Radiation Therapy, Amifostine, and Chemotherapy in Treating Young Patients With Newly Diagnosed Nasopharyngeal Cancer

Phase 3

Completed

Conditions: Stage II Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7
Stage III Nasopharyngeal Undifferentiated Carcinoma AJCC v7
Stage II Nasopharyngeal Undifferentiated Carcinoma AJCC v7
Stage IV Nasopharyngeal Undifferentiated Carcinoma AJCC v7
Stage I Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7
Stage I Nasopharyngeal Undifferentiated Carcinoma AJCC v7
Stage III Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7
Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7

Interventions: Drug: Amifostine
Other: Laboratory Biomarker Analysis
Drug: Cisplatin
Radiation: Radiation Therapy
Drug: Fluorouracil

Registration Number: NCT00274937

Lead Sponsor: Children's Oncology Group

Brief Summary: This phase III trial is studying how well radiation therapy, amifostine, and chemotherapy work in treating young patients with newly diagnosed nasopharyngeal cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs, such as amifostine, may protect normal cells from the side effects of radiation therapy. 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. Giving radiation therapy together with amifostine and chemotherapy may kill more tumor cells.

Detailed Description: PRIMARY OBJECTIVES:

I. Determine the response rate, overall survival, and event-free survival of children with advanced nasopharyngeal carcinoma who are treated with induction chemotherapy followed by concurrent chemoradiotherapy and amifostine.

SECONDARY OBJECTIVES:

I. Characterize the role of Epstein-Barr virus (EBV) in the pathogenesis of nasopharyngeal carcinoma in children.

II. Investigate the predictive value of the detection of EBV DNA in the peripheral blood of children with nasopharyngeal carcinoma.

III. Determine the incidence of NUT rearrangements in childhood nasopharyngeal carcinoma.

IV. Determine the radioprotective effect of amifostine when given daily prior to radiation therapy.

OUTLINE: This is a nonrandomized, multicenter study. Patients are stratified according to stage of disease (I or IIA \[stratum I\] vs IIB-IV \[stratum II\]).

STRATUM I: Patients undergo radiotherapy 5 days a week for 8 weeks. Patients also receive amifostine subcutaneously on the same days they undergo radiotherapy.

STRATUM II:

INDUCTION THERAPY (weeks 1-9): Patients receive cisplatin IV over 6 hours on day 1 and fluorouracil IV continuously on days 1-4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease proceed to consolidation therapy.

CONSOLIDATION THERAPY (weeks 10-18): Patients undergo radiotherapy and receive amifostine as in stratum I. Patients also receive cisplatin IV over 6 hours on days 1 and 22 (2 courses).

After completion of study treatment, patients are followed periodically for 10 years.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 111

Inclusion Criteria

Histological diagnosis of nasopharyngeal carcinoma WHO type II or III
- Stage I-IV disease
- Newly diagnosed disease
Performance status
- Patients ≤ 16 years of age: Lansky 60-100%
- Patients > 16 years of age: Karnofsky 60-100%
Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min
Creatinine based on age/gender as follows:
- No greater than 0.4 mg/dL (for patients 1 month to < 6 months of age)
- No greater than 0.5 mg/dL (for patients 6 months to < 1 year of age)
- No greater than 0.6 mg/dL (for patients 1-2 years of age)
- No greater than 0.8 mg/dL (for patients < 6 years of age)
- No greater than 1.0mg/dL (for patients 6 to < 10 years of age)
- No greater than 1.2 mg/dL (for patients 10 to < 13 years of age)
- No greater than 1.4 mg/dL (for female patients 13 to ≥ 16 years of age)
- No greater than 1.5 mg/dL (for male patients 13 to < 16 years of age)
- No greater than 1.7 mg/dL (for male patients ≥ 16 years of age)
Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
AST or ALT < 2.5 times ULN for age
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No prior chemotherapy or radiotherapy to the nasopharynx or neck for the treatment of nasopharyngeal carcinoma

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Stratum I (radiotherapy, chemoprotective agent)	Laboratory Biomarker Analysis	Patients undergo radiotherapy 5 days a week for 8 weeks. Patients also receive amifostine subcutaneously on the same days they undergo radiotherapy.
Stratum I (radiotherapy, chemoprotective agent)	Radiation Therapy	Patients undergo radiotherapy 5 days a week for 8 weeks. Patients also receive amifostine subcutaneously on the same days they undergo radiotherapy.
Stratum II (chemotherapy, chemoprotective agent, radiotherapy)	Laboratory Biomarker Analysis	Patients receive cisplatin IV over 6 hours on day 1 and fluorouracil IV continuously on days 1-4. Treatment repeats every 3 weeks for 3 courses. In weeks 10-18, patients undergo radiotherapy and receive amifostine as in stratum I. Patients also receive 3 courses of cisplatin as before.
Stratum II (chemotherapy, chemoprotective agent, radiotherapy)	Radiation Therapy	Patients receive cisplatin IV over 6 hours on day 1 and fluorouracil IV continuously on days 1-4. Treatment repeats every 3 weeks for 3 courses. In weeks 10-18, patients undergo radiotherapy and receive amifostine as in stratum I. Patients also receive 3 courses of cisplatin as before.
Stratum I (radiotherapy, chemoprotective agent)	Amifostine	Patients undergo radiotherapy 5 days a week for 8 weeks. Patients also receive amifostine subcutaneously on the same days they undergo radiotherapy.
Stratum II (chemotherapy, chemoprotective agent, radiotherapy)	Amifostine	Patients receive cisplatin IV over 6 hours on day 1 and fluorouracil IV continuously on days 1-4. Treatment repeats every 3 weeks for 3 courses. In weeks 10-18, patients undergo radiotherapy and receive amifostine as in stratum I. Patients also receive 3 courses of cisplatin as before.
Stratum II (chemotherapy, chemoprotective agent, radiotherapy)	Cisplatin	Patients receive cisplatin IV over 6 hours on day 1 and fluorouracil IV continuously on days 1-4. Treatment repeats every 3 weeks for 3 courses. In weeks 10-18, patients undergo radiotherapy and receive amifostine as in stratum I. Patients also receive 3 courses of cisplatin as before.
Stratum II (chemotherapy, chemoprotective agent, radiotherapy)	Fluorouracil	Patients receive cisplatin IV over 6 hours on day 1 and fluorouracil IV continuously on days 1-4. Treatment repeats every 3 weeks for 3 courses. In weeks 10-18, patients undergo radiotherapy and receive amifostine as in stratum I. Patients also receive 3 courses of cisplatin as before.

Primary Outcome Measures

Name	Time	Method
Two Year Event-free Survival (EFS)	Up to Two Year After Enrollment	The two-year event-free survival will be compared with a standard established from adult oncology data and the results of POG-9486. The two-year Kaplan-Meier estimate of event-free survival will be compared with 70% using a 1-sided test of size 0.05 using the asymptotic distribution of the complementary log-log distribution of the estimate.

Secondary Outcome Measures

Name	Time	Method
Predictive Value of Epstein-Barr Virus (EBV) DNA as Measured by Quantitative Detection at Enrollment on EFS 2 Years After Treatment	At study enrollment	Presence of EBV DNA in serum.
Predictive Value of the Detection of EBV DNA in the Peripheral Blood	Up to 6 years	The prognostic value of the presence of EBV DNA will be assessed using the log-rank test, adjusted by initial stage of disease, if appropriate. The proposed analysis will take place at the analytic endpoint of the clinical trial.
Prognostic Significance of EBV Viral Load	At study enrollment	Viral load in blood.
Protective Effects of Amifostine Assessed Primarily by Sialometry	At study enrollment	Weight of stimulated saliva production in grams.
Protective Effects of Amifostine Assessed Primarily by Sialometry: Weight of Unstimulated Saliva Production in Grams.	At study enrollment	Weight of unstimulated saliva production in grams.

Trial Locations

Locations (109): Driscoll Children's Hospital
🇺🇸
Corpus Christi, Texas, United States
Rainbow Babies and Childrens Hospital
🇺🇸
Cleveland, Ohio, United States
Arkansas Children's Hospital
🇺🇸
Little Rock, Arkansas, United States
Kaiser Permanente-Oakland
🇺🇸
Oakland, California, United States
University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
Mattel Children's Hospital UCLA
🇺🇸
Los Angeles, California, United States
Children's Hospital Los Angeles
🇺🇸
Los Angeles, California, United States
UCLA / Jonsson Comprehensive Cancer Center
🇺🇸
Los Angeles, California, United States
Lucile Packard Children's Hospital Stanford University
🇺🇸
Palo Alto, California, United States
Tulane University Health Sciences Center
🇺🇸
New Orleans, Louisiana, United States
Kaiser Permanente Downey Medical Center
🇺🇸
Downey, California, United States
Helen DeVos Children's Hospital at Spectrum Health
🇺🇸
Grand Rapids, Michigan, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸
Atlanta, Georgia, United States
Cardinal Glennon Children's Medical Center
🇺🇸
Saint Louis, Missouri, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸
Baltimore, Maryland, United States
University of Kentucky/Markey Cancer Center
🇺🇸
Lexington, Kentucky, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
🇺🇸
New York, New York, United States
East Tennessee Childrens Hospital
🇺🇸
Knoxville, Tennessee, United States
Newark Beth Israel Medical Center
🇺🇸
Newark, New Jersey, United States
Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
Dayton Children's Hospital
🇺🇸
Dayton, Ohio, United States
Centre Hospitalier Universitaire de Quebec
🇨🇦
Quebec, Canada
West Virginia University Charleston Division
🇺🇸
Charleston, West Virginia, United States
BI-LO Charities Children's Cancer Center
🇺🇸
Greenville, South Carolina, United States
Alberta Children's Hospital
🇨🇦
Calgary, Alberta, Canada
Centre Hospitalier Universitaire Sainte-Justine
🇨🇦
Montreal, Quebec, Canada
Children's Hospital of The King's Daughters
🇺🇸
Norfolk, Virginia, United States
IWK Health Centre
🇨🇦
Halifax, Nova Scotia, Canada
British Columbia Children's Hospital
🇨🇦
Vancouver, British Columbia, Canada
UCSF Medical Center-Mission Bay
🇺🇸
San Francisco, California, United States
Riley Hospital for Children
🇺🇸
Indianapolis, Indiana, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
Cincinnati Children's Hospital Medical Center
🇺🇸
Cincinnati, Ohio, United States
University of Texas Health Science Center at San Antonio
🇺🇸
San Antonio, Texas, United States
Primary Children's Hospital
🇺🇸
Salt Lake City, Utah, United States
Princess Margaret Hospital for Children
🇦🇺
Perth, Western Australia, Australia
Kapiolani Medical Center for Women and Children
🇺🇸
Honolulu, Hawaii, United States
University of Rochester
🇺🇸
Rochester, New York, United States
University of Mississippi Medical Center
🇺🇸
Jackson, Mississippi, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
University of Alabama at Birmingham Cancer Center
🇺🇸
Birmingham, Alabama, United States
Children's Hospital of Alabama
🇺🇸
Birmingham, Alabama, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸
Detroit, Michigan, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Lee Memorial Health System
🇺🇸
Fort Myers, Florida, United States
University of Hawaii Cancer Center
🇺🇸
Honolulu, Hawaii, United States
Johns Hopkins All Children's Hospital
🇺🇸
Saint Petersburg, Florida, United States
Emory University Hospital/Winship Cancer Institute
🇺🇸
Atlanta, Georgia, United States
Southern Illinois University School of Medicine
🇺🇸
Springfield, Illinois, United States
Morristown Medical Center
🇺🇸
Morristown, New Jersey, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
🇺🇸
New Brunswick, New Jersey, United States
New York Medical College
🇺🇸
Valhalla, New York, United States
University of New Mexico Cancer Center
🇺🇸
Albuquerque, New Mexico, United States
Sanford Broadway Medical Center
🇺🇸
Fargo, North Dakota, United States
Penn State Milton S Hershey Medical Center
🇺🇸
Hershey, Pennsylvania, United States
Penn State Children's Hospital
🇺🇸
Hershey, Pennsylvania, United States
Saint Christopher's Hospital for Children
🇺🇸
Philadelphia, Pennsylvania, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸
Dallas, Texas, United States
Children's Hospital Colorado
🇺🇸
Aurora, Colorado, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
🇺🇸
Tampa, Florida, United States
Mayo Clinic in Rochester
🇺🇸
Rochester, Minnesota, United States
Valley Children's Hospital
🇺🇸
Madera, California, United States
UCSF Medical Center-Mount Zion
🇺🇸
San Francisco, California, United States
UCSF Medical Center-Parnassus
🇺🇸
San Francisco, California, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
🇺🇸
Hollywood, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸
Miami, Florida, United States
Nemours Children's Clinic-Jacksonville
🇺🇸
Jacksonville, Florida, United States
Saint Mary's Hospital
🇺🇸
West Palm Beach, Florida, United States
Lurie Children's Hospital-Chicago
🇺🇸
Chicago, Illinois, United States
Indiana University/Melvin and Bren Simon Cancer Center
🇺🇸
Indianapolis, Indiana, United States
State University of New York Upstate Medical University
🇺🇸
Syracuse, New York, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸
Charlotte, North Carolina, United States
Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Mercy Children's Hospital
🇺🇸
Toledo, Ohio, United States
University of Toledo
🇺🇸
Toledo, Ohio, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸
Pittsburgh, Pennsylvania, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
🇺🇸
Houston, Texas, United States
Cook Children's Medical Center
🇺🇸
Fort Worth, Texas, United States
Methodist Children's Hospital of South Texas
🇺🇸
San Antonio, Texas, United States
Inova Fairfax Hospital
🇺🇸
Falls Church, Virginia, United States
Providence Sacred Heart Medical Center and Children's Hospital
🇺🇸
Spokane, Washington, United States
Nicklaus Children's Hospital
🇺🇸
Miami, Florida, United States
Nationwide Children's Hospital
🇺🇸
Columbus, Ohio, United States
Arnold Palmer Hospital for Children
🇺🇸
Orlando, Florida, United States
Orlando Health Cancer Institute
🇺🇸
Orlando, Florida, United States
Norton Children's Hospital
🇺🇸
Louisville, Kentucky, United States
Children's Mercy Hospitals and Clinics
🇺🇸
Kansas City, Missouri, United States
Banner University Medical Center - Tucson
🇺🇸
Tucson, Arizona, United States
University of Connecticut
🇺🇸
Farmington, Connecticut, United States
Hackensack University Medical Center
🇺🇸
Hackensack, New Jersey, United States
Nevada Cancer Research Foundation NCORP
🇺🇸
Las Vegas, Nevada, United States
Children's National Medical Center
🇺🇸
Washington, District of Columbia, United States
Connecticut Children's Medical Center
🇺🇸
Hartford, Connecticut, United States
Ascension Saint John Hospital
🇺🇸
Detroit, Michigan, United States
Children's Hospital of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Overlook Hospital
🇺🇸
Summit, New Jersey, United States
Sinai Hospital of Baltimore
🇺🇸
Baltimore, Maryland, United States
MedStar Georgetown University Hospital
🇺🇸
Washington, District of Columbia, United States
Prisma Health Richland Hospital
🇺🇸
Columbia, South Carolina, United States
Walter Reed National Military Medical Center
🇺🇸
Bethesda, Maryland, United States
Children's Hospital and Medical Center of Omaha
🇺🇸
Omaha, Nebraska, United States
C S Mott Children's Hospital
🇺🇸
Ann Arbor, Michigan, United States
Spectrum Health at Butterworth Campus
🇺🇸
Grand Rapids, Michigan, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
🇺🇸
Las Vegas, Nevada, United States
University of Nebraska Medical Center
🇺🇸
Omaha, Nebraska, United States
Greenville Cancer Treatment Center
🇺🇸
Greenville, South Carolina, United States
Saint Jude Children's Research Hospital
🇺🇸
Memphis, Tennessee, United States
Saskatoon Cancer Centre
🇨🇦
Saskatoon, Saskatchewan, Canada
Children's Hospital of Eastern Ontario
🇨🇦
Ottawa, Ontario, Canada