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

Basic Trial Information

Trial Description

Summary

This clinical trial is studying the side effects and how well giving temozolomide and cixutumumab together with combination chemotherapy works in treating patients with metastatic rhabdomyosarcoma. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving temozolomide and cixutumumab together with combination chemotherapy may kill more tumor cells.

Further Study Information

PRIMARY OBJECTIVES:

I. To determine the feasibility of administering cixutumumab in combination with an intensive multi-agent interval compressed chemotherapy regimen for the treatment of high-risk metastatic rhabdomyosarcoma (RMS).

II. To determine the feasibility of adding temozolomide to vincristine and irinotecan in these patients.

III. To assess immediate and short-term side effects of concurrent temozolomide, vincristine, and irinotecan with radiotherapy in these patients.

SECONDARY OBJECTIVES:

I. To gain a preliminary estimate of the response rate to cixutumumab or temozolomide, vincristine, and irinotecan in these patients.

II. To obtain preliminary efficacy data for cixutumumab or temozolomide in combination with an intensive multi-agent interval compressed chemotherapy regimen in these patients.

III. To determine the effectiveness of detecting metastatic disease with fludeoxyglucose F 18 positron emission tomography (FDG PET) and to compare assessment of response using standard imaging techniques with response assessed by FDG PET.

IV. To assess changes in serum levels of IGF-I, IGF-II, IGF-BP3 as biomarkers of IGF-IR inhibition.

OUTLINE: This is a dose-escalation study of cixutumumab. Patients are assigned to 1 of 2 treatment groups according to the timing of their enrollment onto the study.

GROUP 1: Patients receive vincristine sulfate IV on day 1 of weeks 1-5, 7, 8, 11, 12, 15, 16, 20-24, 28, 29, 32, 33, 35, 38, 41-44, 47, 48, 50, and 51; irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 1, 4, 20, 23, 47, and 50; ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 of weeks 9, 13, 17, 26, and 30; doxorubicin hydrochloride IV on days 1 and 2 of weeks 7, 11, 15, 28, and 32; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 7, 11, 15, 28, 32, 35, 38, 41, and 44; dactinomycin IV on day 1 of weeks 35, 38, 41, and 44; and cixutumumab IV over 1 hour on day 1 of weeks 1-51. Patients also undergo radiotherapy* on days 1-5 of weeks 20-24.

GROUP 2: Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, and dactinomycin and undergo radiotherapy* as in group 1. Patients also receive oral temozolomide on days 1-5 of weeks 1, 4, 20, 23, 47, and 50.

GROUP 3: Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, dactinomycin, and cixutumumab and undergo radiotherapy* as in group 1. Patients also receive temozolomide as in group 2. (Discontinued as of January 2013)

NOTE: *Patients with parameningeal tumors and evidence of intracranial extension or those requiring emergency radiotherapy may receive radiotherapy starting in week 1; cixutumumab should be withheld during radiotherapy.

After completion of study therapy, patients are followed up periodically for up to 10 years.

Eligibility Criteria

Inclusion Criteria:

• Newly diagnosed, biopsy-confirmed metastatic rhabdomyosarcoma (RMS) or ectomesenchymoma

• Stage IV, Clinical Group IV

• RMS with parameningeal and paraspinal primary tumors, including those with intracranial extension by contrast magnetic resonance imaging (MRI) showing that the primary tumor touches, displaces, invades, distorts, or otherwise causes signal abnormality of the dura in brain or spinal cord in contiguity to the primary site, are allowed; ICE is also presumed to exist if the cerebrospinal fluid (CSF) cytopathology is positive for tumor at diagnosis

• Has undergone initial surgery (including biopsy) that provided the definitive diagnosis within the past 42 days

• Enrollment on COG-D9902 required

• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age

• Absolute neutrophil count (ANC) >= 750/μL

• Abnormal blood counts are permissible if there is bone marrow biopsy or aspirate proven bone marrow involvement by RMS

• Platelet count >= 75,000/μL

• Abnormal blood counts are permissible if there is bone marrow biopsy or aspirate proven bone marrow involvement by RMS

• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min OR maximum serum creatinine based on age/gender as follows:

• 0.4 mg/dL (for patients 1 to 5 months of age)

• 0.5 mg/dL (for patients 6 to 11 months of age)

• 0.6 mg/dL (for patients 1 year of age)

• 0.8 mg/dL (for patients 2 to 5 years of age)

• 1.0 mg/dL (for patients 6 to 9 years of age)

• 1.2 mg/dL (for patients 10 to 12 years of age)

• 1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age)

• 1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients >= 16 years of age)

• Patients with urinary tract obstruction by tumor must meet the renal function criteria listed above AND must have unimpeded urinary flow established via decompression of the obstructed portion of the urinary tract

• Total bilirubin =< 1.5 times upper limit of normal (ULN) for age (unless there is evidence of biliary obstruction by the tumor)

• Shortening fraction >=≥ 27% by echocardiogram (ECHO) OR ejection fraction >= 50% by radionuclide angiogram

• Not pregnant or nursing

• Negative pregnancy test

• Sexually active patients of childbearing potential must agree to use effective contraception during therapy (groups1 and 2) and for at least 3 months after the last dose of cixutumumab (group 1)

• No uncontrolled infection

• No known type I or type II diabetes mellitus (for patients enrolled in group 1)

• No prior chemotherapy or radiotherapy except corticosteroids or emergent radiotherapy

• Patients requiring emergency radiation are eligible

• No concurrent growth hormone therapy

• All patients and/or their parents or legal guardians must sign a written informed consent

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Suman Malempati

Principal Investigator

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
	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
	Jonsson Comprehensive Cancer Center at UCLA
		Pamela H Kempert	Ph: 310-825-6708
	Mattel Children's Hospital at UCLA
		Pamela H Kempert	Ph: 310-825-6708
	Madera
	Children's Hospital Central California
		Vonda L Crouse	Ph: 866-353-5437
	Oakland
	Children's Hospital and Research Center Oakland
		Joseph C Torkildson	Ph: 510-450-7600
	Kaiser Permanente-Oakland
		Steven K Bergstrom	Ph: 626-564-3455
	Orange
	Children's Hospital of Orange County
		Violet Shen	Ph: 714-997-3000
	Palo Alto
	Lucile Packard Children's Hospital at Stanford University Medical Center
		Neyssa M Marina	Ph: 650-498-7061
			Email: clinicaltrials@med.stanford.edu
	San Diego
	Rady Children's Hospital - San Diego
		William D Roberts	Ph: 858-966-5934
	San Francisco
	UCSF Helen Diller Family Comprehensive Cancer Center
		Robert E Goldsby	Ph: 877-827-3222
Colorado
	Aurora
	Children's Hospital Colorado Center for Cancer and Blood Disorders
		Edythe A Albano	Ph: 720-777-6672
	Denver
	Presbyterian - St. Luke's Medical Center
		Jennifer J Clark	Ph: 866-775-6246
Connecticut
	Hartford
	Connecticut Children's Medical Center
		Michael S Isakoff	Ph: 860-545-9981
	New Haven
	Yale Cancer Center
		Nina S Kadan-Lottick	Ph: 203-785-5702
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
	Hollywood
	Joe DiMaggio Children's Hospital
		Iftikhar Hanif	Ph: 954-265-2234
	Jacksonville
	Nemours Children's Clinic
		Eric S Sandler	Ph: 904-697-3529
	Orlando
	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
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
		David O Walterhouse	Ph: 773-880-4562
	University of Chicago Cancer Research Center
		Susan L Cohn	Ph: 773-834-7424
	Maywood
	Cardinal Bernardin Cancer Center at Loyola University Medical Center
		Ricarchito B Manera	Ph: 708-226-4357
	Peoria
	Saint Jude Midwest Affiliate
		Pedro A De Alarcon	Ph: 309-655-3258
	Springfield
	Simmons Cooper Cancer Institute
		Gregory P Brandt	Ph: 217-545-7929
Indiana
	Indianapolis
	Riley's Children Cancer Center at Riley Hospital for Children
		Robert J Fallon	Ph: 317-274-2552
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
Maryland
	Baltimore
	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
		Joseph M Wiley	Ph: 410-601-6120
			Email: pridgely@lifebridgehealth.org
	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
		David M Loeb	Ph: 410-955-8804
			Email: jhcccro@jhmi.edu
	Bethesda
	National Naval Medical Center
		Anne B Warwick	Ph: 301-319-2100
Massachusetts
	Boston
	Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
		Carlos Rodriguez-Galindo	Ph: 866-790-4500
Michigan
	Detroit
	Wayne State University
		Maxim Y Yankelevich	Ph: 313-576-9363
	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
Minnesota
	Minneapolis
	Children's Hospitals and Clinics of Minnesota - Minneapolis
		Bruce C Bostrom	Ph: 612-813-5193
	Masonic Cancer Center at University of Minnesota
		Brenda J Weigel	Ph: 612-624-2620
	Rochester
	Mayo Clinic Cancer Center
		Carola A. S. Arndt	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
	Cardinal Glennon Children's Hospital
		William S Ferguson	Ph: 314-268-4000
	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
		Frederick S Huang	Ph: 409-772-1950
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
	New Brunswick
	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
		Richard A Drachtman	Ph: 732-235-8675
	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
	Albany
	Albany Medical Center Hospital
		Vikramjit S Kanwar	Ph: 518-262-3368
	New York
	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
		Alice Lee	Ph: 212-305-8615
	New York University Medical Center
		Linda Granowetter	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
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
	Durham
	Duke Cancer Institute
		Susan G Kreissman	Ph: 888-275-3853
	Winston-Salem
	Wake Forest University Comprehensive Cancer Center
		Thomas W McLean	Ph: 336-713-6771
Ohio
	Akron
	Akron Children's Hospital
		Steven J Kuerbitz	Ph: 330-543-3193
	Cincinnati
	Cincinnati Children's Hospital Medical Center
		John P Perentesis	Ph: 513-636-2799
	Cleveland
	Cleveland Clinic Taussig Cancer Center
		Margaret C Thompson	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
Oklahoma
	Oklahoma City
	Oklahoma University Cancer Institute
		Rene Y McNall-Knapp	Ph: 405-271-4272
			Email: julie-traylor@ouhsc.edu
	Tulsa
	Natalie Warren Bryant Cancer Center at St. Francis Hospital
		Gregory B Kirkpatrick	Ph: 918-494-2200
Oregon
	Portland
	Knight Cancer Institute at Oregon Health and Science University
		Suman Malempati	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
	Bethlehem
	Lehigh Valley Hospital - Muhlenberg
		Philip M Monteleone	Ph: 484-884-2201
	Hershey
	Penn State Children's Hospital
		Lisa M McGregor	Ph: 717-531-6012
	Philadelphia
	Children's Hospital of Philadelphia
		Frank M Balis	Ph: 215-590-2810
	Pittsburgh
	Children's Hospital of Pittsburgh of UPMC
		Scott H Maurer	Ph: 412-692-5573
Rhode Island
	Providence
	Rhode Island Hospital Comprehensive Cancer Center
		Cindy L Schwartz	Ph: 401-444-1488
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
		Cary E Stroud	Ph: 864-241-6251
	Cancer Centers of the Carolinas - Faris Road
		Cary E Stroud	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
	Memphis
	St. Jude Children's Research Hospital
		Wayne L Furman	Ph: 901-595-4644
	Nashville
	Vanderbilt-Ingram Cancer Center
		Scott C Borinstein	Ph: 800-811-8480
Texas
	Corpus Christi
	Driscoll Children's Hospital
		M. C Johnson	Ph: 361-694-5311
	Dallas
	Medical City Dallas Hospital
		Carl Lenarsky	Ph: 972-566-5588
	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
		Naomi J Winick	Ph: 214-648-7097
	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
Utah
	Salt Lake City
	Primary Children's Medical Center
		Phillip E Barnette	Ph: 801-585-5270
Virginia
	Norfolk
	Children's Hospital of The King's Daughters
		Eric J Lowe	Ph: 757-668-7243
	Richmond
	Virginia Commonwealth University Massey Cancer Center
		Madhu S Gowda	Ph: 804-628-1939
Washington
	Seattle
	Children's Hospital and Regional Medical Center - Seattle
		Douglas S Hawkins	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
West Virginia
	Charleston
	West Virginia University Medical School - Charleston
		Allen R Chauvenet	Ph: 304-388-9944
Wisconsin
	Green Bay
	St. Vincent Hospital Regional Cancer Center
		John R Hill	Ph: 920-433-8889
	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
Queensland
	Herston
	Royal Brisbane and Women's Hospital
		Helen Irving	Ph: 888-823-5923
			Email: ctsucontact@westat.com
	Royal Children's Hospital
		Helen Irving	Ph: 888-823-5923
			Email: ctsucontact@westat.com
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
British Columbia
	Vancouver
	Children's and Women's Hospital of British Columbia
		Caron Strahlendorf	Ph: 604-875-2345ext6477
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
	Toronto
	Hospital for Sick Children
		David Malkin	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
New Zealand
Auckland
	Grafton
	Starship Children's Health
		Mark A Winstanley	Ph:  0800 728 436

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01055314
Information obtained from ClinicalTrials.gov on April 01, 2013

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