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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


Phase 2
18 Years
N/A
Open (Enrolling)
Both
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

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Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Grade 4 Hemorrhage or Any Grade 5 Adverse Event Assessed to be Definitely, Probably, or Possibly Related to Protocol Treatment During the First Year.

Outcome Description:

Estimated using a binomial distribution along with their associated 95% confidence intervals. Graded using the CTCAE version 3.0.

Outcome Time Frame:

From start of treatment to one year.

Safety Issue:

Yes

Principal Investigator

Nancy Lee

Investigator Role:

Principal Investigator

Investigator Affiliation:

American College of Radiology Imaging Network

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00736

NCT ID:

NCT00408694

Start Date:

December 2006

Completion Date:

Related Keywords:

  • 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
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Nasopharyngeal Neoplasms

Name

Location

Roswell Park Cancer Institute Buffalo, New York  14263
Stanford University Stanford, California  94305
Community Medical Center Toms River, New Jersey  08755
Beth Israel Medical Center New York, New York  10003
Brooke Army Medical Center Fort Sam Houston, Texas  78234-6200
Wilford Hall Medical Center Lackland Air Force Base, Texas  78236-5300
Holland Community Hospital Holland, Michigan  49423
Munson Medical Center Traverse City, Michigan  49684
City of Hope Medical Center Duarte, California  91010
Alta Bates Summit Medical Center - Summit Campus Oakland, California  94609
Beebe Medical Center Lewes, Delaware  19958
Mecosta County Medical Center Big Rapids, Michigan  49307
Highland General Hospital Oakland, California  94602
Union Hospital of Cecil County Elkton MD, Maryland  21921
Metro Health Hospital Grand Rapids, Michigan  49506
Solano Radiation Oncology Center Vacaville, California  95687
University of Alabama at Birmingham Birmingham, Alabama  35294-3300
East Bay Radiation Oncology Center Castro Valley, California  94546
Contra Costa Regional Medical Center Martinez, California  94553-3156
Larry G Strieff MD Medical Corporation Oakland, California  94609
University of Pittsburgh Medical Center - Shadyside Hospital Pittsburgh, Pennsylvania  15213-2582
Thomas Jefferson University Hospital Philadelphia, Pennsylvania  19131
UPMC Cancer Center at Jefferson Regional Medical Center Clairton, Pennsylvania  15025
Providence Saint Joseph Medical Center Burbank, California  91505-4866
Memorial Health University Medical Center Savannah, Georgia  31404
M D Anderson Cancer Center Houston, Texas  77030
Froedtert and the Medical College of Wisconsin Milwaukee, Wisconsin  53226
Valley Medical Oncology Consultants-Castro Valley Castro Valley, California  94546
Eden Hospital Medical Center Castro Valley, California  94546
Valley Medical Oncology Consultants-Fremont Fremont, California  94538
Bay Area Breast Surgeons Inc Oakland, California  94609
Bay Area Tumor Institution CCOP Oakland, California  94609
Tom K Lee Inc Oakland, California  94609
Valley Medical Oncology Consultants Pleasanton, California  94588
Valley Care Health System - Pleasanton Pleasanton, California  94588
Doctors Medical Center- JC Robinson Regional Cancer Center San Pablo, California  94806
M D Anderson Cancer Center- Orlando Orlando, Florida  32806
John H Stroger Jr Hospital of Cook County Chicago, Illinois  60612-3785
Grand Rapids Clinical Oncology Program Grand Rapids, Michigan  49503
Saint Mary's Health Care Grand Rapids, Michigan  49503
Spectrum Health at Butterworth Campus Grand Rapids, Michigan  49503
Mercy Health Partners-Hackley Campus Muskegon, Michigan  49442
Saint John's Hospital Springfield, Missouri  65804
Cox Medical Center Springfield, Missouri  65807
Cooper Hospital University Medical Center Camden, New Jersey  08103
Saint Luke's Roosevelt Hospital Center - Saint Luke's Division New York, New York  10025
Pocono Medical Center East Stroudsburg, Pennsylvania  18301
Wheeling Hospital Wheeling, West Virginia  26003
Northeast Radiation Oncology Center Dunmore, Pennsylvania  18512
Radiological Associates of Sacramento Sacramento, California  95816
UMDNJ - New Jersey Medical School Newark, New Jersey  07103
Riverview Hospital Wisconsin Rapids, Wisconsin  54494
Magee-Womens Hospital - University of Pittsburgh Medical Center Pittsburgh, Pennsylvania  15213
Upper Delaware Valley Cancer Center Milford, Pennsylvania  18337
UPMC Cancer Center at UPMC McKeesport McKeesport, Pennsylvania  15132
Washington Hospital Washington, Pennsylvania  15301
Boca Raton Regional Hospital Boca Raton, Florida  33486
Christiana Care Health System-Christiana Hospital Newark, Delaware  19718
Bronson Battle Creek Battle Creek, Michigan  49017
Auburn Radiation Oncology Center Auburn, California  95603
Marshall Radiation Oncology Center Cameron Park, California  95682
Mercy San Juan Medical Center Carmichael, California  95608
Roseville Radiation Oncology Center Roseville, California  95661
Mercy General Hospital Radiation Oncology Center Sacramento, California  95819
Saint Louis Children's Hospital Saint Louis, Missouri  63110
UPMC - Heritage Valley Health System - The Medical Center - Beaver Beaver, Pennsylvania  15009
UPMC Cancer Center at Clarion Hospital Clarion, Pennsylvania  16214
UPMC Cancer Centers - Arnold Palmer Pavilion Greensburg, Pennsylvania  15601
University Pittsburgh Medical Cancer Center-Johnstown Johnstown, Pennsylvania  15901
University of Pittsburgh Medical Center -Moon Township Moon Township, Pennsylvania  15108
University of Pittsburgh Medical Cancer Center - Natrona Heights Natrona Heights, Pennsylvania  15065
Jameson Health System North Campus New Castle, Pennsylvania  16105
University of Pittsburgh Medical Center-Passavant Hospital Pittsburgh, Pennsylvania  15237
University of Pittsburgh Medical Center-Presbyterian Hospital Pittsburgh, Pennsylvania  15213
UPMC Cancer Center at Saint Clair Hospital Pittsburgh, Pennsylvania  15243
Saint Margaret Memorial Hospital Pittsburgh, Pennsylvania  15215
University of Pittsburgh Medical Center Northwest Seneca, Pennsylvania  16346
UPMC Cancer Center - Robert E Eberly Pavilion Uniontown, Pennsylvania  15401