Bevacizumab, Cisplatin, Radiation Therapy, and Fluorouracil in Treating Patients With Stage IIB, Stage III, Stage IVA, or Stage IVB Nasopharyngeal Cancer
This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00408694
First received: December 6, 2006
Last updated: March 1, 2013
Last verified: March 2013
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Purpose
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 | Intervention | 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 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: 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 |
Resource links provided by NLM:
Further study details as provided by National Cancer Institute (NCI):
Primary Outcome Measures:
- 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. ] [ Designated as safety issue: Yes ]Estimated using a binomial distribution along with their associated 95% confidence intervals. Graded using the CTCAE version 3.0.
Secondary Outcome Measures:
- 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: From day 366 to end of follow-up. ] [ Designated as safety issue: Yes ]Estimated using a binomial distribution along with their associated 95% confidence intervals. Graded using the CTCAE version 3.0.
- Patient Tolerability to Each Component (Concurrent and Adjuvant) of the Protocol Treatment Regimen [ Time Frame: 109 From start of treatment to end of treatment (approximately day 109). ] [ Designated as safety issue: Yes ]Estimated using a binomial distribution along with their associated 95% confidence intervals. Evaluated in terms of protocol treatment delivery. Measured by the percentage of patients who received 2 or more cycles of cisplatin (CDDP) and bevacizumab (BV) during concurrent treatment with RT and RT scored by the study chair as no variation or minor variation. Tolerability for the adjuvant component will be measured by the percentage of patients who received 2 or more cycles of CDDP and 5-FU and BV during the adjuvant treatment phase.
- Death During or Within 30 Days of Discontinuation of Protocol Treatment. [ Time Frame: From discontinuation of protocol treatment to 30 days after. ] [ Designated as safety issue: Yes ]
- One- and Two-year Distant Metastases-free Rates [ Time Frame: From registration to two years. ] [ Designated as safety issue: No ]Estimated using the cumulative incidence method. Estimated along with their associated 95% confidence intervals.
- One- and Two-year Loco-regional Progression-free Rates [ Time Frame: From registration to two years. ] [ Designated as safety issue: No ]Estimated using the cumulative incidence method. Estimated along with their associated 95% confidence intervals.
- One- and Two-year Progression-free Survival Rates [ Time Frame: From registration to two years. ] [ Designated as safety issue: No ]Estimated using the Kaplan-Meier method. Estimated along with their associated 95% confidence intervals.
- One- and Two-year Overall Survival Rates [ Time Frame: From registration to two years. ] [ Designated as safety issue: No ]Estimated using the Kaplan-Meier method. Estimated along with their associated 95% confidence intervals.
| Enrollment: | 46 |
| Study Start Date: | December 2006 |
| Primary Completion Date: | December 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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, 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:
Radiation: intensity-modulated radiation therapy
Undergo IMRT
Other Name: IMRT
Biological: bevacizumab
Given IV
Other Names:
Drug: cisplatin
Given IV
Other Names:
Drug: fluorouracil
Given IV
Other Names:
|
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, 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| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00408694
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Hide Study LocationsLocations
| United States, Alabama | |
| University of Alabama at Birmingham | |
| Birmingham, Alabama, United States, 35293 | |
| United States, California | |
| Auburn Radiation Oncology Center | |
| Auburn, California, United States, 95603 | |
| Providence Saint Joseph Medical Center | |
| Burbank, California, United States, 91505 | |
| Marshall Radiation Oncology Center | |
| Cameron Park, California, United States, 95682 | |
| Mercy San Juan Medical Center | |
| Carmichael, California, United States, 95608 | |
| Valley Medical Oncology Consultants-Castro Valley | |
| 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 | |
| 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 | |
| Tom K Lee Inc | |
| Oakland, California, United States, 94609 | |
| Bay Area Tumor Institution CCOP | |
| Oakland, California, United States, 94609 | |
| Larry G Strieff MD Medical Corporation | |
| Oakland, California, United States, 94609 | |
| Bay Area Breast Surgeons Inc | |
| Oakland, California, United States, 94609 | |
| Alta Bates Summit Medical Center - Summit Campus | |
| Oakland, California, United States, 94609 | |
| Highland General Hospital | |
| Oakland, California, United States, 94602 | |
| Valley Medical Oncology Consultants | |
| Pleasanton, California, United States, 94588 | |
| Valley Care Health System - Pleasanton | |
| Pleasanton, California, United States, 94588 | |
| Roseville Radiation Oncology Center | |
| 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 | |
| Stanford, California, United States, 94305 | |
| Solano Radiation Oncology Center | |
| 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 | |
| M D Anderson Cancer Center- Orlando | |
| 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 MD, Maryland, United States, 21921 | |
| United States, Michigan | |
| Bronson Battle Creek | |
| Battle Creek, Michigan, United States, 49017 | |
| Mecosta County Medical Center | |
| Big Rapids, Michigan, United States, 49307 | |
| Saint Mary's Health Care | |
| Grand Rapids, Michigan, United States, 49503 | |
| Spectrum Health at Butterworth Campus | |
| Grand Rapids, Michigan, United States, 49503 | |
| Grand Rapids Clinical Oncology Program | |
| 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 | |
| Cox Medical Center | |
| Springfield, Missouri, United States, 65807 | |
| Saint John's Hospital | |
| Springfield, Missouri, United States, 65804 | |
| 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 | |
| Saint Luke's Roosevelt Hospital Center - Saint Luke's Division | |
| New York, New York, United States, 10025 | |
| Beth Israel Medical Center | |
| New York, New York, United States, 10003 | |
| United States, Pennsylvania | |
| UPMC - Heritage Valley Health System - The Medical Center - 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 | |
| University Pittsburgh Medical Cancer Center-Johnstown | |
| 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 | |
| University of Pittsburgh Medical Center -Moon Township | |
| Moon Township, Pennsylvania, United States, 15108 | |
| University of Pittsburgh Medical Cancer Center - Natrona Heights | |
| Natrona Heights, Pennsylvania, United States, 15065 | |
| Jameson Health System North Campus | |
| New Castle, Pennsylvania, United States, 16105 | |
| Thomas Jefferson University Hospital | |
| Philadelphia, Pennsylvania, United States, 19107 | |
| University of Pittsburgh Medical Center-Passavant Hospital | |
| Pittsburgh, Pennsylvania, United States, 15237 | |
| Magee-Womens Hospital - University of Pittsburgh Medical Center | |
| Pittsburgh, Pennsylvania, United States, 15213 | |
| University of Pittsburgh Medical Center - Shadyside Hospital | |
| Pittsburgh, Pennsylvania, United States, 15232 | |
| University of Pittsburgh Medical Center-Presbyterian Hospital | |
| Pittsburgh, Pennsylvania, United States, 15213 | |
| UPMC Cancer Center at Saint Clair Hospital | |
| Pittsburgh, Pennsylvania, United States, 15243 | |
| Saint Margaret Memorial Hospital | |
| Pittsburgh, Pennsylvania, United States, 15215 | |
| University of Pittsburgh Medical Center Northwest | |
| Seneca, Pennsylvania, United States, 16346 | |
| UPMC Cancer Center - 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 AFB, 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
Investigators
| Principal Investigator: | Nancy Lee | American College of Radiology Imaging Network |
More Information
Additional Information:
No publications provided by National Cancer Institute (NCI)
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00408694 History of Changes |
| Obsolete Identifiers: | NCT00707096 |
| Other Study ID Numbers: | NCI-2009-00736, RTOG-0615, U10CA021661, CDR0000518526 |
| Study First Received: | December 6, 2006 |
| Results First Received: | March 1, 2013 |
| Last Updated: | March 1, 2013 |
| Health Authority: | United States: Food and Drug Administration |
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 |
Antibodies Antibodies, Monoclonal Fluorouracil Bevacizumab Cisplatin Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Radiation-Sensitizing Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic Immunosuppressive Agents |
ClinicalTrials.gov processed this record on May 19, 2013