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

Primary Purpose

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma, Recurrent Adenoid Cystic Carcinoma of the Oral Cavity, Recurrent Basal Cell Carcinoma of the Lip

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
hydroxyurea
fluorouracil
bevacizumab
radiation therapy
filgrastim
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Chicago Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (hydroxyurea, fluorouracil, bevacizumab, radiation)

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Objective response rate (CR+PR) assessed using RECIST criteria
The associated 95% confidence interval will be determined.
Pattern of failure, described as locoregional, distant, or both
Duration of response
Progression free survival
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.
Overall survival
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.

Full Information

First Posted
September 13, 2001
Last Updated
February 6, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00023959
Brief Title
Bevacizumab, Fluorouracil, and Hydroxyurea Plus Radiation Therapy in Treating Patients With Advanced Head and Neck Cancer
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2013
Overall Recruitment Status
Completed
Study Start Date
July 2001 (undefined)
Primary Completion Date
March 2010 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma, Recurrent Adenoid Cystic Carcinoma of the Oral Cavity, Recurrent Basal Cell Carcinoma of the Lip, Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Recurrent Lymphoepithelioma of the Nasopharynx, Recurrent Lymphoepithelioma of the Oropharynx, Recurrent Metastatic Squamous Neck Cancer With Occult Primary, Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Recurrent Mucoepidermoid Carcinoma of the Oral Cavity, Recurrent Salivary Gland Cancer, Recurrent Squamous Cell Carcinoma of the Hypopharynx, Recurrent Squamous Cell Carcinoma of the Larynx, Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity, Recurrent Squamous Cell Carcinoma of the Nasopharynx, Recurrent Squamous Cell Carcinoma of the Oropharynx, Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Recurrent Verrucous Carcinoma of the Larynx, Recurrent Verrucous Carcinoma of the Oral Cavity, Stage III Adenoid Cystic Carcinoma of the Oral Cavity, Stage III Basal Cell Carcinoma of the Lip, Stage III Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Stage III Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Stage III Lymphoepithelioma of the Nasopharynx, Stage III Lymphoepithelioma of the Oropharynx, Stage III Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Stage III Mucoepidermoid Carcinoma of the Oral Cavity, Stage III Salivary Gland Cancer, Stage III Squamous Cell Carcinoma of the Hypopharynx, Stage III Squamous Cell Carcinoma of the Larynx, Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage III Squamous Cell Carcinoma of the Nasopharynx, Stage III Squamous Cell Carcinoma of the Oropharynx, Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage III Verrucous Carcinoma of the Larynx, Stage III Verrucous Carcinoma of the Oral Cavity, Stage IV Adenoid Cystic Carcinoma of the Oral Cavity, Stage IV Basal Cell Carcinoma of the Lip, Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Stage IV Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Stage IV Lymphoepithelioma of the Nasopharynx, Stage IV Lymphoepithelioma of the Oropharynx, Stage IV Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Stage IV Mucoepidermoid Carcinoma of the Oral Cavity, Stage IV Salivary Gland Cancer, Stage IV Squamous Cell Carcinoma of the Hypopharynx, Stage IV Squamous Cell Carcinoma of the Larynx, Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IV Squamous Cell Carcinoma of the Nasopharynx, Stage IV Squamous Cell Carcinoma of the Oropharynx, Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IV Verrucous Carcinoma of the Larynx, Stage IV Verrucous Carcinoma of the Oral Cavity, Untreated Metastatic Squamous Neck Cancer With Occult Primary

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
39 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (hydroxyurea, fluorouracil, bevacizumab, radiation)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
hydroxyurea
Other Intervention Name(s)
HU, HYD, Hydrea, Hydroxycarbamide, Hydurea
Intervention Description
Given orally
Intervention Type
Drug
Intervention Name(s)
fluorouracil
Other Intervention Name(s)
5-fluorouracil, 5-Fluracil, 5-FU
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
bevacizumab
Other Intervention Name(s)
anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF
Intervention Description
Given IV
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Other Intervention Name(s)
irradiation, radiotherapy, therapy, radiation
Intervention Description
Undergo radiotherapy
Intervention Type
Biological
Intervention Name(s)
filgrastim
Other Intervention Name(s)
G-CSF, Neupogen
Intervention Description
Given subcutaneously
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Objective response rate (CR+PR) assessed using RECIST criteria
Description
The associated 95% confidence interval will be determined.
Time Frame
Up to 9 years
Title
Pattern of failure, described as locoregional, distant, or both
Time Frame
Up to 9 years
Title
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
Title
Progression free survival
Description
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.
Time Frame
From the date of registration to the date of progressive disease or death, assessed up to 9 years
Title
Overall survival
Description
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.
Time Frame
From the date of registration to the date of death, assessed up to 9 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Everett Vokes
Organizational Affiliation
University of Chicago Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Chicago Comprehensive Cancer Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637-1470
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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