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

October 3, 2022 updated by: Children's Oncology Group

Treatment of Childhood Nasopharyngeal Carcinoma With Neoadjuvant Chemotherapy and Concomitant Chemoradiotherapy: A Groupwide Phase III Study

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

111

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Western Australia
      • Perth, Western Australia, Australia, 6008
        • Princess Margaret Hospital for Children
  • Canada
      • Quebec, Canada, G1V 4G2
        • Centre Hospitalier Universitaire de Quebec
    • Alberta
      • Calgary, Alberta, Canada, T3B 6A8
        • Alberta Children's Hospital
    • British Columbia
      • Vancouver, British Columbia, Canada, V6H 3V4
        • British Columbia Children's Hospital
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3K 6R8
        • IWK Health Centre
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L1
        • Children's Hospital of Eastern Ontario
    • Quebec
      • Montreal, Quebec, Canada, H3T 1C5
        • Centre Hospitalier Universitaire Sainte-Justine
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7N 4H4
        • Saskatoon Cancer Centre
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham Cancer Center
      • Birmingham, Alabama, United States, 35233
        • Children's Hospital of Alabama
    • Arizona
      • Tucson, Arizona, United States, 85719
        • Banner University Medical Center - Tucson
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences
      • Little Rock, Arkansas, United States, 72202-3591
        • Arkansas Children's Hospital
    • California
      • Downey, California, United States, 90242
        • Kaiser Permanente Downey Medical Center
      • Los Angeles, California, United States, 90027
        • Children's Hospital Los Angeles
      • Los Angeles, California, United States, 90095
        • UCLA / Jonsson Comprehensive Cancer Center
      • Los Angeles, California, United States, 90095
        • Mattel Children's Hospital UCLA
      • Madera, California, United States, 93636
        • Valley Children's Hospital
      • Oakland, California, United States, 94611
        • Kaiser Permanente-Oakland
      • Palo Alto, California, United States, 94304
        • Lucile Packard Children's Hospital Stanford University
      • San Francisco, California, United States, 94158
        • UCSF Medical Center-Mission Bay
      • San Francisco, California, United States, 94115
        • UCSF Medical Center-Mount Zion
      • San Francisco, California, United States, 94143
        • UCSF Medical Center-Parnassus
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado
    • Connecticut
      • Farmington, Connecticut, United States, 06030
        • University of Connecticut
      • Hartford, Connecticut, United States, 06106
        • Connecticut Children's Medical Center
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Children's National Medical Center
      • Washington, District of Columbia, United States, 20007
        • MedStar Georgetown University Hospital
    • Florida
      • Fort Myers, Florida, United States, 33901
        • Lee Memorial Health System
      • Hollywood, Florida, United States, 33021
        • Memorial Regional Hospital/Joe DiMaggio Children's Hospital
      • Jacksonville, Florida, United States, 32207
        • Nemours Children's Clinic-Jacksonville
      • Miami, Florida, United States, 33155
        • Nicklaus Children's Hospital
      • Miami, Florida, United States, 33136
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
      • Orlando, Florida, United States, 32806
        • Orlando Health Cancer Institute
      • Orlando, Florida, United States, 32806
        • Arnold Palmer Hospital for Children
      • Saint Petersburg, Florida, United States, 33701
        • Johns Hopkins All Children's Hospital
      • Tampa, Florida, United States, 33607
        • Saint Joseph's Hospital/Children's Hospital-Tampa
      • West Palm Beach, Florida, United States, 33407
        • Saint Mary's Hospital
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital/Winship Cancer Institute
      • Atlanta, Georgia, United States, 30322
        • Children's Healthcare of Atlanta - Egleston
    • Hawaii
      • Honolulu, Hawaii, United States, 96813
        • University of Hawaii Cancer Center
      • Honolulu, Hawaii, United States, 96826
        • Kapiolani Medical Center for Women and Children
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Lurie Children's Hospital-Chicago
      • Springfield, Illinois, United States, 62702
        • Southern Illinois University School of Medicine
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University/Melvin and Bren Simon Cancer Center
      • Indianapolis, Indiana, United States, 46202
        • Riley Hospital for Children
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky/Markey Cancer Center
      • Louisville, Kentucky, United States, 40202
        • Norton Children's Hospital
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane University Health Sciences Center
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University/Sidney Kimmel Cancer Center
      • Baltimore, Maryland, United States, 21215
        • Sinai Hospital of Baltimore
      • Bethesda, Maryland, United States, 20889-5600
        • Walter Reed National Military Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • C S Mott Children's Hospital
      • Detroit, Michigan, United States, 48201
        • Wayne State University/Karmanos Cancer Institute
      • Detroit, Michigan, United States, 48236
        • Ascension Saint John Hospital
      • Grand Rapids, Michigan, United States, 49503
        • Spectrum Health at Butterworth Campus
      • Grand Rapids, Michigan, United States, 49503
        • Helen DeVos Children's Hospital at Spectrum Health
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Hospitals and Clinics
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
      • Saint Louis, Missouri, United States, 63104
        • Cardinal Glennon Children's Medical Center
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
      • Omaha, Nebraska, United States, 68114
        • Children's Hospital and Medical Center of Omaha
    • Nevada
      • Las Vegas, Nevada, United States, 89135
        • Alliance for Childhood Diseases/Cure 4 the Kids Foundation
      • Las Vegas, Nevada, United States, 89169
        • Nevada Cancer Research Foundation NCORP
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
      • Morristown, New Jersey, United States, 07960
        • Morristown Medical Center
      • New Brunswick, New Jersey, United States, 08903
        • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
      • Newark, New Jersey, United States, 07112
        • Newark Beth Israel Medical Center
      • Summit, New Jersey, United States, 07902
        • Overlook Hospital
    • New Mexico
      • Albuquerque, New Mexico, United States, 87102
        • University of New Mexico Cancer Center
    • New York
      • New York, New York, United States, 10032
        • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
      • Rochester, New York, United States, 14642
        • University of Rochester
      • Syracuse, New York, United States, 13210
        • State University of New York Upstate Medical University
      • Valhalla, New York, United States, 10595
        • New York Medical College
    • North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Carolinas Medical Center/Levine Cancer Institute
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • North Dakota
      • Fargo, North Dakota, United States, 58122
        • Sanford Broadway Medical Center
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
      • Cleveland, Ohio, United States, 44106
        • Rainbow Babies and Childrens Hospital
      • Columbus, Ohio, United States, 43205
        • Nationwide Children's Hospital
      • Dayton, Ohio, United States, 45404
        • Dayton Children's Hospital
      • Toledo, Ohio, United States, 43614
        • University of Toledo
      • Toledo, Ohio, United States, 43608
        • Mercy Children's Hospital
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033-0850
        • Penn State Milton S Hershey Medical Center
      • Hershey, Pennsylvania, United States, 17033
        • Penn State Children's Hospital
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
      • Philadelphia, Pennsylvania, United States, 19134
        • Saint Christopher's Hospital for Children
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburgh of UPMC
    • South Carolina
      • Columbia, South Carolina, United States, 29203
        • Prisma Health Richland Hospital
      • Greenville, South Carolina, United States, 29605
        • BI-LO Charities Children's Cancer Center
      • Greenville, South Carolina, United States, 29605
        • Greenville Cancer Treatment Center
    • Tennessee
      • Knoxville, Tennessee, United States, 37916
        • East Tennessee Childrens Hospital
      • Memphis, Tennessee, United States, 38105
        • Saint Jude Children's Research Hospital
    • Texas
      • Corpus Christi, Texas, United States, 78411
        • Driscoll Children's Hospital
      • Dallas, Texas, United States, 75390
        • UT Southwestern/Simmons Cancer Center-Dallas
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
      • San Antonio, Texas, United States, 78229
        • University of Texas Health Science Center at San Antonio
      • San Antonio, Texas, United States, 78229
        • Methodist Children's Hospital of South Texas
    • Utah
      • Salt Lake City, Utah, United States, 84113
        • Primary Children's Hospital
    • Virginia
      • Falls Church, Virginia, United States, 22042
        • Inova Fairfax Hospital
      • Norfolk, Virginia, United States, 23507
        • Children's Hospital of The King's Daughters
    • Washington
      • Spokane, Washington, United States, 99204
        • Providence Sacred Heart Medical Center and Children's Hospital
    • West Virginia
      • Charleston, West Virginia, United States, 25304
        • West Virginia University Charleston Division
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Children's Hospital of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 18 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Stratum I (radiotherapy, chemoprotective agent)
Patients undergo radiotherapy 5 days a week for 8 weeks. Patients also receive amifostine subcutaneously on the same days they undergo radiotherapy.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Amifostine
Given subcutaneously
Other Names:
  • Ethyol
  • WR-2721
  • Ethiofos
  • Gammaphos
  • Amifostine Trihydrate
  • Aminopropylaminoethylthiophosphoric Acid Trihydrate
  • APAETP
  • Cytofos
  • WR 2721
  • WR2721
  • YM-08310
Radiation: Radiation Therapy
Undergo radiotherapy
Other Names:
  • Cancer Radiotherapy
  • ENERGY_TYPE
  • Irradiate
  • Irradiated
  • Irradiation
  • Radiation
  • Radiation Therapy, NOS
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
EXPERIMENTAL: Stratum II (chemotherapy, chemoprotective agent, radiotherapy)
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.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Cisplatin
Given IV
Other Names:
  • CDDP
  • Cis-diamminedichloridoplatinum
  • Cismaplat
  • Cisplatinum
  • Neoplatin
  • Platinol
  • Abiplatin
  • Blastolem
  • Briplatin
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cisplatina
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin
Drug: Fluorouracil
Given IV
Other Names:
  • 5-Fluracil
  • Fluracil
  • 5 Fluorouracil
  • 5 Fluorouracilum
  • 5 FU
  • 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
  • 5-Fluorouracil
  • 5-Fu
  • 5FU
  • AccuSite
  • Carac
  • Fluoro Uracil
  • Fluouracil
  • Flurablastin
  • Fluracedyl
  • Fluril
  • Fluroblastin
  • Ribofluor
  • Ro 2-9757
  • Ro-2-9757
Drug: Amifostine
Given subcutaneously
Other Names:
  • Ethyol
  • WR-2721
  • Ethiofos
  • Gammaphos
  • Amifostine Trihydrate
  • Aminopropylaminoethylthiophosphoric Acid Trihydrate
  • APAETP
  • Cytofos
  • WR 2721
  • WR2721
  • YM-08310
Radiation: Radiation Therapy
Undergo radiotherapy
Other Names:
  • Cancer Radiotherapy
  • ENERGY_TYPE
  • Irradiate
  • Irradiated
  • Irradiation
  • Radiation
  • Radiation Therapy, NOS
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Two Year Event-free Survival (EFS)
Time Frame: 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.
Up to Two Year After Enrollment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Predictive Value of Epstein-Barr Virus (EBV) DNA as Measured by Quantitative Detection at Enrollment on EFS 2 Years After Treatment
Time Frame: At study enrollment
Presence of EBV DNA in serum.
At study enrollment
Prognostic Significance of EBV Viral Load
Time Frame: At study enrollment
Viral load in blood.
At study enrollment
Predictive Value of the Detection of EBV DNA in the Peripheral Blood
Time Frame: 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.
Up to 6 years
Protective Effects of Amifostine Assessed Primarily by Sialometry
Time Frame: At study enrollment
Weight of stimulated saliva production in grams.
At study enrollment
Protective Effects of Amifostine Assessed Primarily by Sialometry: Weight of Unstimulated Saliva Production in Grams.
Time Frame: At study enrollment
Weight of unstimulated saliva production in grams.
At study enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Oncology Group

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

February 20, 2006

Primary Completion (ACTUAL)

December 31, 2014

Study Completion (ACTUAL)

September 30, 2022

Study Registration Dates

First Submitted

January 10, 2006

First Submitted That Met QC Criteria

January 10, 2006

First Posted (ESTIMATE)

January 11, 2006

Study Record Updates

Last Update Posted (ACTUAL)

October 25, 2022

Last Update Submitted That Met QC Criteria

October 3, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ARAR0331 (OTHER: CTEP)
  • U10CA180886 (U.S. NIH Grant/Contract)
  • U10CA098543 (U.S. NIH Grant/Contract)
  • NCI-2009-00412 (REGISTRY: CTRP (Clinical Trial Reporting Program))
  • CDR0000454849
  • COG-ARAR0331

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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