea with radiation therapy works in treating patients who have advanced head and neck cancer.

Condition	Treatment or Intervention	Phase
Head and Neck Cancer	Drug: bevacizumab  Drug: filgrastim  Drug: fluorouracil  Drug: hydroxyurea  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: growth factor antagonist therapy  Procedure: monoclonal antibody therapy  Procedure: radiation therapy	Phase I

Further Study Details: 

OBJECTIVES:

• Determine the maximum tolerated dose and dose-limiting toxicity of bevacizumab when given in combination with fluorouracil, hydroxyurea, and radiotherapy in patients with advanced head and neck cancer.
• Determine the time to progression, pattern of failure, local control, and distant failure rate in patients treated with this regimen.
• Determine the local toxic effects of this regimen in these patients.

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

Patients receive oral hydroxyurea every 12 hours on days 1-6, fluorouracil IV continuously on days 1-5, and bevacizumab IV over 90 minutes on day 1. Patients also undergo radiotherapy once daily on days 1-5. Patients receive filgrastim (G-CSF) subcutaneously on days 6-12. Treatment repeats every 2 weeks for up to 7 courses 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 at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Additional patients are treated at the MTD.

PROJECTED ACCRUAL: A total of 27-39 patients will be accrued for this study within 5.4-19.5 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed advanced head and neck cancer
• Requiring regional palliative radiotherapy
• Not amenable to standard therapy
• Previously untreated disease allowed only if prognosis is poor (i.e., estimated 2-year survival of less than 10% if treated with standard therapy alone)
• No obvious tumor involvement of major vessels on CT scan
• No known brain metastases

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy:

• More than 12 weeks

Hematopoietic:

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• No history of bleeding diathesis

Hepatic:

• Bilirubin normal
• AST/ALT no greater than 2.5 times upper limit of normal

Renal:

• Creatinine normal
• Urine protein no greater than trace OR
• Urine protein less than 0.5 g/24 hours
• No significant renal impairment

Cardiovascular:

• No symptomatic congestive heart failure
• No cardiac arrhythmia
• No deep venous thrombosis
• No uncontrolled hypertension
• No clinically significant peripheral artery disease
• No arterial thromboembolic event within the past 6 months, including any of the following:
• Transient ischemic attack
• Cerebrovascular accident
• Unstable angina
• Myocardial infarction

Pulmonary:

• No hemoptysis of at least 1 tablespoon

Other:

• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab or other agents used in this study
• No non-healing wounds within the past 4 weeks
• No significant ongoing or active infection
• No other uncontrolled illness
• No other severe complicating medical illness that would preclude study participation
• No psychiatric illness or social situation that would preclude study compliance
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• No prior fluorouracil and hydroxyurea with radiotherapy
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• See Chemotherapy
• At least 4 months since prior radiotherapy and recovered

Surgery:

• At least 4 weeks since prior major surgery

Other:

• No prior or concurrent chronic use of aspirin or other nonsteroidal anti-inflammatory agents
• No other concurrent investigational agents
• No concurrent anticoagulation therapy
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent anticancer agents

Illinois
      Central Illinois Hematology Oncology Center, Springfield,  Illinois,  62701,  United States
      Evanston Northwestern Health Care - Evanston Hospital, Evanston,  Illinois,  60201-1781,  United States
      Robert H. Lurie Comprehensive Cancer Center at Northwestern University, Chicago,  Illinois,  60611-3013,  United States
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States

Study chairs or principal investigators

David M. Gustin, MD,  Study Chair,  University of Chicago Cancer Research Center   

Study ID Numbers:  CDR0000068879; UCCRC-11033; NCI-2630
Record last reviewed:  December 2004
Last Updated:  December 9, 2004
Record first received:  September 13, 2001
ClinicalTrials.gov Identifier:  NCT00023959
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08