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

February 6, 2013 updated by: National Cancer Institute (NCI)

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

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. 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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. 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.

II. Determine the time to progression, pattern of failure, local control, and distant failure rate in patients treated with this regimen.

III. 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.

Study Type

Interventional

Enrollment (Actual)

39

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60637-1470
        • University of Chicago Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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
  • Performance status - ECOG 0-2
  • Performance status - Karnofsky 60-100%
  • More than 12 weeks
  • 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
  • Bilirubin normal
  • AST/ALT no greater than 2.5 times upper limit of normal
  • Creatinine normal
  • Urine protein no greater than trace
  • Urine protein less than 0.5 g/24 hours
  • No significant renal impairment
  • 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
  • No hemoptysis of at least 1 tablespoon
  • 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
  • No prior fluorouracil and hydroxyurea with radiotherapy
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
  • See Disease Characteristics
  • See Chemotherapy
  • At least 4 months since prior radiotherapy and recovered
  • At least 4 weeks since prior major surgery
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (hydroxyurea, fluorouracil, bevacizumab, radiation)
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 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.
Other: laboratory biomarker analysis
Correlative studies
Biological: bevacizumab
Given IV
Other Names:
  • Avastin
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • rhuMAb VEGF
Drug: fluorouracil
Given IV
Other Names:
  • 5-FU
  • 5-fluorouracil
  • 5-Fluracil
Radiation: radiation therapy
Undergo radiotherapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Biological: filgrastim
Given subcutaneously
Other Names:
  • G-CSF
  • Neupogen
Drug: hydroxyurea
Given orally
Other Names:
  • HU
  • HYD
  • Hydrea
  • Hydroxycarbamide
  • Hydurea

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
MTD defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity assessed using NCI CTCAE version 3.0
Time Frame: 14 weeks
14 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate (CR+PR) assessed using RECIST criteria
Time Frame: Up to 9 years
The associated 95% confidence interval will be determined.
Up to 9 years
Pattern of failure, described as locoregional, distant, or both
Time Frame: Up to 9 years
Up to 9 years
Duration of response
Time Frame: From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 9 years
From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 9 years
Progression free survival
Time Frame: From the date of registration to the date of progressive disease or death, assessed up to 9 years
Will be calculated using the Kaplan-Meier method, and median progression-free and overall survival times, along with their 95% confidence intervals, will be derived using the procedure described in Brookmeyer and Crowley.
From the date of registration to the date of progressive disease or death, assessed up to 9 years
Overall survival
Time Frame: From the date of registration to the date of death, assessed up to 9 years
Will be calculated using the Kaplan-Meier method, and median progression-free and overall survival times, along with their 95% confidence intervals, will be derived using the procedure described in Brookmeyer and Crowley.
From the date of registration to the date of death, assessed up to 9 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Everett Vokes, University of Chicago Comprehensive Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2001

Primary Completion (Actual)

March 1, 2010

Study Registration Dates

First Submitted

September 13, 2001

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

February 7, 2013

Last Update Submitted That Met QC Criteria

February 6, 2013

Last Verified

February 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02408
  • 11033B
  • CDR0000068879 (Registry Identifier: PDQ (Physician Data Query))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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