Bevacizumab, Cisplatin, Radiation Therapy, and Fluorouracil in Treating Patients With Stage IIB, Stage III, Stage IVA, or Stage IVB Nasopharyngeal Cancer

A Phase II Study of Concurrent Chemoradiotherapy Using Three-Dimensional Conformal Radiotherapy (3D-CRT) or Intensity-Modulated Radiation Therapy (IMRT) + Bevacizumab (BV) for Locally or Regionally Advanced Nasopharyngeal Cancer

This phase II trial is studying how well giving bevacizumab together with cisplatin, radiation therapy, and fluorouracil works in treating patients with stage IIB, stage III, stage IVA, or stage IVB nasopharyngeal cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of nasopharyngeal cancer by blocking blood flow to the tumor. Drugs used in chemotherapy, such as cisplatin and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving bevacizumab together with chemotherapy and radiation therapy may kill more tumor cells.

Study Overview

• Status: Completed
• Conditions: Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IV Nasopharyngeal Undifferentiated Carcinoma AJCC v7; Stage II Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage III Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage III Nasopharyngeal Undifferentiated Carcinoma AJCC v7
• Intervention / Treatment: Drug: Cisplatin; Radiation: Intensity-Modulated Radiation Therapy; Biological: Bevacizumab; Drug: Fluorouracil; Radiation: 3-Dimensional Conformal Radiation Therapy

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the safety and tolerability of bevacizumab and chemoradiotherapy comprising cisplatin and radiotherapy followed by adjuvant therapy comprising cisplatin, fluorouracil, and bevacizumab in patients with stage IIB-IVB nasopharyngeal cancer.

SECONDARY OBJECTIVES:

I. Determine the 1- and 2-year rates of locoregional progression-free in patients treated with this regimen.

II. Determine the 1- and 2-year rates of distant metastases-free in patients treated with this regimen.

III. Determine the 1- and 2-year rates of progression-free and overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

BEVACIZUMAB AND CHEMORADIOTHERAPY: Patients receive bevacizumab IV over 30-90 minutes and cisplatin IV over 20-30 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning in week 1, patients also undergo three-dimensional conformal radiotherapy or intensity-modulated radiotherapy once daily 5 days a week for a total of 33 fractions.

ADJUVANT THERAPY: Beginning in week 10, patients receive fluorouracil IV continuously over 96 hours on days 1-4, cisplatin IV over 20-30 minutes on day 1 OR days 1 and 2, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network-Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill University Department of Oncology
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham Cancer Center
  • California
    • Auburn, California, United States, 95603
      • Sutter Cancer Centers Radiation Oncology Services-Auburn
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    • Cameron Park, California, United States, 95682
      • Sutter Cancer Centers Radiation Oncology Services-Cameron Park
    • Carmichael, California, United States, 95608
      • Mercy San Juan Medical Center
    • Castro Valley, California, United States, 94546
      • Eden Hospital Medical Center
    • Castro Valley, California, United States, 94546
      • East Bay Radiation Oncology Center
    • Castro Valley, California, United States, 94546
      • Valley Medical Oncology Consultants-Castro Valley
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Emeryville, California, United States, 94608
      • Bay Area Breast Surgeons Inc
    • Fremont, California, United States, 94538
      • Valley Medical Oncology Consultants-Fremont
    • Martinez, California, United States, 94553-3156
      • Contra Costa Regional Medical Center
    • Oakland, California, United States, 94609
      • Alta Bates Summit Medical Center - Summit Campus
    • Oakland, California, United States, 94609
      • Hematology and Oncology Associates-Oakland
    • Oakland, California, United States, 94602
      • Highland General Hospital
    • Oakland, California, United States, 94609
      • Tom K Lee Inc
    • Oakland, California, United States, 94609
      • Bay Area Tumor Institute
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Institute Palo Alto
    • Pleasanton, California, United States, 94588
      • Valley Care Health System - Pleasanton
    • Pleasanton, California, United States, 94588
      • Valley Medical Oncology Consultants
    • Roseville, California, United States, 95661
      • Sutter Cancer Centers Radiation Oncology Services-Roseville
    • Sacramento, California, United States, 95816
      • Sutter Medical Center Sacramento
    • Sacramento, California, United States, 95819
      • Mercy General Hospital Radiation Oncology Center
    • San Pablo, California, United States, 94806
      • Doctors Medical Center- JC Robinson Regional Cancer Center
    • Vacaville, California, United States, 95687
      • Sutter Cancer Centers Radiation Oncology Services-Vacaville
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Beebe Medical Center
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Boca Raton Regional Hospital
    • Jacksonville, Florida, United States, 32207
      • Baptist MD Anderson Cancer Center
    • Jacksonville, Florida, United States, 32258
      • Baptist Medical Center South
    • Jacksonville, Florida, United States, 32207
      • Integrated Community Oncology Network-Southside Cancer Center
    • Jacksonville Beach, Florida, United States, 32250
      • Integrated Community Oncology Network-Florida Cancer Center Beaches
    • Miami, Florida, United States, 33176
      • Baptist Hospital of Miami
    • Orange Park, Florida, United States, 32073
      • 21st Century Oncology-Orange Park
    • Orlando, Florida, United States, 32806
      • UF Cancer Center at Orlando Health
    • Palatka, Florida, United States, 32177
      • 21st Century Oncology-Palatka
    • Saint Augustine, Florida, United States, 32086
      • Integrated Community Oncology Network-Flager Cancer Center
  • Georgia
    • Savannah, Georgia, United States, 31404
      • Memorial University Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • John H Stroger Jr Hospital of Cook County
  • Indiana
    • Anderson, Indiana, United States, 46016
      • Saint Vincent Anderson Regional Hospital/Cancer Center
  • Maryland
    • Elkton, Maryland, United States, 21921
      • Union Hospital of Cecil County
  • Michigan
    • Battle Creek, Michigan, United States, 49017
      • Bronson Battle Creek
    • Big Rapids, Michigan, United States, 49307
      • Spectrum Health Big Rapids Hospital
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health at Butterworth Campus
    • Grand Rapids, Michigan, United States, 49503
      • Mercy Health Saint Mary's
    • Grand Rapids, Michigan, United States, 49503
      • Cancer Research Consortium of West Michigan NCORP
    • Holland, Michigan, United States, 49423
      • Holland Community Hospital
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49001
      • Borgess Medical Center
    • Muskegon, Michigan, United States, 49442
      • Mercy Health Partners-Hackley Campus
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • Wyoming, Michigan, United States, 49519
      • Metro Health Hospital
  • Mississippi
    • Pascagoula, Mississippi, United States, 39581
      • Singing River Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis Children's Hospital
    • Saint Peters, Missouri, United States, 63376
      • Siteman Cancer Center at Saint Peters Hospital
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
    • Mount Holly, New Jersey, United States, 08060
      • Virtua Memorial
    • New Brunswick, New Jersey, United States, 08901
      • Saint Peter's University Hospital
    • Newark, New Jersey, United States, 07101
      • Rutgers New Jersey Medical School
    • Toms River, New Jersey, United States, 08755
      • Community Medical Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10003
      • Beth Israel Medical Center
    • New York, New York, United States, 10025
      • Saint Luke's Roosevelt Hospital Center - Saint Luke's Division
  • North Carolina
    • Rutherfordton, North Carolina, United States, 28139
      • Rutherford Hospital
  • Ohio
    • Akron, Ohio, United States, 44304
      • Summa Akron City Hospital/Cooper Cancer Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Beaver, Pennsylvania, United States, 15009
      • UPMC-Heritage Valley Health System Beaver
    • Clarion, Pennsylvania, United States, 16214
      • UPMC Cancer Center at Clarion Hospital
    • Dunmore, Pennsylvania, United States, 18512
      • Northeast Radiation Oncology Center
    • East Stroudsburg, Pennsylvania, United States, 18301
      • Pocono Medical Center
    • Greensburg, Pennsylvania, United States, 15601
      • UPMC Cancer Centers - Arnold Palmer Pavilion
    • Johnstown, Pennsylvania, United States, 15901
      • UPMC-Johnstown/John P. Murtha Regional Cancer Center
    • McKeesport, Pennsylvania, United States, 15132
      • UPMC Cancer Center at UPMC McKeesport
    • Milford, Pennsylvania, United States, 18337
      • Upper Delaware Valley Cancer Center
    • Moon, Pennsylvania, United States, 15108
      • UPMC-Coraopolis/Heritage Valley Radiation Oncology
    • Natrona Heights, Pennsylvania, United States, 15065
      • UPMC Cancer Center-Natrona Heights
    • New Castle, Pennsylvania, United States, 16105
      • UPMC Jameson
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Philadelphia, Pennsylvania, United States, 19103
      • Radiation Therapy Oncology Group
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC-Magee Womens Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC-Shadyside Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC-Presbyterian Hospital
    • Pittsburgh, Pennsylvania, United States, 15215
      • UPMC-Saint Margaret
    • Pittsburgh, Pennsylvania, United States, 15236
      • UPMC Jefferson Regional Radiation Oncology
    • Pittsburgh, Pennsylvania, United States, 15237
      • UPMC-Passavant Hospital
    • Pittsburgh, Pennsylvania, United States, 15243
      • UPMC-Saint Clair Hospital Cancer Center
    • Seneca, Pennsylvania, United States, 16346
      • UPMC Cancer Center at UPMC Northwest
    • Uniontown, Pennsylvania, United States, 15401
      • UPMC Uniontown Hospital Radiation Oncology
    • Washington, Pennsylvania, United States, 15301
      • UPMC Washington Hospital Radiation Oncology
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health Hospital
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Center
  • Texas
    • Fort Sam Houston, Texas, United States, 78234
      • Brooke Army Medical Center
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
    • Lackland Air Force Base, Texas, United States, 78236
      • Wilford Hall Medical Center
  • West Virginia
    • Wheeling, West Virginia, United States, 26003
      • Wheeling Hospital/Schiffler Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert and The Medical College of Wisconsin
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Aspirus UW Cancer Center

Participation Criteria

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 confirmed cancer of the nasopharynx based on biopsy of a primary lesion and/or lymph nodes

  • Histologic WHO types I-IIb/III

• Stage IIB-IVB disease

  • No T1-2, N1 disease in which node positivity is based on the presence of retropharyngeal lymph nodes
• No distant metastases
• Zubrod performance status 0-1
• WBC ? 4,000/mm?
• Hemoglobin ? 9.0 g/dL
• Platelet count ? 100,000/mm?
• Absolute neutrophil count ? 1,500/mm?
• INR ? 1.5
• aPTT ? 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase ? 1.5 times ULN
• ALT and AST ? 1.5 times ULN
• Bilirubin ? 1.5 times ULN
• Creatinine ? 1.5 mg/dL OR creatinine clearance ? 55 mL/min

• Urine protein:creatinine (UPC) ratio < 1.0

  • If UPC > 0.5, 24-hour urine protein must be < 1,000 mg
• Hearing loss primarily sensorineural in nature and requiring a hearing aid or intervention that interferes in a clinically significant way with activities of daily living allowed
• Conductive hearing loss from tumor-related otitis media is allowed

• No severe, active comorbidity, including any of the following:

  • Ongoing bleeding diathesis, hemorrhagic disorder, or coagulopathy within the past 6 months
  • Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
  • Esophageal varices, nonhealing wound, nonhealing ulcer, or bone fracture within the past 6 months
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within the past 30 days
  • Unstable angina and/or congestive heart failure or peripheral vascular disease requiring hospitalization within the past 12 months
  • Major medical or psychiatric illness that, in the opinion of the study investigator, would preclude study compliance
  • Active, untreated infection and/or acute bacterial or fungal infection requiring intravenous antibiotics
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
  • History of significant weight loss (> 15% from baseline)
  • History of arterial thromboembolic events
  • Acquired immune deficiency syndrome
  • Transmural myocardial infarction
  • Cerebrovascular accident
  • Transient ischemic attack
  • Any other cardiac condition that, in the opinion of the investigator, would preclude study compliance
• No gross hemoptysis or hematemesis, defined as bright red blood of ? 1 teaspoon per coughing episode, within the last 4 weeks (incidental blood mixed with phlegm allowed)
• No other invasive malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the breast, oral cavity, or cervix
• Nutritional and physical condition considered suitable for study treatment
• No significant traumatic injury within the past 4 weeks
• No history of allergic reaction to the study drugs
• No baseline blood pressure > 150/100 mm Hg
• No peripheral neuropathy ? grade 2
• Not pregnant or nursing
• Negative serum pregnancy test
• Fertile patients must use effective contraception during and for ? 6 months after completion of study treatment
• At least 10 days since prior and no concurrent dipyridamole, ticlopidine, clopidogrel bisulfate, cilostazol, warfarin, heparin, daily treatment with acetylsalicylic acid (> 325 mg/day), or nonsteroidal anti-inflammatory medications known to inhibit platelet function

• No prior head and neck surgery of the primary tumor or lymph nodes except for incisional or excisional biopsies

  • More than 15 days since prior biopsies
• More than 1 week since prior fine-needle aspirations or placement of percutaneous gastrostomy tube
• More than 4 weeks since prior major surgical procedures
• No prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• No prior bevacizumab or other vascular endothelial growth factor-targeting agents

• No prior systemic chemotherapy for the study cancer

  • Prior chemotherapy for a different cancer allowed
• No concurrent hematologic growth factors (e.g. filgrastim [G-CSF], darbepoetin alfa, epoetin alfa) during study chemoradiotherapy
• No concurrent prophylactic growth factors for neutropenia during study adjuvant therapy
• No concurrent prophylactic amifostine or pilocarpine
• No other concurrent experimental therapeutic cancer treatments

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (bevacizumab, cisplatin, fluorouracil, IMRT, 3D-CRT); BEVACIZUMAB AND CHEMORADIOTHERAPY: Patients receive bevacizumab IV over 30-90 minutes and cisplatin IV over 20-30 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning in week 1, patients also undergo three-dimensional conformal radiotherapy or intensity-modulated radiotherapy once daily 5 days a week for a total of 33 fractions. ADJUVANT THERAPY: Beginning in week 10, patients receive fluorouracil IV continuously over 96 hours on days 1-4, cisplatin IV over 20-30 minutes on day 1 OR days 1 and 2, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.

Drug: Cisplatin; Given IV; Other Names: CDDP; Cis-diamminedichloridoplatinum; Cismaplat; Cisplatinum; Neoplatin; Platinol; Abiplatin; Blastolem; Briplatin; Cis-diammine-dichloroplatinum; Cis-diamminedichloro Platinum (II); Cis-diamminedichloroplatinum; Cis-dichloroammine Platinum (II); Cis-platinous Diamine Dichloride; Cis-platinum; Cis-platinum II; Cis-platinum II Diamine Dichloride; Cisplatina; Cisplatyl; Citoplatino; Citosin; Cysplatyna; DDP; Lederplatin; Metaplatin; Peyrone's Chloride; Peyrone's Salt; Placis; Plastistil; Platamine; Platiblastin; Platiblastin-S; Platinex; Platinol- AQ; Platinol-AQ; Platinol-AQ VHA Plus; Platinoxan; Platinum; Platinum Diamminodichloride; Platiran; Platistin; Platosin; Radiation: Intensity-Modulated Radiation Therapy; Undergo IMRT; Other Names: IMRT; Intensity Modulated RT; Intensity-Modulated Radiotherapy; Biological: Bevacizumab; Given IV; Other Names: Avastin; Anti-VEGF; Anti-VEGF Humanized Monoclonal Antibody; Anti-VEGF rhuMAb; Bevacizumab Biosimilar BEVZ92; Bevacizumab Biosimilar BI 695502; Bevacizumab Biosimilar CBT 124; Bevacizumab Biosimilar FKB238; Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer; Recombinant Humanized Anti-VEGF Monoclonal Antibody; rhuMab-VEGF; BEVACIZUMAB, LICENSE HOLDER UNSPECIFIED; Drug: Fluorouracil; Given IV; Other Names: 5-FU; 5-Fluracil; Fluracil; 5-Fluoro-2,4(1H, 3H)-pyrimidinedione; 5-Fluorouracil; AccuSite; Carac; Fluoro Uracil; Fluouracil; Flurablastin; Fluracedyl; Fluril; Fluroblastin; Ribofluor; Ro 2-9757; Ro-2-9757; Radiation: 3-Dimensional Conformal Radiation Therapy; Undergo 3D-CRT; Other Names: 3-dimensional radiation therapy; 3D CONFORMAL RADIATION THERAPY; 3D CRT; 3D-CRT; Conformal Therapy; Radiation Conformal Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With a Grade 4 Hemorrhage or Any Grade 5 Adverse Event Assessed to be Definitely, Probably, or Possibly Related to Protocol Treatment During the First Year.	Estimated using a binomial distribution along with the 95% confidence interval. Adverse events (AE) are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.	From start of treatment to one year.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With Grade 4 Hemorrhage or Any Grade 5 Adverse Event Assessed to be Definitely, Probably, or Possibly Related to Protocol Treatment After the First Year.	Estimated using a binomial distribution along with the 95% confidence interval. Adverse events (AE) are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.	Analysis occurs after all patients have been on study for at least 2 years. Patients are followed from day 366 to death or study termination whichever occurs first, up to 3.6 years.
Patient Tolerability to Each Component (Concurrent and Adjuvant) of the Protocol Treatment Regimen	Evaluated in terms of protocol treatment delivery. For concurrent treatment, measured by the percentage of patients who received 2 or more cycles of cisplatin (CDDP) and bevacizumab (BV) during concurrent treatment with radiation therapy(RT) and who had RT scored by the study chair as no variation or minor variation. For adjuvant treatment, measured by the percentage of patients who received 2 or more cycles of CDDP and 5-FU and BV during the adjuvant treatment phase. Estimated using a binomial distribution along with their associated 95% confidence intervals.	From start of treatment to end of treatment (approximately day 109).
Death During or Within 30 Days of Discontinuation of Protocol Treatment.	The percentage of patients dying during protocol treatment or within 30 days after the end of treatment. Estimated using a binomial distribution along with associated 95% confidence interval.	From start of treatment to 30 days after end of treatment (treatment ends approximately day 109).
One- and Two-year Distant Metastases-free Rates	Distant metastasis is defined as clear evidence of distant metastases (lung, bone, brain, etc.); biopsy is recommended where possible. Distant metastasis-free rate estimated by cumulative incidence method with death considered a competing risk.	From registration to two years
One- and Two-year Loco-regional Progression-free Rates	Loco-regional progression is defined as an estimated increase in the size of the tumor (product of the perpendicular diameters of the two largest dimensions) of greater than 25%, taking as reference the smallest value of all previous measurements or appearance of new areas of malignant disease. Local-regional progression-free rate estimated by cumulative incidence with death considered a competing risk.	Analysis occurs after all patients have been on study for at least 2 years. Patients are followed from study registration to death or study termination whichever occurs first, up to 3.6 years.
One- and Two-year Progression-free Survival Rates	Progression-free survival rate estimated by Kaplan-Meier method along with 95% confidence interval. An event is loco-regional or distant progression, or death due to any cause. Loco-regional progression is defined as an estimated increase in the size of the tumor (product of the perpendicular diameters of the two largest dimensions) of greater than 25%, taking as reference the smallest value of all previous measurements or appearance of new areas of malignant disease. Distant progression is defined as distant metastases.	Analysis occurs after all patients have been on study for at least 2 years. Patients are followed from study registration to death or study termination whichever occurs first, up to 3.6 years.
One- and Two-year Overall Survival Rates	Overall survival rate estimated by Kaplan-Meier method along with 95% confidence interval. An event is death due to any cause.	Analysis occurs after all patients have been on study for at least 2 years. Patients are followed from study registration to death or study termination whichever occurs first, up to 3.6 years.
Percentage of Patients With Other Grade 3-5 Adverse Events Assessed to be Definitely, Probably, or Possibly Related to Protocol Treatment	Estimated using a binomial distribution along with the 95% confidence interval. Adverse events (AE) are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.	Analysis occurs after all patients have been on study for at least 2 years. Patients are followed from start of treatment to death or study termination whichever occurs first, up to 3.6 years.

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: Radiation Therapy Oncology Group
• Investigators: Principal Investigator: Nancy Lee, Radiation Therapy Oncology Group

Publications and helpful links

General Publications

• Lee NY, Zhang Q, Pfister DG, Kim J, Garden AS, Mechalakos J, Hu K, Le QT, Colevas AD, Glisson BS, Chan AT, Ang KK. Addition of bevacizumab to standard chemoradiation for locoregionally advanced nasopharyngeal carcinoma (RTOG 0615): a phase 2 multi-institutional trial. Lancet Oncol. 2012 Feb;13(2):172-80. doi: 10.1016/S1470-2045(11)70303-5. Epub 2011 Dec 15.

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2006
• Primary Completion (Actual): December 15, 2011
• Study Completion (Actual): December 15, 2011

Study Registration Dates

• First Submitted: December 6, 2006
• First Submitted That Met QC Criteria: December 6, 2006
• First Posted (Estimate): December 7, 2006

Study Record Updates

• Last Update Posted (Actual): January 30, 2018
• Last Update Submitted That Met QC Criteria: January 4, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Neoplasms, Squamous Cell; Carcinoma; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Carcinoma, Squamous Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antibodies; Cisplatin; Fluorouracil; Immunoglobulins; Bevacizumab; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Immunoglobulin G; Endothelial Growth Factors
• Other Study ID Numbers: NCI-2009-00736 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA021661 (U.S. NIH Grant/Contract); RTOG-0615 (Other Identifier: CTEP); CDR0000518526; RTOG 0615 (Other Identifier: Radiation Therapy Oncology Group)