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

Condition(s) targeted: Head and Neck Cancer; Radiation Toxicity

Intervention: amifostine trihydrate (Drug); cisplatin (Drug); fluorouracil (Drug); radiation therapy (Radiation)

Phase: Phase 3

Status: Recruiting

Sponsored by: Children's Oncology Group

Official(s) and/or principal investigator(s):
Carlos Rodriguez-Galindo, MD, Study Chair, Affiliation: St. Jude Children's Research Hospital

RATIONALE: 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.

PURPOSE: This phase III trial is studying how well radiation therapy, amifostine, and chemotherapy work in treating young patients with newly diagnosed nasopharyngeal cancer.

Official title: Treatment of Childhood Nasopharyngeal Carcinoma With Neoadjuvant Chemotherapy and Concomitant Chemoradiotherapy

Study design: Treatment, Non-Randomized

Primary outcome:

Disease-free survival at 2 years after treatment

Response rate at 12 weeks after induction

Secondary outcome: Predictive value of Epstein-Barr virus (EBV) DNA as measured by quantitative detection at 2 years after treatment

Detailed description: OBJECTIVES:

Primary

- 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

- Characterize the role of Epstein-Barr virus (EBV) in the pathogenesis of nasopharyngeal

carcinoma in children.

- Investigate the predictive value of the detection of EBV DNA in the peripheral blood of

children with nasopharyngeal carcinoma.

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

- 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.

PROJECTED ACCRUAL: A total of 160 patients will be accrued for this study.

Minimum age: N/A. Maximum age: 18 Years. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS:

- Histological diagnosis of nasopharyngeal carcinoma WHO type II or III

- Stage I-IV disease

- Newly diagnosed disease

PATIENT CHARACTERISTICS:

- 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 OR

- 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. 0 mg/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

PRIOR CONCURRENT THERAPY:

- No prior chemotherapy or radiotherapy to the nasopharynx or neck for the treatment of

nasopharyngeal carcinoma

Centre Hospitalier Universitaire de Quebec, Quebec G1V 4G2, Canada; Recruiting
Bruno Michon, Phone: 418-656-4141X47191

UAB Comprehensive Cancer Center, Birmingham, Alabama 35294, United States; Recruiting
Clinical Trials Office - UAB Comprehensive Cancer Center, Phone: 205-934-0309

Alberta Children's Hospital, Calgary, Alberta T3B 6A8, Canada; Recruiting
Douglas R. Strother, Phone: 403-955-7272

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, United States; Recruiting
Clinical Trial Office - Arkansas Cancer Research Center at Uni, Phone: 501-686-8274

Children's & Women's Hospital of British Columbia, Vancouver, British Columbia V6H 3V4, Canada; Recruiting
Mason C. Bond, Phone: 604-875-2322

Children's Hospital Central California, Madera, California 93638-8762, United States; Recruiting
Vonda L. Crouse, Phone: 559-353-5480

Kaiser Permanente Medical Center - Oakland, Sacramento, California 95825, United States; Recruiting
Vincent Kiley, Phone: 916-474-2326

Southern California Permanente Medical Group, Downey, California 90027, United States; Recruiting
Robert Cooper, Phone: 323-783-5307

Stanford Cancer Center, Stanford, California 94305-5824, United States; Recruiting
Clinical Trials Office - Stanford Cancer Center, Phone: 650-498-7061, Email: cctoffice@stanford.edu

UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California 94115, United States; Recruiting
Clinical Trials Office - UCSF Helen Diller Family Comprehensi, Phone: 877-827-3222

Children's Hospital Center for Cancer and Blood Disorders, Aurora, Colorado 80045, United States; Recruiting
Kelly Maloney, Phone: 720-777-6673

Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center, Farmington, Connecticut 06360-2875, United States; Recruiting
Clinical Trials Office - Carole and Ray Neag Comprehensive Can, Phone: 800-579-7822

All Children's Hospital, St. Petersburg, Florida 33701, United States; Recruiting
Gregory Hale, Phone: 727-767-4176

Kaplan Cancer Center at St. Mary's Medical Center, West Palm Beach, Florida 33407, United States; Recruiting
Narayana Gowda, Phone: 561-844-6363

Lee Cancer Care of Lee Memorial Health System, Fort Myers, Florida 33901, United States; Recruiting
Clinical Trials Office - Lee Cancer Care of Lee Memorial Healt, Phone: 877-680-0008

Memorial Cancer Institute at Memorial Regional Hospital, Hollywood, Florida 33021, United States; Recruiting
Clinical Trials Office - Memorial Cancer Institute, Phone: 954-985-3443

Miami Children's Hospital, Miami, Florida 33155, United States; Recruiting
Enrique Escalon, Phone: 305-662-8360x4960

St. Joseph's Cancer Institute at St. Joseph's Hospital, Tampa, Florida 33607, United States; Recruiting
Clinical Trials Office - St. Joseph's Cancer Institute, Phone: 800-882-4123

Winship Cancer Institute of Emory University, Atlanta, Georgia 30322, United States; Recruiting
Howard M. Katzenstein, Phone: 404-785-0853

Children's Memorial Hospital - Chicago, Chicago, Illinois 60614, United States; Recruiting
Stewart Goldman, Phone: 773-880-3270

Simmons Cooper Cancer Institute, Springfield, Illinois 62794-9677, United States; Recruiting
Clinical Trials Office - Simmons Cooper Cancer Institute, Phone: 217-545-7929

Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana 46202-5289, United States; Recruiting
Clinical Trials Office - Indiana University Cancer Center, Phone: 317-274-2552

Kosair Children's Hospital, Louisville, Kentucky 40232, United States; Recruiting
Clinical Trials Office - Kosair Children's Hospital, Phone: 502-629-5500, Email: CancerResource@nortonhealthcare.org

Lucille P. Markey Cancer Center at University of Kentucky, Lexington, Kentucky 40536-0093, United States; Recruiting
Clinical Trials Office - Markey Cancer Center at University of, Phone: 859-257-3379

Tulane Cancer Center Office of Clinical Research, Alexandria, Louisiana 71315-3198, United States; Recruiting
Clinical Trials Office - Tulane Cancer Center, Phone: 504-988-6121

Alvin and Lois Lapidus Cancer Institute at Sinai Hospital, Baltimore, Maryland 21215, United States; Recruiting
Joseph Wiley, Phone: 410-601-5864

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231-2410, United States; Recruiting
Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Ce, Phone: 410-955-8804, Email: jhcccro@jhmi.edu

Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201-1379, United States; Recruiting
Clinical Trials Office - Barbara Ann Karmanos Cancer Institute, Phone: 313-576-9363

Butterworth Hospital at Spectrum Health, Grand Rapids, Michigan 49503-2560, United States; Recruiting
David S. Dickens, Phone: 616-391-2086

C.S. Mott Children's Hospital at University of Michigan Medical Center, Ann Arbor, Michigan 48109-0286, United States; Recruiting
Clinical Trials Office - C.S. Mott Children's Hospital, Phone: 800-865-1125

Mayo Clinic Cancer Center, Rochester, Minnesota 55905, United States; Recruiting
Clinical Trials Office - All Mayo Clinic Locations, Phone: 507-538-7623

University of Mississippi Cancer Clinic, Jackson, Mississippi 39216-4505, United States; Recruiting
Gail C. Megason, Phone: 601-984-5220

Children's Mercy Hospital, Kansas City, Missouri 64108, United States; Recruiting
Maxine Hetherington, Phone: 816-234-3265

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis, St. Louis, Missouri 63110, United States; Recruiting
Robert J. Hayashi, Phone: 314-454-4118

Children's Hospital, Omaha, Nebraska 68114-4113, United States; Recruiting
Minnie Abromowitch, Phone: 402-955-3950

CCOP - Nevada Cancer Research Foundation, Las Vegas, Nevada 89109-2306, United States; Recruiting
Jonathan Bernstein, Phone: 702-732-0971

Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903, United States; Recruiting
Clinical Trials Office - Cancer Institute of New Jersey, Phone: 732-235-8675

Hackensack University Medical Center Cancer Center, Hackensack, New Jersey 07601, United States; Recruiting
Clinical Trials Office - Hackensack University Medical Center, Phone: 201-996-2879

Overlook Hospital, Morristown, New Jersey 07962, United States; Recruiting
Hazem Mahmoud, Phone: 973-971-6720

University of New Mexico Cancer Center, Albuquerque, New Mexico 87131-5636, United States; Recruiting
Clinical Trials Office - University of New Mexico Cancer Cente, Phone: 505-272-6972

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center, New York, New York 10032, United States; Recruiting
Clinical Trials Office - Herbert Irving Comprehensive Cancer C, Phone: 212-305-8615

James P. Wilmot Cancer Center at University of Rochester Medical Center, Rochester, New York 14642, United States; Recruiting
Barbara L. Asselin, Phone: 585-275-2981

SUNY Upstate Medical University Hospital, Syracuse, New York 13210, United States; Recruiting
Clinical Trials Office - SUNY Upstate Medical University Hospi, Phone: 315-464-5476

Blumenthal Cancer Center at Carolinas Medical Center, Charlotte, North Carolina 28232-2861, United States; Recruiting
Clinical Trials Office - Blumenthal Cancer Center at Carolinas, Phone: 704-355-2884

CCOP - MeritCare Hospital, Fargo, North Dakota 58122, United States; Recruiting
Nathan Kobrinsky, Phone: 701-234-7544

IWK Health Centre, Halifax, Nova Scotia B3K 6R8, Canada; Recruiting
Margaret C. Yhap, Phone: 902-470-8778

Children's Medical Center - Dayton, Dayton, Ohio 45404-1815, United States; Recruiting
Emmett Broxson, Phone: 937-641-3111

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, United States; Recruiting
Clinical Trials Office - Cincinnati Children's Hospital Medica, Phone: 513-636-2799

Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio 44195, United States; Recruiting
Clinical Trials Office - Cleveland Clinic Taussig Cancer Cente, Phone: 866-223-8100

Medical University of Ohio Cancer Center, Toledo, Ohio 43614, United States; Recruiting
Clinical Trials Office - Medical University of Ohio Cancer Cen, Phone: 419-383-6583

Nationwide Children's Hospital, Columbus, Ohio 43205-2696, United States; Recruiting
Amanda Termuhlen, Phone: 614-722-3552

Rainbow Babies and Children's Hospital, Cleveland, Ohio 44106-5000, United States; Recruiting
Yousif (Joe) H. Matloub, Phone: 216-844-3345

Oklahoma University Cancer Institute, Oklahoma City, Oklahoma 73104, United States; Recruiting
Rene Y. McNall-Knapp, Phone: 405-271-5311

Children's Hospital of Eastern Ontario, Ottawa, Ontario K1H 8L1, Canada; Recruiting
Jacqueline Halton, Phone: 613-737-7600x2370

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104-9786, United States; Recruiting
Richard Aplenc, Phone: 267-426-7252

Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States; Recruiting
Clinical Trials Office - Children's Hospital of Pittsburgh, Phone: 412-692-5573

Penn State Cancer Institute at Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033-0850, United States; Recruiting
Clinical Trials Office - Penn State Cancer Institute at Milton, Phone: 717-531-3779, Email: CTO@hmc.psu.edu

St. Christopher's Hospital for Children, Philadelphia, Pennsylvania 19134-1095, United States; Recruiting
Clinical Trials Office - St. Christopher's Hospital for Childr, Phone: 215-427-8991

Hopital Sainte Justine, Montreal, Quebec H3T 1C5, Canada; Recruiting
Yvan Samson, Phone: 418-656-4141x47191

Saskatoon Cancer Centre at the University of Saskatchewan, Saskatoon, Saskatchewan S7N 4H4, Canada; Recruiting
Kaiser Ali, Phone: 306-655-2744

Greenville Hospital Cancer Center, Greenville, South Carolina 29605, United States; Recruiting
Clinical Trials Office - Greenville Hospital Cancer Center, Phone: 864-241-6251

Palmetto Health South Carolina Cancer Center, Columbia, South Carolina 29203, United States; Recruiting
Clinical Trials Office - Palmetto Health South Carolina Cancer, Phone: 803-434-3680

East Tennessee Children's Hospital, Knoxville, Tennessee 37901, United States; Recruiting
Ray C. Pais, Phone: 865-541-8266

St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States; Recruiting
Clinical Trials Office - St. Jude Children's Research Hospital, Phone: 901-595-4644

Baylor University Medical Center - Houston, Houston, Texas 77030-2399, United States; Recruiting
Patrick A. Thompson, Phone: 832-824-4029

Cook Children's Medical Center - Fort Worth, Fort Worth, Texas 76104, United States; Recruiting
Clinical Trials Office - Cook's Children's Medical Center, Phone: 682-885-2103

Driscoll Children's Hospital, Corpus Christi, Texas 78411, United States; Recruiting
Clinical Trials Office - Driscoll Children's Hospital, Phone: 361-694-5311

Methodist Children's Hospital of South Texas, San Antonio, Texas 78229-3993, United States; Recruiting
Michael S. Grimley, Phone: 210-575-7268

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas, Texas 75390, United States; Recruiting
Clinical Trials Office - Simmons Comprehensive Cancer Center a, Phone: 866-460-4673; 214-648-7097

Primary Children's Medical Center, Salt Lake City, Utah 84113-1100, United States; Recruiting
Phillip E. Barnette, Phone: 801-662-4700

Children's Hospital of The King's Daughters, Norfolk, Virginia 23507-1971, United States; Recruiting
Eric J. Lowe, Phone: 757-668-7243

Inova Fairfax Hospital, Falls Church, Virginia 22042-3300, United States; Recruiting
Clinical Trials Office - Inova Fairfax Hospital, Phone: 703-208-6650

Providence Cancer Center at Sacred Heart Medical Center, Spokane, Washington 99220-2555, United States; Recruiting
Judy L. Felgenhauer, Phone: 509-474-2777

West Virginia University Health Sciences Center - Charleston, Charleston, West Virginia 25302, United States; Recruiting
Allen R. Chauvenet, Phone: 304-388-1552

Princess Margaret Hospital for Children, Perth, Western Australia 6001, Australia; Recruiting
Catherine Cole, Phone: 011-6189340-8238

Midwest Children's Cancer Center at Children's Hospital of Wisconsin, Milwaukee, Wisconsin 53226, United States; Recruiting
Michael E. Kelly, Phone: 414-456-4170

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: February 2006
Last updated: October 17, 2009