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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00274937
First received: January 10, 2006
Last updated: February 28, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Stage I Lymphoepithelioma of the Nasopharynx
Stage I Squamous Cell Carcinoma of the Nasopharynx
Stage II Lymphoepithelioma of the Nasopharynx
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
Drug: amifostine trihydrate
Drug: fluorouracil
Drug: cisplatin
Other: laboratory biomarker analysis
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Childhood Nasopharyngeal Carcinoma With Neoadjuvant Chemotherapy and Concomitant Chemoradiotherapy: A Groupwide Phase III Study

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Disease-free survival (EFS) [ Time Frame: At 2 years ] [ Designated as safety issue: No ]
    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%. Confidence intervals for the estimated two year EFS will be provided. The one-sample one-sided log-rank test comparing the observed data with the hypothesized model of size 0.05 will be used to assess whether the data are consistent with the target model. The method of Lan and DeMets will be used to derive the p-values for testing procedure.


Secondary Outcome Measures:
  • Predictive value of Epstein-Barr virus (EBV) DNA as measured by quantitative detection at 2 years after treatment [ Time Frame: Not Provided ] [ Designated as safety issue: No ]
  • Prognostic significance of EBV viral load [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    The assessment of the prognostic significance of EBV changes and risk for clinical events will be conducted using survival analysis techniques.

  • Predictive value of the detection of EBV DNA in the peripheral blood [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    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.

  • Protective effects of amifostine assessed primarily by sialometry [ Time Frame: At baseline and up to 12 weeks after completion of radiotherapy ] [ Designated as safety issue: No ]
    The difference in the total amount of saliva collected at study enrollment will be subtracted from the total amount of saliva collected at the end of treatment, after adjustment for the collection time at each time point. A Wilcoxon test logrank test of size 0.05 of the null hypothesis of 0 median change in amount of saliva collected will be used to assess the protective effect of amifostine.


Enrollment: 111
Study Start Date: February 2006
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Stratum I (radiotherapy, chemoprotective agent)
Patients undergo radiation therapy 5 days a week for 8 weeks. Patients also receive amifostine trihydrate subcutaneously on the same days they undergo radiation therapy.
Drug: amifostine trihydrate
Given subcutaneously
Other Names:
  • ethiofos
  • Ethyol
  • gammaphos
  • WR-2721
Other: laboratory biomarker analysis
Correlative studies
Radiation: radiation therapy
Undergo radiotherapy
Other Names:
  • irradiation
  • radiotherapy
  • 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 radiation therapy and receive amifostine trihydrate as in stratum I. Patients also receive 3 courses of cisplatin as before.
Drug: amifostine trihydrate
Given subcutaneously
Other Names:
  • ethiofos
  • Ethyol
  • gammaphos
  • WR-2721
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Other: laboratory biomarker analysis
Correlative studies
Radiation: radiation therapy
Undergo radiotherapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation

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.

  Eligibility

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00274937

  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Arizona
University of Arizona Health Sciences Center
Tucson, Arizona, United States, 85724
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Southern California Permanente Medical Group
Downey, California, United States, 90242
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
David Geffen School of Medicine at UCLA
Los Angeles, California, United States, 90095
Children's Hospital Central California
Madera, California, United States, 93636-8762
Kaiser Permanente-Oakland
Oakland, California, United States, 94611
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States, 94304
University of California San Francisco Medical Center-Parnassus
San Francisco, California, United States, 94143
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, Connecticut
Connecticut Children's Medical Center
Hartford, Connecticut, United States, 06106
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
Lombardi Comprehensive Cancer Center at Georgetown University
Washington, District of Columbia, United States, 20057
United States, Florida
Lee Memorial Health System
Fort Myers, Florida, United States, 33901
Memorial Healthcare System - Joe DiMaggio Children's Hospital
Hollywood, Florida, United States, 33021
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States, 33136
Miami Children's Hospital
Miami, Florida, United States, 33155
M D Anderson Cancer Center- Orlando
Orlando, Florida, United States, 32806
All Children's Hospital
Saint Petersburg, Florida, United States, 33701
Saint Joseph Children's Hospital of Tampa
Tampa, Florida, United States, 33607
United States, Georgia
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States, 30322
United States, Hawaii
University of Hawaii
Honolulu, Hawaii, United States, 96813
United States, Illinois
Childrens Memorial Hospital
Chicago, Illinois, United States, 60614
Southern Illinois University
Springfield, Illinois, United States, 62702
United States, Indiana
Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
Kosair Children's Hospital
Louisville, Kentucky, United States, 40202
United States, Louisiana
Tulane University Health Sciences Center
New Orleans, Louisiana, United States, 70112
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287-8936
Sinai Hospital of Baltimore
Baltimore, Maryland, United States, 21215
Walter Reed National Military Medical Center
Bethesda, Maryland, United States, 20889-5600
United States, Michigan
C S Mott Children's Hospital
Ann Arbor, Michigan, United States, 48109
Wayne State University
Detroit, Michigan, United States, 48202
Saint John Hospital and Medical Center
Detroit, Michigan, United States, 48236
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids, Michigan, United States, 49503
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
United States, Missouri
The Childrens Mercy Hospital
Kansas City, Missouri, United States, 64108
Cardinal Glennon Children's Medical Center
Saint Louis, Missouri, United States, 63104
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Nebraska
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, United States, 68114
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, Nevada
Nevada Cancer Research Foundation CCOP
Las Vegas, Nevada, United States, 89106
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
UMDNJ - Robert Wood Johnson University Hospital
New Brunswick, New Jersey, United States, 08903
Newark Beth Israel Medical Center
Newark, New Jersey, United States, 07112
Overlook Hospital
Summit, New Jersey, United States, 07902
United States, New Mexico
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States, 87106
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
University of Rochester
Rochester, New York, United States, 14642
State University of New York Upstate Medical University
Syracuse, New York, United States, 13210
New York Medical College
Valhalla, New York, United States, 10595
United States, North Carolina
Carolinas Medical Center
Charlotte, North Carolina, United States, 28203
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, North Dakota
Sanford Medical Center-Fargo
Fargo, North Dakota, United States, 58122
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, United States, 44106
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
The Children's Medical Center of Dayton
Dayton, Ohio, United States, 45404
Mercy Children's Hospital
Toledo, Ohio, United States, 43608
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Penn State Hershey Children's Hospital
Hershey, Pennsylvania, United States, 17033
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, United States, 19134
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, South Carolina
Palmetto Health Richland
Columbia, South Carolina, United States, 29203
Greenville Cancer Treatment Center
Greenville, South Carolina, United States, 29605
United States, Tennessee
East Tennessee Childrens Hospital
Knoxville, Tennessee, United States, 37916
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
Driscoll Children's Hospital
Corpus Christi, Texas, United States, 78411
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
Cook Children's Medical Center
Fort Worth, Texas, United States, 76104
Baylor College of Medicine
Houston, Texas, United States, 77030
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States, 78229
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229-3900
United States, Utah
Primary Children's Medical Center
Salt Lake City, Utah, United States, 84113
United States, Virginia
Inova Fairfax Hospital
Falls Church, Virginia, United States, 22042
Childrens Hospital-King's Daughters
Norfolk, Virginia, United States, 23507
United States, Washington
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, United States, 99204
United States, West Virginia
West Virginia University Charleston
Charleston, West Virginia, United States, 25304
United States, Wisconsin
Midwest Children's Cancer Center
Milwaukee, Wisconsin, United States, 53226
Australia, Western Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia, 6008
Canada, Alberta
Alberta Children's Hospital
Calgary, Alberta, Canada, T3B 6A8
Canada, British Columbia
British Columbia Children's Hospital
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Nova Scotia
IWK Health Centre
Halifax, Nova Scotia, Canada, B3J 3G9
Canada, Ontario
Children's Hospital of Eastern Ontario
Ottawa, Ontario, Canada, K1H 8L1
Canada, Quebec
Hospital Sainte-Justine
Montreal, Quebec, Canada, H3T 1C5
Centre Hospitalier Universitaire de Quebec
Ste-Foy, Quebec, Canada, G1V 4G2
Canada, Saskatchewan
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, Canada, S7N 4H4
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Carlos Rodriguez-Galindo, MD Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00274937     History of Changes
Other Study ID Numbers: ARAR0331, NCI-2009-00412, COG-ARAR0331, CDR0000454849, U10CA098543
Study First Received: January 10, 2006
Last Updated: February 28, 2014
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
Cisplatin
Fluorouracil
Amifostine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Radiation-Protective Agents
Protective Agents
Physiological Effects of Drugs
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on July 31, 2014