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

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Closed 18 and over NCI UCCRC-11956A NCI-5701, UCCRC-NCI-5701, NCT00055913, 5701

Objectives

1. 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.
2. Determine the objective response rate and stable disease/absence of early progression in patients treated with this regimen.

Entry 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

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)

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

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

Expected Enrollment

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.

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.
  
  
  

Trial Contact Information

Trial Lead Organizations

University of Chicago Cancer Research Center

Ezra Cohen, MD, Principal investigator		Ph: 773-702-4137; 888-824-0200 Email: ecohen@medicine.bsd.uchicago.edu

Registry Information
Official Title		A Phase I/II Study Of Bevacizumab (rhuMAb VEGF) In Combination With OSI-774 For Patients With Recurrent Or Metastatic Cancer Of The Head And Neck
Trial Start Date		2003-05-08
Trial Completion Date		2004-05-26 (estimated)
Registered in ClinicalTrials.gov		NCT00055913
Date Submitted to PDQ		2003-01-23
Information Last Verified		2005-06-02
NCI Grant/Contract Number		CA14599, CM17102

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