Clinical trial NCT00408694: Bevacizumab, Cisplatin, Radiation Therapy, and Fluorouracil in Treating Patients With Stage IIB, Stage III, Stage IVA, or Stage IVB Nasopharyngeal Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7
Stage IV Nasopharyngeal Undifferentiated Carcinoma AJCC v7
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: Radiation Therapy Oncology Group
First posted: 2006-12-07
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: From start of treatment to one year.
Secondary outcomes:
measure: 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.
timeFrame: 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.
measure: Patient Tolerability to Each Component (Concurrent and Adjuvant) of the Protocol Treatment Regimen
timeFrame: From start of treatment to end of treatment (approximately day 109).
measure: Death During or Within 30 Days of Discontinuation of Protocol Treatment.
timeFrame: From start of treatment to 30 days after end of treatment (treatment ends approximately day 109).
measure: One- and Two-year Distant Metastases-free Rates
timeFrame: From registration to two years
measure: One- and Two-year Loco-regional Progression-free Rates
timeFrame: 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.
measure: One- and Two-year Progression-free Survival Rates
timeFrame: 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.
measure: One- and Two-year Overall Survival Rates
timeFrame: 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.
measure: Percentage of Patients With Other Grade 3-5 Adverse Events Assessed to be Definitely, Probably, or Possibly Related to Protocol Treatment
timeFrame: 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.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Cancer Center
state: Alabama
city: Auburn
country: United States
facility: Sutter Cancer Centers Radiation Oncology Services-Auburn
state: California
city: Burbank
country: United States
facility: Providence Saint Joseph Medical Center/Disney Family Cancer Center
state: California
city: Cameron Park
country: United States
facility: Sutter Cancer Centers Radiation Oncology Services-Cameron Park
state: California
city: Carmichael
country: United States
facility: Mercy San Juan Medical Center
state: California
city: Castro Valley
country: United States
facility: East Bay Radiation Oncology Center
state: California
city: Castro Valley
country: United States
facility: Eden Hospital Medical Center
state: California
city: Castro Valley
country: United States
facility: Valley Medical Oncology Consultants-Castro Valley
state: California
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Emeryville
country: United States
facility: Bay Area Breast Surgeons Inc
state: California
city: Fremont
country: United States
facility: Valley Medical Oncology Consultants-Fremont
state: California
city: Martinez
country: United States
facility: Contra Costa Regional Medical Center
state: California
city: Oakland
country: United States
facility: Highland General Hospital
state: California
city: Oakland
country: United States
facility: Alta Bates Summit Medical Center - Summit Campus
state: California
city: Oakland
country: United States
facility: Bay Area Tumor Institute
state: California
city: Oakland
country: United States
facility: Hematology and Oncology Associates-Oakland
state: California
city: Oakland
country: United States
facility: Tom K Lee Inc
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Institute Palo Alto
state: California
city: Pleasanton
country: United States
facility: Valley Care Health System - Pleasanton
state: California
city: Pleasanton
country: United States
facility: Valley Medical Oncology Consultants
state: California
city: Roseville
country: United States
facility: Sutter Cancer Centers Radiation Oncology Services-Roseville
state: California
city: Sacramento
country: United States
facility: Sutter Medical Center Sacramento
state: California
city: Sacramento
country: United States
facility: Mercy General Hospital Radiation Oncology Center
state: California
city: San Pablo
country: United States
facility: Doctors Medical Center- JC Robinson Regional Cancer Center
state: California
city: Vacaville
country: United States
facility: Sutter Cancer Centers Radiation Oncology Services-Vacaville
state: California
city: Lewes
country: United States
facility: Beebe Medical Center
state: Delaware
city: Newark
country: United States
facility: Christiana Care Health System-Christiana Hospital
state: Delaware
city: Boca Raton
country: United States
facility: Boca Raton Regional Hospital
state: Florida
city: Jacksonville Beach
country: United States
facility: Integrated Community Oncology Network-Florida Cancer Center Beaches
state: Florida
city: Jacksonville
country: United States
facility: Baptist MD Anderson Cancer Center
state: Florida
city: Jacksonville
country: United States
facility: Integrated Community Oncology Network-Southside Cancer Center
state: Florida
city: Jacksonville
country: United States
facility: Baptist Medical Center South
state: Florida
city: Miami
country: United States
facility: Baptist Hospital of Miami
state: Florida
city: Orange Park
country: United States
facility: 21st Century Oncology-Orange Park
state: Florida
city: Orlando
country: United States
facility: UF Cancer Center at Orlando Health
state: Florida
city: Palatka
country: United States
facility: 21st Century Oncology-Palatka
state: Florida
city: Saint Augustine
country: United States
facility: Integrated Community Oncology Network-Flager Cancer Center
state: Florida
city: Savannah
country: United States
facility: Memorial University Medical Center
state: Georgia
city: Chicago
country: United States
facility: John H Stroger Jr Hospital of Cook County
state: Illinois
city: Anderson
country: United States
facility: Saint Vincent Anderson Regional Hospital/Cancer Center
state: Indiana
city: Elkton
country: United States
facility: Union Hospital of Cecil County
state: Maryland
city: Battle Creek
country: United States
facility: Bronson Battle Creek
state: Michigan
city: Big Rapids
country: United States
facility: Spectrum Health Big Rapids Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Cancer Research Consortium of West Michigan NCORP
state: Michigan
city: Grand Rapids
country: United States
facility: Mercy Health Saint Mary's
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health at Butterworth Campus
state: Michigan
city: Holland
country: United States
facility: Holland Community Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: Borgess Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Muskegon
country: United States
facility: Mercy Health Partners-Hackley Campus
state: Michigan
city: Traverse City
country: United States
facility: Munson Medical Center
state: Michigan
city: Wyoming
country: United States
facility: Metro Health Hospital
state: Michigan
city: Pascagoula
country: United States
facility: Singing River Hospital
state: Mississippi
city: Saint Louis
country: United States
facility: Saint Louis Children's Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Peters
country: United States
facility: Siteman Cancer Center at Saint Peters Hospital
state: Missouri
city: Springfield
country: United States
facility: Mercy Hospital Springfield
state: Missouri
city: Springfield
country: United States
facility: CoxHealth South Hospital
state: Missouri
city: Las Vegas
country: United States
facility: University Medical Center of Southern Nevada
state: Nevada
city: Camden
country: United States
facility: Cooper Hospital University Medical Center
state: New Jersey
city: Mount Holly
country: United States
facility: Virtua Memorial
state: New Jersey
city: New Brunswick
country: United States
facility: Saint Peter's University Hospital
state: New Jersey
city: Newark
country: United States
facility: Rutgers New Jersey Medical School
state: New Jersey
city: Toms River
country: United States
facility: Community Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: New York
country: United States
facility: Saint Luke's Roosevelt Hospital Center - Saint Luke's Division
state: New York
city: Rutherfordton
country: United States
facility: Rutherford Hospital
state: North Carolina
city: Akron
country: United States
facility: Summa Akron City Hospital/Cooper Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Beaver
country: United States
facility: UPMC-Heritage Valley Health System Beaver
state: Pennsylvania
city: Clarion
country: United States
facility: UPMC Cancer Center at Clarion Hospital
state: Pennsylvania
city: Dunmore
country: United States
facility: Northeast Radiation Oncology Center
state: Pennsylvania
city: East Stroudsburg
country: United States
facility: Pocono Medical Center
state: Pennsylvania
city: Greensburg
country: United States
facility: UPMC Cancer Centers - Arnold Palmer Pavilion
state: Pennsylvania
city: Johnstown
country: United States
facility: UPMC-Johnstown/John P. Murtha Regional Cancer Center
state: Pennsylvania
city: McKeesport
country: United States
facility: UPMC Cancer Center at UPMC McKeesport
state: Pennsylvania
city: Milford
country: United States
facility: Upper Delaware Valley Cancer Center
state: Pennsylvania
city: Moon
country: United States
facility: UPMC-Coraopolis/Heritage Valley Radiation Oncology
state: Pennsylvania
city: Natrona Heights
country: United States
facility: UPMC Cancer Center-Natrona Heights
state: Pennsylvania
city: New Castle
country: United States
facility: UPMC Jameson
state: Pennsylvania
city: Philadelphia
country: United States
facility: Radiation Therapy Oncology Group
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC-Magee Womens Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC-Presbyterian Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC-Saint Margaret
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC-Shadyside Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Jefferson Regional Radiation Oncology
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC-Passavant Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC-Saint Clair Hospital Cancer Center
state: Pennsylvania
city: Seneca
country: United States
facility: UPMC Cancer Center at UPMC Northwest
state: Pennsylvania
city: Uniontown
country: United States
facility: UPMC Uniontown Hospital Radiation Oncology
state: Pennsylvania
city: Washington
country: United States
facility: UPMC Washington Hospital Radiation Oncology
state: Pennsylvania
city: Anderson
country: United States
facility: AnMed Health Hospital
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Medical Center
state: South Carolina
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Lackland Air Force Base
country: United States
facility: Wilford Hall Medical Center
state: Texas
city: Wheeling
country: United States
facility: Wheeling Hospital/Schiffler Cancer Center
state: West Virginia
city: Milwaukee
country: United States
facility: Froedtert and the Medical College of Wisconsin
state: Wisconsin
city: Wisconsin Rapids
country: United States
facility: Aspirus UW Cancer Center
state: Wisconsin
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Toronto
country: Canada
facility: University Health Network-Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University Department of Oncology
state: Quebec
Study officials:
affiliation: Radiation Therapy Oncology Group
name: Nancy Lee
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.