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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00408694
Recruitment Status : Completed
First Posted : December 7, 2006
Results First Posted : April 18, 2013
Last Update Posted : December 11, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment Phase
Stage II Squamous Cell Carcinoma of the Nasopharynx Stage III Lymphoepithelioma of the Nasopharynx Stage III Squamous Cell Carcinoma of the Nasopharynx Stage IV Lymphoepithelioma of the Nasopharynx Stage IV Squamous Cell Carcinoma of the Nasopharynx Radiation: 3-dimensional conformal radiation therapy Radiation: intensity-modulated radiation therapy Biological: bevacizumab Drug: cisplatin Drug: fluorouracil Phase 2

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 Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 46 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : December 2006
Primary Completion Date : December 2011
Study Completion Date : December 2011

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

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.

Radiation: 3-dimensional conformal radiation therapy
Undergo 3D-CRT
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Radiation: intensity-modulated radiation therapy
Undergo IMRT
Other Name: IMRT
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU


Outcome Measures

Primary Outcome Measures :
  1. Percentage of Patients Wiht 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. [ Time Frame: From start of treatment to one 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.


Secondary Outcome Measures :
  1. 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. [ Time Frame: 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. ]
    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.

  2. Patient Tolerability to Each Component (Concurrent and Adjuvant) of the Protocol Treatment Regimen [ Time Frame: From start of treatment to end of treatment (approximately day 109). ]
    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.

  3. Death During or Within 30 Days of Discontinuation of Protocol Treatment. [ Time Frame: From start of treatment to 30 days after end of treatment (treatment ends approximately day 109). ]
    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.

  4. One- and Two-year Distant Metastases-free Rates [ Time Frame: 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. ]
    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.

  5. One- and Two-year Loco-regional Progression-free Rates [ Time Frame: 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. ]
    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.

  6. One- and Two-year Progression-free Survival Rates [ Time Frame: 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. ]
    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.

  7. One- and Two-year Overall Survival Rates [ Time Frame: 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. ]
    Overall survival rate estimated by Kaplan-Meier method along with 95% confidence interval. An event is death due to any cause.

  8. Percentage of Patients With Other Grade 3-5 Adverse Events Assessed to be Definitely, Probably, or Possibly Related to Protocol Treatment [ Time Frame: 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. ]
    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.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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/mm³
  • Hemoglobin ≥ 9.0 g/dL
  • Platelet count ≥ 100,000/mm³
  • Absolute neutrophil count ≥ 1,500/mm³
  • 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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00408694


  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Sutter Cancer Centers Radiation Oncology Services-Auburn
Auburn, California, United States, 95603
Providence Saint Joseph Medical Center/Disney Family Cancer Center
Burbank, California, United States, 91505
Sutter Cancer Centers Radiation Oncology Services-Cameron Park
Cameron Park, California, United States, 95682
Mercy San Juan Medical Center
Carmichael, California, United States, 95608
East Bay Radiation Oncology Center
Castro Valley, California, United States, 94546
Eden Hospital Medical Center
Castro Valley, California, United States, 94546
Valley Medical Oncology Consultants-Castro Valley
Castro Valley, California, United States, 94546
City of Hope Medical Center
Duarte, California, United States, 91010
Valley Medical Oncology Consultants-Fremont
Fremont, California, United States, 94538
Contra Costa Regional Medical Center
Martinez, California, United States, 94553-3156
Highland General Hospital
Oakland, California, United States, 94602
Alta Bates Summit Medical Center - Summit Campus
Oakland, California, United States, 94609
Bay Area Breast Surgeons Inc
Oakland, California, United States, 94609
Bay Area Tumor Institute CCOP
Oakland, California, United States, 94609
Larry G Strieff MD Medical Corporation
Oakland, California, United States, 94609
Tom K Lee Inc
Oakland, California, United States, 94609
Valley Care Health System - Pleasanton
Pleasanton, California, United States, 94588
Valley Medical Oncology Consultants
Pleasanton, California, United States, 94588
Sutter Cancer Centers Radiation Oncology Services-Roseville
Roseville, California, United States, 95661
Radiological Associates of Sacramento
Sacramento, California, United States, 95815
Mercy General Hospital Radiation Oncology Center
Sacramento, California, United States, 95819
Doctors Medical Center- JC Robinson Regional Cancer Center
San Pablo, California, United States, 94806
Stanford University Hospitals and Clinics
Stanford, California, United States, 94305
Sutter Cancer Centers Radiation Oncology Services-Vacaville
Vacaville, California, United States, 95687
United States, Delaware
Beebe Medical Center
Lewes, Delaware, United States, 19958
Christiana Care Health System-Christiana Hospital
Newark, Delaware, United States, 19718
United States, Florida
Boca Raton Regional Hospital
Boca Raton, Florida, United States, 33486
UF Cancer Center at Orlando Health
Orlando, Florida, United States, 32806
United States, Georgia
Memorial Health University Medical Center
Savannah, Georgia, United States, 31403
United States, Illinois
John H Stroger Jr Hospital of Cook County
Chicago, Illinois, United States, 60612-3785
United States, Maryland
Union Hospital of Cecil County
Elkton, Maryland, United States, 21921
United States, Michigan
Bronson Battle Creek
Battle Creek, Michigan, United States, 49017
Spectrum Health Big Rapids Hospital
Big Rapids, Michigan, United States, 49307
Grand Rapids Clinical Oncology Program
Grand Rapids, Michigan, United States, 49503
Mercy Health Saint Mary's
Grand Rapids, Michigan, United States, 49503
Spectrum Health at Butterworth Campus
Grand Rapids, Michigan, United States, 49503
Holland Community Hospital
Holland, Michigan, United States, 49423
Mercy Health Partners-Hackley Campus
Muskegon, Michigan, United States, 49442
Munson Medical Center
Traverse City, Michigan, United States, 49684
Metro Health Hospital
Wyoming, Michigan, United States, 49519
United States, Missouri
Saint Louis Children's Hospital
Saint Louis, Missouri, United States, 63110
Mercy Hospital Springfield
Springfield, Missouri, United States, 65804
CoxHealth South Hospital
Springfield, Missouri, United States, 65807
United States, New Jersey
Cooper Hospital University Medical Center
Camden, New Jersey, United States, 08103
UMDNJ - New Jersey Medical School
Newark, New Jersey, United States, 07103
Community Medical Center
Toms River, New Jersey, United States, 08755
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Beth Israel Medical Center
New York, New York, United States, 10003
Saint Luke's Roosevelt Hospital Center - Saint Luke's Division
New York, New York, United States, 10025
United States, Pennsylvania
UPMC - HVHS Cancer Center at Heritage Valley Beaver
Beaver, Pennsylvania, United States, 15009
UPMC Cancer Center at Jefferson Regional Medical Center
Clairton, Pennsylvania, United States, 15025
UPMC Cancer Center at Clarion Hospital
Clarion, Pennsylvania, United States, 16214
Northeast Radiation Oncology Center
Dunmore, Pennsylvania, United States, 18512
Pocono Medical Center
East Stroudsburg, Pennsylvania, United States, 18301
UPMC Cancer Centers - Arnold Palmer Pavilion
Greensburg, Pennsylvania, United States, 15601
UPMC-Johnstown/John P. Murtha Regional Cancer Center
Johnstown, Pennsylvania, United States, 15901
UPMC Cancer Center at UPMC McKeesport
McKeesport, Pennsylvania, United States, 15132
Upper Delaware Valley Cancer Center
Milford, Pennsylvania, United States, 18337
UPMC-Coraopolis/Heritage Valley Radiation Oncology
Moon Township, Pennsylvania, United States, 15108
UPMC Cancer Center-Natrona Heights
Natrona Heights, Pennsylvania, United States, 15065
Jameson Health System North Campus
New Castle, Pennsylvania, United States, 16105
Radiation Therapy Oncology Group
Philadelphia, Pennsylvania, United States, 19103
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States, 19107
Magee-Womens Hospital of UPMC
Pittsburgh, Pennsylvania, United States, 15213
University of Pittsburgh Medical Center-Presbyterian Hospital
Pittsburgh, Pennsylvania, United States, 15213
UPMC-Saint Margaret
Pittsburgh, Pennsylvania, United States, 15215
UPMC-Shadyside Hospital
Pittsburgh, Pennsylvania, United States, 15232
UPMC-Passavant Hospital
Pittsburgh, Pennsylvania, United States, 15237
UPMC-Saint Clair Hospital Cancer Center
Pittsburgh, Pennsylvania, United States, 15243
UPMC Cancer Center at UPMC Northwest
Seneca, Pennsylvania, United States, 16346
UPMC-Uniontown/Robert E. Eberly Pavilion
Uniontown, Pennsylvania, United States, 15401
Washington Hospital
Washington, Pennsylvania, United States, 15301
United States, Texas
Brooke Army Medical Center
Fort Sam Houston, Texas, United States, 78234
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Wilford Hall Medical Center
Lackland Air Force Base, Texas, United States, 78236
United States, West Virginia
Wheeling Hospital
Wheeling, West Virginia, United States, 26003
United States, Wisconsin
Froedtert and the Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Riverview Hospital
Wisconsin Rapids, Wisconsin, United States, 54494
Canada, Ontario
London Regional Cancer Program
London, Ontario, Canada, N6A 4L6
University Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
McGill University Department of Oncology
Montreal, Quebec, Canada, H2W 1S6
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Nancy Lee Radiation Therapy Oncology Group
More Information

Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00408694     History of Changes
Obsolete Identifiers: NCT00707096
Other Study ID Numbers: NCI-2009-00736
NCI-2009-00736 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
RTOG-0615
CDR0000518526
RTOG 0615 ( Other Identifier: Radiation Therapy Oncology Group )
RTOG-0615 ( Other Identifier: CTEP )
U10CA021661 ( U.S. NIH Grant/Contract )
First Posted: December 7, 2006    Key Record Dates
Results First Posted: April 18, 2013
Last Update Posted: December 11, 2017
Last Verified: October 2017

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Nasopharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Cisplatin
Bevacizumab
Fluorouracil
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Immunologic Factors
Antimetabolites
Molecular Mechanisms of Pharmacological Action