AzTrials
AzTrials

Metastatic Ewing SarcomaPhase 3NCT02306161

Combination Chemotherapy With or Without Ganitumab in Treating Patients With Newly Diagnosed Metastatic Ewing Sarcoma

A Phase 3 study testing Cyclophosphamide, Doxorubicin and Doxorubicin Hydrochloride in people with Metastatic Ewing Sarcoma and Metastatic Malignant Neoplasm in the Bone, run by National Cancer Institute (NCI) at 314 sites in 3 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

This randomized phase III trial studies how well combination chemotherapy with or without ganitumab works in treating patients with newly diagnosed Ewing sarcoma that has spread to other parts of the body. Read more about this study

Who is it for?
Ages Up to 50 years
What is being tested?
Cyclophosphamide, Doxorubicin and Doxorubicin Hydrochloride
Could I receive a placebo?
No, everyone receives an active treatment
How many people
312 participants
Where
314 sitesin 3 countries
Study dates
12 Dec 2014to 16 Sep 2027
Phase
Phase 3

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 50 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Patients with histologic diagnosis (by institutional pathologist) of newly diagnosed Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET) arising from bone or soft tissue and with metastatic disease involving lung, bone, bone marrow, or other metastatic site
  • For the purpose of this study metastatic disease is defined as one or more of the following:
  • Lesions which are discontinuous from the primary tumor, are not regional lymph nodes, and do not share a bone or body cavity with the primary tumor; skip lesions in the same bone as the primary tumor do not constitute metastatic disease; skip lesions in an adjacent bone are considered bone metastases; if there is any doubt whether lesions are metastatic, a biopsy of those lesions should be performed
  • Contralateral pleural effusion and/or contralateral pleural nodules
  • Distant lymph node involvement
  • Patients with pulmonary nodules are considered to have metastatic disease if the patient has:
Show all 30Show fewer
  • Solitary nodule >= 0.5 cm or multiple nodules of >= 0.3 cm unless lesion is biopsied and negative for tumor
  • Patients with solitary nodule < 0.5 cm or multiple nodules < 0.3 cm are not considered to have lung metastasis unless biopsy documents tumor
  • Bone marrow metastatic disease is based on morphologic evidence of Ewing sarcoma based on hematoxylin and eosin (H\&E) stains; in the absence of morphologic evidence of marrow involvement on H\&E, patients with bone marrow involvement detected ONLY by flow cytometry, reverse-transcriptase (RT)-polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), or immunohistochemistry will NOT be considered to have clinical bone marrow involvement for the purposes of this study
  • This study requires bilateral bone marrow biopsies at study entry; the suggested approach for patients with large pelvic tumors in which a posterior iliac crest bone marrow biopsy would track through the tumor is to instead undergo 2 marrow biopsies on the contralateral side (either 2 posterior biopsies or one posterior and one anterior biopsy)
  • Bone metastasis: This study utilizes whole body FDG-PET scans to screen patients for bone metastases; areas suspicious for bone metastasis based on FDG-PET scans require confirmatory anatomic imaging with either MRI or computed tomography (CT) (whole body FDG-PET/CT or FDG-PET/magnetic resonance [MR] scan acceptable); whole body technetium bone scans may be performed at the discretion of the investigator and are not required; for patients without other sites of metastatic disease whose sole metastatic site to qualify for study entry is a single area suspicious for bone metastasis identified by FDG-PET, confirmatory biopsy or anatomic imaging evidence of an associated soft tissue mass at that site is required for study entry
  • Patients must have adequate tumor tissue to meet the minimum requirement for submission
  • Enrolling institutions are reminded that submission of pre-treatment serum, tumor tissue and whole blood is required
  • Patients should only have had a biopsy of the primary tumor without an attempt at complete or partial resection; patients will still be eligible if excision was attempted or accomplished as long as adequate anatomic imaging (MRI for most primary tumor sites) was obtained prior to surgery
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows (performed within 7 days prior to enrollment):
  • Age < 6 months: Maximum serum creatinine (mg/dL): 0.4 for males and females
  • Age 6 months to < 1 year: Maximum serum creatinine (mg/dL): 0.5 for males and females
  • Age 1 to < 2 years: Maximum serum creatinine (mg/dL): 0.6 for males and females
  • Age 2 to < 6 years: Maximum serum creatinine (mg/dL): 0.8 for males and females
  • Age 6 to < 10 years: Maximum serum creatinine (mg/dL): 1 for males and females
  • Age 10 to < 13 years: Maximum serum creatinine (mg/dL): 1.2 for males and females
  • Age 13 to < 16 years: Maximum serum creatinine (mg/dL): 1.5 for males and 1.4 for females
  • Age >= 16 years: Maximum serum creatinine (mg/dL): 1.7 for males and 1.4 for females
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (performed within 7 days prior to enrollment), and
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 3 x upper limit of normal (ULN) for age (performed within 7 days prior to enrollment) (except for patients with liver metastasis who may enroll if ALT < 5 times ULN for age)
  • Shortening fraction of >= 27% or
  • Ejection fraction of >= 50%
  • Patients must have a normal blood sugar level for age to participate; if an initial random draw (ie. non-fasting) blood glucose value is out of range, it is acceptable to repeat this test as a fasting draw
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Who cannot join

  • Patients with regional node involvement as their only site of disease beyond the primary tumor will not be eligible
  • Patients whose primary tumors arise in the intra-dural soft tissue (e.g. brain and spinal cord) are not eligible
  • Patients who have received prior chemotherapy or radiation therapy are not eligible
  • Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained; lactating females are not eligible unless they have agreed not to breastfeed their infants for the duration of protocol therapy; sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of protocol therapy
  • Patients with known pre-existing diabetes mellitus will be excluded from study
  • Patients receiving chronic pharmacologic doses of corticosteroids are not eligible; for the purposes of eligibility, chronic exposure is defined as anticipated exposure of > 3 weeks, including the sum of both pre-enrollment and anticipated post-enrollment dosing; patients on acute corticosteroid therapy (=< 3 weeks of total planned exposure) must still meet the normal blood glucose requirement; patients receiving chronic inhaled corticosteroids or chronic physiologic replacement doses of corticosteroids are eligible

Trial locations and contacts

314 sites in 3 countries.

314 sites in 3 countries

United States298 sites

  • Children's Hospital Medical Center of Akron

    Akron, Ohio, 44308

  • Albany Medical Center

    Albany, New York, 12208

  • Lehigh Valley Hospital-Cedar Crest

    Allentown, Pennsylvania, 18103

  • Providence Alaska Medical Center

    Anchorage, Alaska, 99508

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • University of Michigan Rogel Cancer Center

    Ann Arbor, Michigan, 48109

  • Mission Hospital

    Asheville, North Carolina, 28801

  • Children's Healthcare of Atlanta - Arthur M Blank Hospital

    Atlanta, Georgia, 30329

  • Augusta University Medical Center

    Augusta, Georgia, 30912

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Rush-Copley Medical Center

    Aurora, Illinois, 60504

  • Dell Children's Medical Center of Central Texas

    Austin, Texas, 78723

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Sinai Hospital of Baltimore

    Baltimore, Maryland, 21215

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Eastern Maine Medical Center

    Bangor, Maine, 04401

  • CommonSpirit Saint Joseph Hospital - Bardstown

    Bardstown, Kentucky, 40004

  • Bronson Battle Creek

    Battle Creek, Michigan, 49017

  • Nebraska Medicine-Bellevue

    Bellevue, Nebraska, 68123

  • Central Vermont Medical Center/National Life Cancer Treatment

    Berlin Corners, Vermont, 05602

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889-5600

  • Lehigh Valley Hospital - Muhlenberg

    Bethlehem, Pennsylvania, 18017

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

  • Saint Luke's Cancer Institute - Boise

    Boise, Idaho, 83712

  • Central Care Cancer Center - Bolivar

    Bolivar, Missouri, 65613

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Cox Cancer Center Branson

    Branson, Missouri, 65616

  • Saint Joseph Regional Cancer Center

    Bryan, Texas, 77802

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Saint Anne Hospital

    Burien, Washington, 98166

  • University of Vermont Medical Center

    Burlington, Vermont, 05401

  • University of Vermont and State Agricultural College

    Burlington, Vermont, 05405

  • Carson Tahoe Regional Medical Center

    Carson City, Nevada, 89703

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • T C Thompson Children's Hospital

    Chattanooga, Tennessee, 37403

  • Memorial Hospital

    Chattanooga, Tennessee, 37404

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60611

  • University of Illinois

    Chicago, Illinois, 60612

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Good Samaritan Hospital - Cincinnati

    Cincinnati, Ohio, 45220

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Bethesda North Hospital

    Cincinnati, Ohio, 45242

  • TriHealth Cancer Institute-Westside

    Cincinnati, Ohio, 45247

  • TriHealth Cancer Institute-Anderson

    Cincinnati, Ohio, 45255

  • Rainbow Babies and Childrens Hospital

    Cleveland, Ohio, 44106

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Mercy Cancer Center-West Lakes

    Clive, Iowa, 50325

  • UI Health Care Mission Cancer and Blood - West Des Moines Clinic

    Clive, Iowa, 50325

  • Penrose-Saint Francis Healthcare

    Colorado Springs, Colorado, 80907

  • Rocky Mountain Cancer Centers-Penrose

    Colorado Springs, Colorado, 80907

  • University of Missouri Children's Hospital

    Columbia, Missouri, 65212

  • Prisma Health Richland Hospital

    Columbia, South Carolina, 29203

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • Commonwealth Cancer Center-Corbin

    Corbin, Kentucky, 40701

  • Driscoll Children's Hospital

    Corpus Christi, Texas, 78411

  • Alegent Health Mercy Hospital

    Council Bluffs, Iowa, 51503

  • Greater Regional Medical Center

    Creston, Iowa, 50801

  • Medical City Dallas Hospital

    Dallas, Texas, 75230

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Carle at The Riverfront

    Danville, Illinois, 61832

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

  • Dayton Children's Hospital

    Dayton, Ohio, 45404

  • AdventHealth Porter

    Denver, Colorado, 80210

  • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

    Denver, Colorado, 80218

  • Blank Children's Hospital

    Des Moines, Iowa, 50309

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • UI Health Care Mission Cancer and Blood - Laurel Clinic

    Des Moines, Iowa, 50314

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Henry Ford Health Saint John Hospital

    Detroit, Michigan, 48236

  • Kaiser Permanente Downey Medical Center

    Downey, California, 90242

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Essentia Health Cancer Center

    Duluth, Minnesota, 55805

  • CommonSpirit Cancer Center Mercy

    Durango, Colorado, 81301

  • Mercy Medical Center

    Durango, Colorado, 81301

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

  • El Paso Children's Hospital

    El Paso, Texas, 79905

  • Saint Elizabeth Hospital

    Enumclaw, Washington, 98022

  • Deaconess Clinic Downtown

    Evansville, Indiana, 47713

  • Inova Fairfax Hospital

    Falls Church, Virginia, 22042

  • Sanford Broadway Medical Center

    Fargo, North Dakota, 58122

  • Saint Francis Hospital

    Federal Way, Washington, 98003

  • Hurley Medical Center

    Flint, Michigan, 48503

  • Golisano Children's Hospital of Southwest Florida

    Fort Myers, Florida, 33908

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

  • UF Health Cancer Institute - Gainesville

    Gainesville, Florida, 32610

  • Glens Falls Hospital

    Glens Falls, New York, 12801

  • Mountain Blue Cancer Care Center

    Golden, Colorado, 80401

  • Nebraska Cancer Specialists/Oncology Hematology West PC

    Grand Island, Nebraska, 68803

  • Corewell Health Grand Rapids Hospitals - Butterworth Hospital

    Grand Rapids, Michigan, 49503

  • Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

    Grand Rapids, Michigan, 49503

  • Trinity Health Grand Rapids Hospital

    Grand Rapids, Michigan, 49503

  • Saint Vincent Hospital Cancer Center Green Bay

    Green Bay, Wisconsin, 54301

  • Saint Francis Hospital

    Greenville, South Carolina, 29601

  • BI-LO Charities Children's Cancer Center

    Greenville, South Carolina, 29605

  • Saint Francis Cancer Center

    Greenville, South Carolina, 29607

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Connecticut Children's Medical Center

    Hartford, Connecticut, 06106

  • Comprehensive Cancer Centers of Nevada-Horizon Ridge

    Henderson, Nevada, 89052

  • Penn State Children's Hospital

    Hershey, Pennsylvania, 17033

  • Pulmonary Medicine Center of Chattanooga-Hixson

    Hixson, Tennessee, 37343

  • Memorial Regional Hospital/Joe DiMaggio Children's Hospital

    Hollywood, Florida, 33021

  • Straub Clinic and Hospital

    Honolulu, Hawaii, 96813

  • Kaiser Permanente Moanalua Medical Center

    Honolulu, Hawaii, 96819

  • Kapiolani Medical Center for Women and Children

    Honolulu, Hawaii, 96826

  • CHI Saint Vincent Cancer Center Hot Springs

    Hot Springs, Arkansas, 71913

  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

    Houston, Texas, 77030

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • Ascension Saint Vincent Indianapolis Hospital

    Indianapolis, Indiana, 46260

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Nemours Children's Clinic-Jacksonville

    Jacksonville, Florida, 32207

  • Freeman Health System

    Joplin, Missouri, 64804

  • Mercy Hospital Joplin

    Joplin, Missouri, 64804

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007

  • Beacon Kalamazoo

    Kalamazoo, Michigan, 49048

  • Children's Mercy Hospitals and Clinics

    Kansas City, Missouri, 64108

  • Fred and Pamela Buffett Cancer Center - Kearney

    Kearney, Nebraska, 68845

  • CHI Health Good Samaritan

    Kearney, Nebraska, 68847

  • East Tennessee Childrens Hospital

    Knoxville, Tennessee, 37916

  • CommonSpirit Saint Anthony Hospital Cancer Center

    Lakewood, Colorado, 80228

  • Rocky Mountain Cancer Centers-Lakewood

    Lakewood, Colorado, 80228

  • Saint Clare Hospital

    Lakewood, Washington, 98499

  • University Medical Center of Southern Nevada

    Las Vegas, Nevada, 89102

  • Sunrise Hospital and Medical Center

    Las Vegas, Nevada, 89109

  • Ann M Wierman MD LTD

    Las Vegas, Nevada, 89128

  • Alliance for Childhood Diseases/Cure 4 the Kids Foundation

    Las Vegas, Nevada, 89135

  • Summerlin Hospital Medical Center

    Las Vegas, Nevada, 89144

  • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

    Lebanon, New Hampshire, 03756

  • Saint Joseph Radiation Oncology Resource Center

    Lexington, Kentucky, 40504

  • CommonSpirit Saint Joseph Medical Center - East Lexington

    Lexington, Kentucky, 40509

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • Saint Elizabeth Regional Medical Center

    Lincoln, Nebraska, 68510

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202-3591

  • AdventHealth Littleton

    Littleton, Colorado, 80122

  • Loma Linda University Medical Center

    Loma Linda, California, 92354

  • CommonSpirit Saint Joseph Hospital London

    London, Kentucky, 40741

  • Miller Children's and Women's Hospital Long Beach

    Long Beach, California, 90806

  • Longmont United Hospital

    Longmont, Colorado, 80501

  • Rocky Mountain Cancer Centers-Longmont

    Longmont, Colorado, 80501

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Jewish Hospital

    Louisville, Kentucky, 40202

  • Norton Children's Hospital

    Louisville, Kentucky, 40202

  • Saints Mary and Elizabeth Hospital

    Louisville, Kentucky, 40215

  • UofL Health Medical Center Northeast

    Louisville, Kentucky, 40245

  • Covenant Children's Hospital

    Lubbock, Texas, 79410

  • UMC Cancer Center / UMC Health System

    Lubbock, Texas, 79415

  • Texas Tech University Health Sciences Center-Lubbock

    Lubbock, Texas, 79430

  • Valley Children's Hospital

    Madera, California, 93636

  • Saint Vincent Hospital Cancer Center at Marinette

    Marinette, Wisconsin, 54143

  • Marshfield Medical Center-Marshfield

    Marshfield, Wisconsin, 54449

  • Carle Physician Group-Mattoon/Charleston

    Mattoon, Illinois, 61938

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • Saint Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Banner Children's at Desert

    Mesa, Arizona, 85202

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • Nicklaus Children's Hospital

    Miami, Florida, 33155

  • Franciscan Saint Anthony Health-Michigan City

    Michigan City, Indiana, 46360

  • Woodland Cancer Care Center

    Michigan City, Indiana, 46360

  • Children's Hospital of Wisconsin

    Milwaukee, Wisconsin, 53226

  • NYU Langone Hospital - Long Island

    Mineola, New York, 11501

  • Children's Hospitals and Clinics of Minnesota - Minneapolis

    Minneapolis, Minnesota, 55404

  • University of Minnesota/Masonic Cancer Center

    Minneapolis, Minnesota, 55455

  • USA Health Strada Patient Care Center

    Mobile, Alabama, 36604

  • West Virginia University Healthcare

    Morgantown, West Virginia, 26506

  • Morristown Medical Center

    Morristown, New Jersey, 07960

  • SSM Health Good Samaritan

    Mount Vernon, Illinois, 62864

  • Trinity Health Muskegon Hospital

    Muskegon, Michigan, 49444

  • The Children's Hospital at TriStar Centennial

    Nashville, Tennessee, 37203

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Saint Peter's University Hospital

    New Brunswick, New Jersey, 08901

  • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

    New Brunswick, New Jersey, 08903

  • Yale University

    New Haven, Connecticut, 06520

  • The Steven and Alexandra Cohen Children's Medical Center of New York

    New Hyde Park, New York, 11040

  • Children's Hospital New Orleans

    New Orleans, Louisiana, 70118

  • Ochsner Medical Center Jefferson

    New Orleans, Louisiana, 70121

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone

    New York, New York, 10016

  • Mount Sinai Hospital

    New York, New York, 10029

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Newark Beth Israel Medical Center

    Newark, New Jersey, 07112

  • Chancellor Center for Oncology

    Newburgh, Indiana, 47630

  • Corewell Health Lakeland Hospitals - Niles Hospital

    Niles, Michigan, 49120

  • Children's Hospital of The King's Daughters

    Norfolk, Virginia, 23507

  • Advocate Children's Hospital-Oak Lawn

    Oak Lawn, Illinois, 60453

  • UCSF Benioff Children's Hospital Oakland

    Oakland, California, 94609

  • Kaiser Permanente-Oakland

    Oakland, California, 94611

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Mercy Hospital Oklahoma City

    Oklahoma City, Oklahoma, 73120

  • Children's Hospital and Medical Center of Omaha

    Omaha, Nebraska, 68114

  • Nebraska Medicine-Village Pointe

    Omaha, Nebraska, 68118

  • Alegent Health Immanuel Medical Center

    Omaha, Nebraska, 68122

  • Hematology and Oncology Consultants PC

    Omaha, Nebraska, 68122

  • Alegent Health Bergan Mercy Medical Center

    Omaha, Nebraska, 68124

  • Alegent Health Lakeside Hospital

    Omaha, Nebraska, 68130

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Memorial GYN Plus

    Ooltewah, Tennessee, 37363

  • Children's Hospital of Orange County

    Orange, California, 92868

  • AdventHealth Orlando

    Orlando, Florida, 32803

  • Arnold Palmer Hospital for Children

    Orlando, Florida, 32806

  • Nemours Children's Hospital

    Orlando, Florida, 32827

  • Hope Cancer Care of Nevada-Pahrump

    Pahrump, Nevada, 89048

  • Lucile Packard Children's Hospital Stanford University

    Palo Alto, California, 94304

  • Midlands Community Hospital

    Papillion, Nebraska, 68046

  • Advocate Children's Hospital-Park Ridge

    Park Ridge, Illinois, 60068

  • AdventHealth Parker

    Parker, Colorado, 80138

  • Rocky Mountain Cancer Centers-Parker

    Parker, Colorado, 80138

  • Saint Joseph's Regional Medical Center

    Paterson, New Jersey, 07503

  • Nemours Children's Clinic - Pensacola

    Pensacola, Florida, 32504

  • OSF Children's Hospital of Illinois

    Peoria, Illinois, 61637

  • Drexel University School of Medicine

    Philadelphia, Pennsylvania, 19102

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Saint Christopher's Hospital for Children

    Philadelphia, Pennsylvania, 19134

  • Phoenix Childrens Hospital

    Phoenix, Arizona, 85016

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • Huron Medical Center PC

    Port Huron, Michigan, 48060

  • Lake Huron Medical Center

    Port Huron, Michigan, 48060

  • Legacy Emanuel Children's Hospital

    Portland, Oregon, 97227

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Naval Medical Center - Portsmouth

    Portsmouth, Virginia, 23708-2197

  • Harrison HealthPartners Hematology and Oncology-Poulsbo

    Poulsbo, Washington, 98370

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • Saint Mary Corwin Medical Center

    Pueblo, Colorado, 81004

  • Rocky Mountain Cancer Centers - Pueblo

    Pueblo, Colorado, 81008

  • Corewell Health Reed City Hospital

    Reed City, Michigan, 49677

  • Renown Regional Medical Center

    Reno, Nevada, 89502

  • Saint Mary's Regional Medical Center

    Reno, Nevada, 89503

  • Radiation Oncology Associates

    Reno, Nevada, 89509

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

  • Carilion Children's

    Roanoke, Virginia, 24014

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • University of Rochester

    Rochester, New York, 14642

  • Mercy Clinic-Rolla-Cancer and Hematology

    Rolla, Missouri, 65401

  • Phelps Health Delbert Day Cancer Institute

    Rolla, Missouri, 65401

  • Corewell Health Children's

    Royal Oak, Michigan, 48073

  • Sutter Medical Center Sacramento

    Sacramento, California, 95816

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center

    Saint Joseph, Michigan, 49085

  • Corewell Health Lakeland Hospitals - Saint Joseph Hospital

    Saint Joseph, Michigan, 49085

  • Heartland Regional Medical Center

    Saint Joseph, Missouri, 64506

  • Primary Children's Hospital

    Salt Lake City, Utah, 84113

  • Children's Hospital of San Antonio

    San Antonio, Texas, 78207

  • Methodist Children's Hospital of South Texas

    San Antonio, Texas, 78229

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • Rady Children's Hospital - San Diego

    San Diego, California, 92123

  • UCSF Medical Center-Parnassus

    San Francisco, California, 94143

  • UCSF Medical Center-Mission Bay

    San Francisco, California, 94158

  • Memorial Health University Medical Center

    Savannah, Georgia, 31404

  • Maine Children's Cancer Program

    Scarborough, Maine, 04074

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Jewish Hospital Medical Center South

    Shepherdsville, Kentucky, 40165

  • Saint Joseph Medical Center Hematology and Oncology - Silverdale

    Silverdale, Washington, 98383

  • Sanford USD Medical Center - Sioux Falls

    Sioux Falls, South Dakota, 57117-5134

  • Providence Sacred Heart Medical Center and Children's Hospital

    Spokane, Washington, 99204

  • Saint John's Hospital

    Springfield, Illinois, 62702

  • Southern Illinois University School of Medicine

    Springfield, Illinois, 62702

  • Springfield Memorial Hospital

    Springfield, Illinois, 62781

  • Baystate Medical Center

    Springfield, Massachusetts, 01199

  • Mercy Hospital Springfield

    Springfield, Missouri, 65804

  • CoxHealth South Hospital

    Springfield, Missouri, 65807

  • Cardinal Glennon Children's Medical Center

    St Louis, Missouri, 63104

  • Mercy Infusion Center - Chippewa

    St Louis, Missouri, 63109

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Mercy Hospital Saint Louis

    St Louis, Missouri, 63141

  • Johns Hopkins All Children's Hospital

    St. Petersburg, Florida, 33701

  • Stony Brook University Medical Center

    Stony Brook, New York, 11794

  • State University of New York Upstate Medical University

    Syracuse, New York, 13210

  • Franciscan Research Center-Northwest Medical Plaza

    Tacoma, Washington, 98405

  • Mary Bridge Children's Hospital and Health Center

    Tacoma, Washington, 98405

  • Northwest Medical Specialties PLLC

    Tacoma, Washington, 98405

  • Madigan Army Medical Center

    Tacoma, Washington, 98431

  • Saint Joseph's Hospital/Children's Hospital-Tampa

    Tampa, Florida, 33607

  • Scott and White Memorial Hospital

    Temple, Texas, 76508

  • Montefiore Medical Center-Einstein Campus

    The Bronx, New York, 10461

  • Montefiore Medical Center-Weiler Hospital

    The Bronx, New York, 10461

  • Children's Hospital at Montefiore

    The Bronx, New York, 10467

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

  • Rocky Mountain Cancer Centers-Thornton

    Thornton, Colorado, 80260

  • ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital

    Toledo, Ohio, 43606

  • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

    Torrance, California, 90502

  • Munson Medical Center

    Traverse City, Michigan, 49684

  • Banner University Medical Center - Tucson

    Tucson, Arizona, 85719

  • Carle Cancer Center

    Urbana, Illinois, 61801

  • The Carle Foundation Hospital

    Urbana, Illinois, 61801

  • New York Medical College

    Valhalla, New York, 10595

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

  • Mercy Medical Center-West Lakes

    West Des Moines, Iowa, 50266

  • Saint Mary's Medical Center

    West Palm Beach, Florida, 33407

  • Alfred I duPont Hospital for Children

    Wilmington, Delaware, 19803

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

  • UMass Memorial Medical Center - University Campus

    Worcester, Massachusetts, 01655

  • Rush-Copley Healthcare Center

    Yorkville, Illinois, 60560

  • Onvida Health Yuma Medical Center

    Yuma, Arizona, 85364

Other trials in United States

Canada14 sites

  • Alberta Children's Hospital

    Calgary, Alberta, T3B 6A8

  • University of Alberta Hospital

    Edmonton, Alberta, T6G 2B7

  • IWK Health Centre

    Halifax, Nova Scotia, B3K 6R8

  • McMaster Children's Hospital at Hamilton Health Sciences

    Hamilton, Ontario, L8N 3Z5

  • Kingston Health Sciences Centre

    Kingston, Ontario, K7L 2V7

  • Children's Hospital

    London, Ontario, N6A 5W9

  • The Montreal Children's Hospital of the MUHC

    Montreal, Quebec, H3H 1P3

  • Centre Hospitalier Universitaire Sainte-Justine

    Montreal, Quebec, H3T 1C5

  • Children's Hospital of Eastern Ontario

    Ottawa, Ontario, K1H 8L1

  • CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)

    Québec, G1V 4G2

  • Janeway Child Health Centre

    St. John's, Newfoundland and Labrador, A1B 3V6

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

  • British Columbia Children's Hospital

    Vancouver, British Columbia, V6H 3V4

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

Puerto Rico2 sites

  • San Jorge Children's Hospital

    San Juan, 00912

  • University Pediatric Hospital

    San Juan, 00926

Other trials in Puerto Rico

About this study

Official title: Randomized Phase 3 Trial Evaluating the Addition of the IGF-1R Monoclonal Antibody Ganitumab (AMG 479, NSC# 750008) to Multiagent Chemotherapy for Patients With Newly Diagnosed Metastatic Ewing Sarcoma

This randomized phase III trial studies how well combination chemotherapy with or without ganitumab works in treating patients with newly diagnosed Ewing sarcoma that has spread to other parts of the body. Treatment with drugs that block the IGF-1R pathway, such as ganitumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether adding ganitumab to combination chemotherapy is more effective in treating patients with newly diagnosed metastatic Ewing sarcoma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine if event-free survival (EFS) in patients with newly diagnosed metastatic Ewing sarcoma treated with multiagent chemotherapy is improved with the addition of ganitumab (AMG 479).

SECONDARY OBJECTIVES:

  1. To describe the toxicity of the addition of ganitumab to multimodality therapy for patients with newly diagnosed metastatic Ewing sarcoma.

II. To compare overall survival in patients with newly diagnosed metastatic Ewing sarcoma treated with multiagent chemotherapy with and without the addition of ganitumab.

EXPLORATORY OBJECTIVES:

  1. To compare bone marrow response rates in patients with newly diagnosed metastatic Ewing sarcoma treated with multiagent chemotherapy with and without the addition of ganitumab.

II. To describe the toxicity of 6 months of ganitumab monotherapy as maintenance therapy following multimodality therapy in patients with newly diagnosed metastatic Ewing sarcoma.

III. To describe trough levels of ganitumab in a cohort of patients with Ewing sarcoma < 21 years of age treated with 18 mg/kg.

IV. To describe the feasibility of and local failure rates following hypofractionated stereotactic body radiotherapy (SBRT) directed at bone metastases in patients with newly diagnosed metastatic Ewing sarcoma.

  1. To determine if EFS, overall survival, bone marrow response rates, and toxicity differ based on serum markers of the insulin-like growth factor 1 (IGF-1) pathway in patients with newly diagnosed metastatic Ewing sarcoma treated with interval compressed chemotherapy with and without the addition of ganitumab.

VI. To determine if EFS, overall survival, and bone marrow response rates differ based on protein, deoxyribose nucleic acid (DNA), and ribonucleic acid (RNA) marker in patients with newly diagnosed metastatic Ewing sarcoma treated with interval compressed chemotherapy with and without the addition of ganitumab.

VII. To evaluate bone marrow micrometastatic disease and tumor cell surface IGF-1R expression at diagnosis and after 3 and 6 cycles of study therapy in patients with newly diagnosed metastatic Ewing sarcoma.

VIII. To determine if the presence of germline polymorphisms in EGFR correlate with response to multiagent therapy with and without ganitumab.

IX. To investigate the ability of fludeoxyglucose F 18-positron emission tomography (FDG-PET) to augment conventional response assessment of primary Ewing sarcoma tumors by magnetic resonance imaging (MRI).

  1. To explore FDG-PET response at the primary tumor as a prognostic marker and as a predictive biomarker of clinical activity of IGF-1R inhibition in patients with newly diagnosed metastatic Ewing sarcoma.

XI. To collect data on institutional testing for Ewing sarcoma breakpoint region 1 (EWSR1) translocation status in patients enrolling on study.

XII. To explore the capacity of plasma cell-free DNA analysis to detect tumor-specific genetic changes at initial diagnosis and after initiation of protocol therapy.

XIII. To collect a population of bone marrow metastatic tumor cells by flow cytometry for genomic profiling.

OUTLINE: Patients are randomized to 1 of 2 treatment regimens. (As of 3/20/2019, the study is closed to accrual and patients in Regimen B no longer receive ganitumab.)

REGIMEN A (vincristine sulfate, doxorubicin hydrochloride and cyclophosphamide [VDC] and ifosfamide and etoposide phosphate [IE]):

INDUCTION THERAPY: Patients receive vincristine sulfate intravenously (IV) over 1 minute on day 1, doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2, and cyclophosphamide IV over 30-60 minutes on day 1 of weeks 1, 5, and 9, and ifosfamide IV over 1 hour on days 1 to 5 and etoposide phosphate IV over 1-2 hours on days 1 to 5 of weeks 3, 7, and 11.

LOCAL CONTROL THERAPY: Between weeks 13-18, patients undergo surgery and/or radiation therapy.

CONSOLIDATION THERAPY: Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1, 7, 9, and 13; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2 of weeks 1 and 7, cyclophosphamide IV over 30-60 minutes on day 1 of weeks 1, 7, 9, and 13, ifosfamide IV over 1 hour on days 1 to 5 of weeks 3, 5, 11, and 15, and etoposide phosphate IV over 1-2 hours on days 1 to 5 of weeks 3, 5, 11, and 15.

METASTATIC SITE IRRADIATION: Patients with lung metastases undergo whole lung radiation and patients with bone metastases undergo definitive SBRT or external beam radiation therapy (EBRT).

REGIMEN B (VDC/IE + ganitumab):

INDUCTION THERAPY: Patients receive Induction therapy as in Regimen A and receive ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 of weeks 1, 3, 5, 7, 9, and 11.

LOCAL CONTROL THERAPY: Between weeks 13-18, patients undergo surgery and/or radiation therapy.

CONSOLIDATION THERAPY: Patients receive Consolidation therapy as in Regimen A and receive ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 of weeks 7, 9, 11, 13, and 15.

METASTATIC SITE IRRADIATION: Patients with lung metastases undergo whole lung radiation and patients with bone metastases undergo definitive SBRT or EBRT.

MAINTENANCE: Patients receive ganitumab IV over 30-60 minutes or 60-120 minutes every 3 weeks for 8 cycles.

After completion of study treatment, patients are followed for 10 years.

Medical subject headings
Sarcoma, Ewing

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518

    Given IV

  • DoxorubicinDrug

    Also called Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin

    Given IV

  • Doxorubicin HydrochlorideDrug

    Also called 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin

    Given IV

  • EtoposideDrug

    Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar

    Given IV

  • Etoposide PhosphateDrug

    Also called Etopophos

    Given IV

  • External Beam Radiation TherapyRadiation

    Also called Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam Radiotherapy

    Undergo EBRT

  • GanitumabBiological

    Also called AMG 479, AMG-479, AMG479, Anti-IGF-1R Human Monoclonal Antibody AMG-479

    Given IV

  • IfosfamideDrug

    Also called Asta Z 4942, Asta Z-4942, Cyfos, Holoxan

    Given IV

  • Stereotactic RadiosurgeryRadiation

    Also called SRS, Stereotactic External Beam Irradiation, stereotactic external-beam radiation therapy, Stereotactic Radiation Therapy

    Undergo SBRT

  • Therapeutic Surgical ProcedureProcedure or surgery

    Undergo surgery

  • VincristineDrug

    Also called LCR, Leurocristine, VCR, Vincrystine

    Given IV

  • Vincristine SulfateDrug

    Also called Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin

    Given IV

Study groups in NCT02306161
Study groupRoleWhat they receive
Regimen A (VDC/IE)ExperimentalSee Design Details.
Receives: Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Doxorubicin Hydrochloride; Drug: Etoposide; Drug: Etoposide Phosphate; Radiation: External Beam Radiation Therapy; Drug: Ifosfamide; Radiation: Stereotactic Radiosurgery; Procedure: Therapeutic Surgical Procedure; Drug: Vincristine; Drug: Vincristine Sulfate
Regimen B (VDC/IE + ganitumab)ExperimentalINDUCTION THERAPY: Patients receive Induction therapy as in Regimen A and receive ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 of weeks 1, 3, 5, 7, 9, and 11. LOCAL CONTROL THERAPY: Between weeks 13-18, patients undergo surgery and/or radiation therapy. CONSOLIDATION THERAPY: Patients receive Consolidation therapy as in Regimen A and receive ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 of weeks 7, 9, 11, 13, and 15. METASTATIC SITE IRRADIATION: Patients with lung metastases undergo whole lung radiation and patients with bone metastases undergo definitive SBRT or EBRT. MAINTENANCE: Patients receive ganitumab IV over 30-60 minutes or 60-120 minutes every 3 weeks for 8 cycles.
Receives: Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Doxorubicin Hydrochloride; Drug: Etoposide; Drug: Etoposide Phosphate; Radiation: External Beam Radiation Therapy; Biological: Ganitumab; Drug: Ifosfamide; Radiation: Stereotactic Radiosurgery; Procedure: Therapeutic Surgical Procedure; Drug: Vincristine; Drug: Vincristine Sulfate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event-free Survival

    Estimated 5-year EFS where EFS is calculated as the time from study enrollment to disease progression, disease relapse, occurrence of a second malignant neoplasm, death from any cause or last follow-up whichever occurs first. Kaplan-Meier method is used for estimation. Patients without an event are censored at last contact.

    Measured: 5 years after enrollment

Secondary outcomes (2)

  1. Overall Survival

    Time from study enrollment to death or last patient contact.

    Measured: 5 years after enrollment

  2. Frequency of Toxicity-events

    The number of induction or consolidation reporting periods in which a CTC version 4 codeable grade 4 or greater non-hematological adverse event, grade 3 or greater left ventricular systolic dysfunction or the reporting period is terminated because of a CTC codeable event.

    Measured: Up to 202 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Dec 2014 (estimated)
  2. Study start12 Dec 2014
  3. Primary completion31 Mar 2021
  4. Study completion16 Sep 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
312 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02306161
Sponsor's protocol ID
NCI-2014-02380
Other IDs
NCI-2014-02380, AEWS1221, s15-00442, AEWS1221, AEWS1221, U10CA098543, U10CA180886
Status last verified
Sep 2026
First submitted
1 Dec 2014
Last updated
22 Oct 2026
Data monitoring committee
No

Publications

  • von Kruchten R, DelRocco NJ, Adams LC, Singh SB, Varniab ZS, Bender JG, Krailo MD, DuBois S, Daldrup-Link HE. Role of diffusion-weighted MRI in assessing Ewing sarcoma treatment response: Findings from a COG phase III trial. Magn Reson Imaging. 2026 Oct;132:110706. doi: 10.1016/j.mri.2026.110706. Epub 2026 May 27.

    PubMed 42208702

  • DuBois SG, Krailo MD, Glade-Bender J, Buxton A, Laack N, Randall RL, Chen HX, Seibel NL, Boron M, Terezakis S, Hill-Kayser C, Hayes A, Reid JM, Teot L, Rakheja D, Womer R, Arndt C, Lessnick SL, Crompton BD, Kolb EA, Daldrup-Link H, Eutsler E, Reed DR, Janeway KA, Gorlick RG. Randomized Phase III Trial of Ganitumab With Interval-Compressed Chemotherapy for Patients With Newly Diagnosed Metastatic Ewing Sarcoma: A Report From the Children's Oncology Group. J Clin Oncol. 2023 Apr 10;41(11):2098-2107. doi: 10.1200/JCO.22.01815. Epub 2023 Jan 20.

    PubMed 36669140

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