Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with a peripheral stem cell transplant may allow more chemotherapy to be given so that more tumor cells are killed. It is not yet known which combination chemotherapy regimen is more effective when given before a peripheral stem cell transplant in treating supratentorial primitive neuroectodermal tumors or medulloblastoma.

PURPOSE: This randomized phase III trial is studying two different combination chemotherapy regimens to compare how well they work when given before a peripheral stem cell transplant in treating young patients with newly diagnosed supratentorial primitive neuroectodermal tumors or high-risk medulloblastoma .

Further Study Information

OBJECTIVES:

Primary

• Determine if treatment of pediatric patients with newly diagnosed supratentorial primitive neuroectodermal CNS tumors or high-risk medulloblastoma with intensive induction chemotherapy comprising vincristine, etoposide, cyclophosphamide, and cisplatin in combination with high-dose methotrexate and leucovorin calcium followed by consolidation chemotherapy comprising carboplatin and thiotepa and peripheral blood stem cell rescue results in a higher complete response rate then in patients treated with the same regimen without high-dose methotrexate and leucovorin calcium.

Secondary

• Determine whether biologic characterization of these tumors will refine therapeutic stratification separating atypical teratoid rhabdoid tumors from primitive neuroectodermal tumors (PNETs) and possibly identifying other markers of value for stratification within the group of PNETs.

• Compare event-free survival and patterns of failure in patients treated with these regimens.

• Compare the acute, chronic, and late effects of these regimens, particularly in terms of tolerance to the same consolidation regimen after treatment with 2 different induction regimens, in these patients.

• Compare the gastrointestinal and nutritional toxicities of these regimens in these patients.

• Compare the quality of life outcomes in patients treated with these regimens.

• Compare the neuropsychological effects of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to diagnosis* (M0 medulloblastoma with ≥ 1.5 cm² residual tumor vs M1 medulloblastoma [positive lumbar CSF cytology] vs M2, M3, or M4 medulloblastoma vs supratentorial PNET [any M-stage] vs M0 medulloblastoma < 8 months without residual disease or with < 1.5 cm² radiographic measurable residual tumor vs anaplastic M0 medulloblastoma without residual disease or with < 1.5 cm² radiographic measurable residual vs classic M0 (nondesmoplastic) medulloblastoma with < 1.5 cm² radiographic measurable residual tumor).NOTE: *All diagnoses are for children < 36 months unless otherwise noted.

• Induction therapy: Patients are randomized to 1 of 2 induction treatment arms.

• Arm I: Patients receive vincristine IV on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3; and filgrastim (G-CSF) IV or subcutaneously (SC) beginning on day 4 and continuing until blood counts recover. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.

• Arm II : Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Once methotrexate levels are in a safe range, patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Patients also receive G-CSF IV or SC beginning 24 hours after the completion of chemotherapy and continuing until blood counts recover. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.

In both arms, patients with stable disease or partial response after induction therapy proceed to second-look surgery followed by consolidation therapy. Patients with a complete response after induction therapy proceed directly to consolidation therapy.

• Consolidation therapy: Beginning no more than 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and G-CSF IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous peripheral blood stem cells IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.

Blood and tissue samples are collected at baseline for correlative studies, including gene expression profiling, biological marker analysis (i.e., cMyc, ErbB2/ErbB4), comparative genome analysis, and mutation analysis.

After completion of study therapy, patients are followed periodically.

PROJECTED ACCRUAL: A total of 96 patients will be accrued for this study.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:

• High-risk medulloblastoma defined by any of the following:

• Residual disease > 1.5 cm²

• Lumbar cerebral spinal fluid cytology positive for tumor cells by analysis of fluid collected either before definitive surgery or ≥ 10 days after definitive surgery unless contraindicated

• M0 disease in children < 8 months of age at diagnosis

• M2 or M3 metastatic disease by MRI

• M4 disease

• Supratentorial primitive neuroectodermal tumor (PNET) (any M-stage)

• Anaplastic medulloblastoma regardless of M-stage or residual tumor

• M0 classic, non-desmoplastic medulloblastoma (R1) with radiographically measurable residual disease < 1.5 cm^2

• MRI evidence of spinal disease

• Tumor must be negative for INI1 gene

• Has undergone definitive surgery within the past 31 days

• No atypical teratoid rhabdoid tumors

• Biological specimens must be available for correlative laboratory studies

PATIENT CHARACTERISTICS:

• Life expectancy > 8 weeks

• Creatinine clearance or radioisotope glomerular filtration rate ≥ 60 mL/min

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

• AST and ALT < 2 times ULN

• Shortening fraction ≥ 27% by echocardiogram

• Ejection fraction ≥ 47% by radionuclide angiogram

• No evidence of dyspnea at rest

• Pulse oximetry > 94% on room air

• Absolute neutrophil count > 1,000/mm³

• Platelet count > 100,000/mm³ (transfusion independent)

• Hemoglobin > 8 g/dL (RBC transfusions allowed)

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior radiation therapy or chemotherapy

• Prior corticosteroids allowed

Trial Contact Information

Trial Lead Organizations/Sponsors

Children's Oncology Group

Claire Mazewski

Study Chair

Stewart John Kellie

U.S.A.
Alabama
	Birmingham
	Children's Hospital of Alabama at University of Alabama at Birmingham
		Alyssa T Reddy	Ph: 205-934-0309
	UAB Comprehensive Cancer Center
		Alyssa T Reddy	Ph: 205-934-0309
Arizona
	Phoenix
	Phoenix Children's Hospital
		Jessica Boklan	Ph: 602-546-0920
Arkansas
	Little Rock
	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
		David L Becton	Ph: 501-364-7373
California
	Downey
	Southern California Permanente Medical Group
		Robert M Cooper	Ph: 626-564-3455
	Loma Linda
	Loma Linda University Cancer Institute at Loma Linda University Medical Center
		Antranik A Bedros	Ph: 909-558-3375
	Long Beach
	Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
		Amanda M Termuhlen	Ph: 562-933-5437
	Los Angeles
	Childrens Hospital Los Angeles
		Leo Mascarenhas	Ph: 323-361-4110
	Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
		Fataneh (Fae) Majlessipour	Ph: 310-423-8965
	Madera
	Children's Hospital Central California
		Vonda L Crouse	Ph: 866-353-5437
	Orange
	Children's Hospital of Orange County
		Violet Shen	Ph: 714-997-3000
	Sacramento
	University of California Davis Cancer Center
		Jay Michael S Balagtas	Ph: 916-734-3089
	San Diego
	Rady Children's Hospital - San Diego
		William D Roberts	Ph: 858-966-5934
	San Francisco
	UCSF Helen Diller Family Comprehensive Cancer Center
		Anuradha Banerjee	Ph: 877-827-3222
Colorado
	Aurora
	Children's Hospital Colorado Center for Cancer and Blood Disorders
		Nicholas K Foreman	Ph: 720-777-6672
Connecticut
	Hartford
	Connecticut Children's Medical Center
		Michael S Isakoff	Ph: 860-545-9981
Delaware
	Wilmington
	Alfred I. duPont Hospital for Children
		Christopher N Frantz	Ph: 302-651-5755
District of Columbia
	Washington
	Children's National Medical Center
		Jeffrey S Dome	Ph: 202-884-2549
Florida
	Fort Lauderdale
	Broward General Medical Center Cancer Center
		Hector M Rodriguez-Cortes	Ph: 954-355-5346
	Fort Myers
	Lee Cancer Care of Lee Memorial Health System
		Emad K Salman	Ph: 239-343-5333
	Gainesville
	University of Florida Shands Cancer Center
		William B Slayton	Ph: 352-273-8675
			Email: trials@cancer.ufl.edu
	Hollywood
	Joe DiMaggio Children's Hospital
		Iftikhar Hanif	Ph: 954-265-2234
	Jacksonville
	Nemours Children's Clinic
		Eric S Sandler	Ph: 904-697-3529
	Miami
	Miami Children's Hospital
		Enrique A Escalon	Ph: 305-662-8360
	Orlando
	Florida Hospital Cancer Institute at Florida Hospital Orlando
		Clifford A Selsky	Ph: 407-303-5623
	M.D. Anderson Cancer Center at Orlando
		Vincent F Giusti	Ph: 321-841-7246
	Nemours Children's Clinic - Orlando
		Ramamoorthy Nagasubramanian	Ph: 407-650-7150
	Pensacola
	Nemours Children's Clinic - Pensacola
		Jeffrey H Schwartz	Ph: 904-697-3529
	Saint Petersburg
	All Children's Hospital
		Gregory A Hale	Ph: 727-767-2423
			Email: HamblinF@allkids.org
	Tampa
	St. Joseph's Children's Hospital of Tampa
		Hardeo K Panchoosingh	Ph: 800-882-4123
	West Palm Beach
	Kaplan Cancer Center at St. Mary's Medical Center
		Narayana Gowda	Ph: 888-823-5923
			Email: ctsucontact@westat.com
Georgia
	Atlanta
	AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
		Howard M Katzenstein	Ph: 888-785-1112
	Savannah
	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
		J. Martin Johnston	Ph: 912-350-8568
Hawaii
	Honolulu
	Cancer Research Center of Hawaii
		Robert W Wilkinson	Ph: 808-983-6090
Idaho
	Boise
	Mountain States Tumor Institute at St. Luke's Regional Medical Center
		Eugenia Chang	Ph: 800-845-4624
Illinois
	Chicago
	Ann and Robert H. Lurie Children's Hospital of Chicago
		Stewart Goldman	Ph: 773-880-4562
	Maywood
	Cardinal Bernardin Cancer Center at Loyola University Medical Center
		Ricarchito B Manera	Ph: 708-226-4357
Indiana
	Indianapolis
	St. Vincent Indianapolis Hospital
		Bassem I Razzouk	Ph: 317-338-2194
Iowa
	Iowa City
	Holden Comprehensive Cancer Center at University of Iowa
		Ayman A El-Sheikh	Ph: 800-237-1225
Kentucky
	Lexington
	University of Kentucky Chandler Medical Center
		Martha F Greenwood	Ph: 859-257-3379
	Louisville
	Kosair Children's Hospital
		Salvatore J Bertolone	Ph: 866-530-5516
Louisiana
	New Orleans
	Tulane Cancer Center at Tulane University Hospital and Clinic
		Tammuella C Singleton	Ph: 504-988-6121
Maine
	Bangor
	CancerCare of Maine at Eastern Maine Medical Center
		Judith B Allen	Ph: 207-973-4274
Maryland
	Baltimore
	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
		Kenneth J Cohen	Ph: 410-955-8804
			Email: jhcccro@jhmi.edu
	Bethesda
	National Naval Medical Center
		Stephen S Roberts	Ph: 212-639-7202
Massachusetts
	Boston
	Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
		Carlos Rodriguez-Galindo	Ph: 866-790-4500
	Floating Hospital for Children at Tufts - New England Medical Center
		Johannes E Wolff	Ph: 617-636-5000
			Email: ContactUsCancerCenter@TuftsMedicalCenter.org
Michigan
	Grand Rapids
	Helen DeVos Children's Hospital at Spectrum Health
		David S Dickens	Ph: 616-267-1925
	Kalamazoo
	Bronson Methodist Hospital
		Jeffrey S Lobel	Ph: 800-227-2345
	Western Michigan University School of Medicine Clinics
		Jeffrey S Lobel	Ph: 800-227-2345
	Lansing
	Breslin Cancer Center at Ingham Regional Medical Center
		Renuka Gera	Ph: 517-334-2765
Minnesota
	Minneapolis
	Children's Hospitals and Clinics of Minnesota - Minneapolis
		Bruce C Bostrom	Ph: 612-813-5193
	Masonic Cancer Center at University of Minnesota
		Christopher L Moertel	Ph: 612-624-2620
	Rochester
	Mayo Clinic Cancer Center
		Amulya A Nageswara Rao	Ph: 507-538-7623
Mississippi
	Jackson
	University of Mississippi Cancer Clinic
		Gail C Megason	Ph: 601-815-6700
Missouri
	Kansas City
	Children's Mercy Hospital
		Maxine L Hetherington	Ph: 816-234-3265
	Saint Louis
	David C. Pratt Cancer Center at St. John's Mercy
		Bethany G. Sleckman	Ph: 913-948-5588
	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
		Shalini Shenoy	Ph: 800-600-3606
			Email: info@siteman.wustl.edu
Nevada
	Las Vegas
	CCOP - Nevada Cancer Research Foundation
		Jonathan Bernstein	Ph: 702-384-0013
New Jersey
	Hackensack
	Hackensack University Medical Center Cancer Center
		Burton E Appel	Ph: 201-996-2879
	Morristown
	Carol G. Simon Cancer Center at Morristown Memorial Hospital
		Steven L Halpern	Ph: 973-971-5900
	Newark
	Newark Beth Israel Medical Center
		Peri Kamalakar	Ph: 973-926-7230
	Paterson
	St. Joseph's Hospital and Medical Center
		Mary A Bonilla	Ph: 973-754-2909
	Summit
	Overlook Hospital
		Steven L Halpern	Ph: 973-971-5900
New Mexico
	Albuquerque
	University of New Mexico Cancer Center
		Koh B Boayue	Ph: 505-272-6972
New York
	Bronx
	Montefiore Medical Center
		Rosanna J Ricafort	Ph: 718-904-2730
			Email: aecc@aecom.yu.edu
	Buffalo
	Roswell Park Cancer Institute
		Martin L Brecher	Ph: 877-275-7724
	Mineola
	Winthrop University Hospital
		Mark E Weinblatt	Ph: 866-946-8476
	New York
	Memorial Sloan-Kettering Cancer Center
		Peter G Steinherz	Ph: 212-639-7202
	New York University Medical Center
		Jeffrey C Allen	Ph: 212-263-4434
			Email: prmc.coordinator@nyumc.org
	Rochester
	James P. Wilmot Cancer Center at University of Rochester Medical Center
		Lisa R Hackney	Ph: 585-275-5830
	Valhalla
	New York Medical College
		Mehmet F Ozkaynak	Ph: 914-594-3794
North Carolina
	Chapel Hill
	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
		Stuart H Gold	Ph: 877-668-0683
	Charlotte
	Blumenthal Cancer Center at Carolinas Medical Center
		Joel A Kaplan	Ph: 704-355-2884
	Presbyterian Cancer Center at Presbyterian Hospital
		Paulette C Bryant	Ph: 704-384-5369
Ohio
	Cincinnati
	Cincinnati Children's Hospital Medical Center
		John P Perentesis	Ph: 513-636-2799
	Cleveland
	Cleveland Clinic Taussig Cancer Center
		Tanya M Tekautz	Ph: 866-223-8100
	Seidman Cancer Center at University Hospitals/Case Medical Center
		Yousif (Joe) H Matloub	Ph: 216-844-5437
	Columbus
	Nationwide Children's Hospital
		Mark A Ranalli	Ph: 614-722-2708
	Dayton
	Dayton Children's - Dayton
		Emmett H Broxson	Ph: 800-228-4055
	Toledo
	Mercy Children's Hospital
		Rama Jasty	Ph: 419-251-8210
	Toledo Hospital
		Dagmar T Stein	Ph: 419-824-1842
Oklahoma
	Oklahoma City
	Oklahoma University Cancer Institute
		Rene Y McNall-Knapp	Ph: 405-271-4272
			Email: julie-traylor@ouhsc.edu
Oregon
	Portland
	Knight Cancer Institute at Oregon Health and Science University
		Kellie J Nazemi	Ph: 503-494-1080
			Email: trials@ohsu.edu
	Legacy Emanuel Children's Hospital
		Janice F Olson	Ph: 503-413-2560
	Legacy Emanuel Hospital and Health Center and Children's Hospital
		Janice F Olson	Ph: 503-413-2560
Pennsylvania
	Danville
	Geisinger Cancer Institute at Geisinger Health
		Jeffrey S Taylor	Ph: 570-271-5251
	Philadelphia
	Children's Hospital of Philadelphia
		Michael J Fisher	Ph: 215-590-2810
	St. Christopher's Hospital for Children
		Gregory E Halligan	Ph: 215-427-8991
	Pittsburgh
	Children's Hospital of Pittsburgh of UPMC
		Arthur K Ritchey	Ph: 412-692-5573
PR
	Santurce
	San Jorge Children's Hospital
		Luis A Clavell	Ph: 888-823-5923
			Email: ctsucontact@westat.com
South Carolina
	Charleston
	Hollings Cancer Center at Medical University of South Carolina
		Jacqueline M Kraveka	Ph: 843-792-9321
	Columbia
	Palmetto Health South Carolina Cancer Center
		Ronnie W. Neuberg	Ph: 803-434-3680
	Greenville
	BI-LO Charities Children's Cancer Center
		Nichole L Bryant	Ph: 864-241-6251
	Cancer Centers of the Carolinas - Faris Road
		Nichole L Bryant	Ph: 864-241-6251
South Dakota
	Sioux Falls
	Sanford Cancer Center at Sanford USD Medical Center
		Kayelyn J Wagner	Ph: 605-328-1367
Tennessee
	Knoxville
	East Tennessee Children's Hospital
		Ray C Pais	Ph: 865-541-8266
	Nashville
	Vanderbilt-Ingram Cancer Center
		Haydar A Frangoul	Ph: 800-811-8480
Texas
	Amarillo
	Texas Tech University Health Sciences Center School of Medicine - Amarillo
		Osvaldo Regueira	Ph: 806-354-5411
	Corpus Christi
	Driscoll Children's Hospital
		M. C Johnson	Ph: 361-694-5311
	Dallas
	Medical City Dallas Hospital
		Carl Lenarsky	Ph: 972-566-5588
	Fort Worth
	Cook Children's Medical Center - Fort Worth
		Mary Meaghan P Granger	Ph: 682-885-2103
	Houston
	Dan L. Duncan Cancer Center at Baylor College of Medicine
		Lisa R Bomgaars	Ph: 713-798-1354
			Email: burton@bcm.edu
	Lubbock
	Covenant Children's Hospital
		Latha Prasannan	Ph: 806-725-8000
			Email: jaccresearch@covhs.org
	San Antonio
	Methodist Children's Hospital of South Texas
		Jaime Estrada	Ph: 210-575-7000
	University of Texas Health Science Center at San Antonio
		Anne-Marie R Langevin	Ph: 210-567-0653
			Email: che@uthscsa.edu
Utah
	Salt Lake City
	Primary Children's Medical Center
		Phillip E Barnette	Ph: 801-585-5270
Vermont
	Burlington
	Vermont Cancer Center at University of Vermont
		Alan C Homans	Ph: 802-656-8990
Virginia
	Richmond
	Virginia Commonwealth University Massey Cancer Center
		Kamar Godder	Ph: 804-628-1939
Washington
	Seattle
	Children's Hospital and Regional Medical Center - Seattle
		Jeffrey R Geyer	Ph: 866-987-2000
	Spokane
	Providence Cancer Center at Sacred Heart Medical Center
		Judy L Felgenhauer	Ph: 800-228-6618
			Email: HopeBeginsHere@providence.org
	Tacoma
	Mary Bridge Children's Hospital and Health Center - Tacoma
		Robert G Irwin	Ph: 888-823-5923
			Email: ctsucontact@westat.com
Wisconsin
	Marshfield
	Marshfield Clinic - Marshfield Center
		Michael J McManus	Ph: 715-389-4457
	Milwaukee
	Midwest Children's Cancer Center at Children's Hospital of Wisconsin
		Michael E Kelly	Ph: 414-805-4380
Australia
New South Wales
	Randwick
	Sydney Children's Hospital
		Draga Barbaric	Ph: (02) 9382-1721
	Sydney
	Children's Hospital at Westmead
		Geoffrey B McCowage	Ph: 61-2-9845 1400
Victoria
	Parkville
	Royal Children's Hospital
		Francoise M Mechinaud
			Email: crdo.info@mcri.edu.au
Western Australia
	Perth
	Princess Margaret Hospital for Children
		Catherine H Cole	Ph: (08) 9340 8330
			Email: admin@childcancerresearch.com.au
Canada
Alberta
	Calgary
	Alberta Children's Hospital
		Douglas R Strother	Ph: 403-220-6898
			Email: research4kids@ucalgary.ca
Manitoba
	Winnipeg
	CancerCare Manitoba
		Rochelle A Yanofsky	Ph: 866-561-1026
			Email: CIO_Web@cancercare.mb.ca
Nova Scotia
	Halifax
	IWK Health Centre
		Margaret C Yhap	Ph: 902-470-8394
Ontario
	Hamilton
	McMaster Children's Hospital at Hamilton Health Sciences
		Carol Portwine	Ph: 905-521-2100ext74595
		Carol Portwine	Ph: 905-521-2100ext74595
	Kingston
	Cancer Centre of Southeastern Ontario at Kingston General Hospital
		Mariana P Silva	Ph: 613-544-2630
	Ottawa
	Children's Hospital of Eastern Ontario
		Jacqueline M Halton	Ph: 613-738-3931
	Toronto
	Hospital for Sick Children
		Ronald M Grant	Ph: 416-813-7654ext2027
			Email: jason.mcguire@sickkids.ca
Quebec
	Montreal
	Hopital Sainte Justine
		Yvan Samson	Ph: 514-345-4931
	Montreal Children's Hospital at McGill University Health Center
		Sharon B Abish	Ph: 514-412-4445
			Email: info@thechildren.com
	Ste-Foy
	Centre de Recherche du Centre Hospitalier de l'Universite Laval
		Bruno Michon	Ph: 418-525-4444

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00336024
Information obtained from ClinicalTrials.gov on November 20, 2012

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