Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Bevacizumab, Fluorouracil, and Hydroxyurea Plus Radiation Therapy in Treating Patients With Advanced Head and Neck Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed 18 and over NCI UCCRC-11033 NCI-2630, NCT00023959, 2630

Objectives

1. 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.
2. Determine the time to progression, pattern of failure, local control, and distant failure rate in patients treated with this regimen.
3. Determine the local toxic effects of this regimen in these patients.

Entry 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

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

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/mm³
• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• 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

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

University of Chicago Cancer Research Center

Everett Vokes, MD, Protocol chair		Ph: 773-834-3093; 888-824-0200 Email: evokes@medicine.bsd.uchicago.edu

Registry Information
Official Title		A Phase I Study Of Bevacizumab (Recombinant Humanized Monoclonal Antibody To Vascular Endothelial Growth Factor) In Addition To Flourouracil And Hydroxyurea As Initial Chemotherapy With Concomitant Radiotherapy (B-FHX) For Poor Prognosis Head And Neck Cancer
Trial Start Date		2001-10-03
Registered in ClinicalTrials.gov		NCT00023959
Date Submitted to PDQ		2001-07-12
Information Last Verified		2004-11-17
NCI Grant/Contract Number		CM17102, CA14599, CA63187

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