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

Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00274937
• Other study ID #: ARAR0331
• Secondary ID: NCI-2009-00412CD
• Status: Completed
• Phase: Phase 3
• Start date: February 20, 2006
• Est. completion date: September 30, 2022

Study information

• Verified date: October 2022
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 111
• Est. completion date: September 30, 2022
• Est. primary completion date: December 31, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Stage II Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7
• Stage III Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7
• Stage III Nasopharyngeal Undifferentiated Carcinoma AJCC v7
• Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7
• Stage IV Nasopharyngeal Undifferentiated Carcinoma AJCC v7

Intervention

Drug:
• Amifostine
Given subcutaneously
• Cisplatin
Given IV
• Fluorouracil
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Radiation:
• Radiation Therapy
Undergo radiotherapy

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Two Year Event-free Survival (EFS)	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	Predictive Value of Epstein-Barr Virus (EBV) DNA as Measured by Quantitative Detection at Enrollment on EFS 2 Years After Treatment	Presence of EBV DNA in serum.	At study enrollment
Secondary	Prognostic Significance of EBV Viral Load	Viral load in blood.	At study enrollment
Secondary	Predictive Value of the Detection of EBV DNA in the Peripheral Blood	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
Secondary	Protective Effects of Amifostine Assessed Primarily by Sialometry	Weight of stimulated saliva production in grams.	At study enrollment
Secondary	Protective Effects of Amifostine Assessed Primarily by Sialometry: Weight of Unstimulated Saliva Production in Grams.	Weight of unstimulated saliva production in grams.	At study enrollment

External Links

•   Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive