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

Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00408694
• Other study ID #: NCI-2009-00736
• Secondary ID: NCI-2009-00736RT
• Status: Completed
• Phase: Phase 2
• First received: December 6, 2006
• Last updated: January 4, 2018
• Start date: December 13, 2006
• Est. completion date: December 15, 2011

Study information

• Verified date: January 2018
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00707096

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: December 15, 2011
• Est. primary completion date: December 15, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Nasopharyngeal Neoplasms
• 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

Intervention

Radiation:
• 3-Dimensional Conformal Radiation Therapy
Undergo 3D-CRT

Biological:
• Bevacizumab
Given IV

Drug:
• Cisplatin
Given IV
• Fluorouracil
Given IV

Radiation:
• Intensity-Modulated Radiation Therapy
Undergo IMRT

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	London Regional Cancer Program	London	Ontario
Canada	McGill University Department of Oncology	Montreal	Quebec
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario
United States	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio
United States	AnMed Health Hospital	Anderson	South Carolina
United States	Saint Vincent Anderson Regional Hospital/Cancer Center	Anderson	Indiana
United States	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	UPMC-Heritage Valley Health System Beaver	Beaver	Pennsylvania
United States	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Boca Raton Regional Hospital	Boca Raton	Florida
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California
United States	Mercy San Juan Medical Center	Carmichael	California
United States	East Bay Radiation Oncology Center	Castro Valley	California
United States	Eden Hospital Medical Center	Castro Valley	California
United States	Valley Medical Oncology Consultants-Castro Valley	Castro Valley	California
United States	Medical University of South Carolina	Charleston	South Carolina
United States	John H Stroger Jr Hospital of Cook County	Chicago	Illinois
United States	UPMC Cancer Center at Clarion Hospital	Clarion	Pennsylvania
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Northeast Radiation Oncology Center	Dunmore	Pennsylvania
United States	Pocono Medical Center	East Stroudsburg	Pennsylvania
United States	Union Hospital of Cecil County	Elkton	Maryland
United States	Bay Area Breast Surgeons Inc	Emeryville	California
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Valley Medical Oncology Consultants-Fremont	Fremont	California
United States	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan
United States	Mercy Health Saint Mary's	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	UPMC Cancer Centers - Arnold Palmer Pavilion	Greensburg	Pennsylvania
United States	Holland Community Hospital	Holland	Michigan
United States	M D Anderson Cancer Center	Houston	Texas
United States	Baptist MD Anderson Cancer Center	Jacksonville	Florida
United States	Baptist Medical Center South	Jacksonville	Florida
United States	Integrated Community Oncology Network-Southside Cancer Center	Jacksonville	Florida
United States	Integrated Community Oncology Network-Florida Cancer Center Beaches	Jacksonville Beach	Florida
United States	UPMC-Johnstown/John P. Murtha Regional Cancer Center	Johnstown	Pennsylvania
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Wilford Hall Medical Center	Lackland Air Force Base	Texas
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Beebe Medical Center	Lewes	Delaware
United States	Contra Costa Regional Medical Center	Martinez	California
United States	UPMC Cancer Center at UPMC McKeesport	McKeesport	Pennsylvania
United States	Baptist Hospital of Miami	Miami	Florida
United States	Upper Delaware Valley Cancer Center	Milford	Pennsylvania
United States	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	UPMC-Coraopolis/Heritage Valley Radiation Oncology	Moon	Pennsylvania
United States	Virtua Memorial	Mount Holly	New Jersey
United States	Mercy Health Partners-Hackley Campus	Muskegon	Michigan
United States	UPMC Cancer Center-Natrona Heights	Natrona Heights	Pennsylvania
United States	Saint Peter's University Hospital	New Brunswick	New Jersey
United States	UPMC Jameson	New Castle	Pennsylvania
United States	Beth Israel Medical Center	New York	New York
United States	Saint Luke's Roosevelt Hospital Center - Saint Luke's Division	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Rutgers New Jersey Medical School	Newark	New Jersey
United States	Alta Bates Summit Medical Center - Summit Campus	Oakland	California
United States	Bay Area Tumor Institute	Oakland	California
United States	Hematology and Oncology Associates-Oakland	Oakland	California
United States	Highland General Hospital	Oakland	California
United States	Tom K Lee Inc	Oakland	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	21st Century Oncology-Orange Park	Orange Park	Florida
United States	UF Cancer Center at Orlando Health	Orlando	Florida
United States	21st Century Oncology-Palatka	Palatka	Florida
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Singing River Hospital	Pascagoula	Mississippi
United States	Radiation Therapy Oncology Group	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	UPMC Jefferson Regional Radiation Oncology	Pittsburgh	Pennsylvania
United States	UPMC-Magee Womens Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Passavant Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Presbyterian Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Saint Clair Hospital Cancer Center	Pittsburgh	Pennsylvania
United States	UPMC-Saint Margaret	Pittsburgh	Pennsylvania
United States	UPMC-Shadyside Hospital	Pittsburgh	Pennsylvania
United States	Valley Care Health System - Pleasanton	Pleasanton	California
United States	Valley Medical Oncology Consultants	Pleasanton	California
United States	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	Mercy General Hospital Radiation Oncology Center	Sacramento	California
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	Integrated Community Oncology Network-Flager Cancer Center	Saint Augustine	Florida
United States	Saint Louis Children's Hospital	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Doctors Medical Center- JC Robinson Regional Cancer Center	San Pablo	California
United States	Memorial University Medical Center	Savannah	Georgia
United States	UPMC Cancer Center at UPMC Northwest	Seneca	Pennsylvania
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Community Medical Center	Toms River	New Jersey
United States	Munson Medical Center	Traverse City	Michigan
United States	UPMC Uniontown Hospital Radiation Oncology	Uniontown	Pennsylvania
United States	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California
United States	UPMC Washington Hospital Radiation Oncology	Washington	Pennsylvania
United States	Wheeling Hospital/Schiffler Cancer Center	Wheeling	West Virginia
United States	Aspirus UW Cancer Center	Wisconsin Rapids	Wisconsin
United States	Metro Health Hospital	Wyoming	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	Radiation Therapy Oncology Group

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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).
Secondary	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).
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.