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

Tracking Information
First Submitted Date ICMJE	September 13, 2001
First Posted Date ICMJE	January 27, 2003
Last Update Posted Date	February 7, 2013
Study Start Date ICMJE	July 2001
Actual Primary Completion Date	March 2010 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: February 6, 2013)	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 ]
Original Primary Outcome Measures ICMJE	Not Provided
Change History	Complete list of historical versions of study NCT00023959 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: February 6, 2013)	Objective response rate (CR+PR) assessed using RECIST criteria [ Time Frame: Up to 9 years ]The associated 95% confidence interval will be determined.; Pattern of failure, described as locoregional, distant, or both [ Time Frame: 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 ]; 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.; 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.
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Bevacizumab, Fluorouracil, and Hydroxyurea Plus Radiation Therapy in Treating Patients With Advanced Head and Neck Cancer
Official Title ICMJE	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
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.
Study Type ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	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
Intervention ICMJE	Drug: hydroxyurea Given orally Other Names: HU HYD Hydrea Hydroxycarbamide Hydurea; Drug: fluorouracil Given IV Other Names: 5-fluorouracil 5-Fluracil 5-FU; Biological: bevacizumab Given IV Other Names: anti-VEGF humanized monoclonal antibody anti-VEGF monoclonal antibody Avastin rhuMAb VEGF; Radiation: radiation therapy Undergo radiotherapy Other Names: irradiation radiotherapy therapy, radiation; Biological: filgrastim Given subcutaneously Other Names: G-CSF Neupogen; Other: laboratory biomarker analysis Correlative studies
Study Arms	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.; Interventions: Drug: hydroxyurea; Drug: fluorouracil; Biological: bevacizumab; Radiation: radiation therapy; Biological: filgrastim; Other: laboratory biomarker analysis
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: February 6, 2013)	39
Original Enrollment ICMJE	Not Provided
Study Completion Date	Not Provided
Actual Primary Completion Date	March 2010 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00023959
Other Study ID Numbers ICMJE	NCI-2012-02408; 11033B; CDR0000068879 ( Registry Identifier: PDQ (Physician Data Query) )
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	National Cancer Institute (NCI)
Study Sponsor ICMJE	National Cancer Institute (NCI)
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Everett Vokes University of Chicago Comprehensive Cancer Center
PRS Account	National Cancer Institute (NCI)
Verification Date	February 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP