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

March 21, 2024 updated by: National Cancer Institute (NCI)

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. 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:

I. 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:

I. 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.

V. 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).

X. 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.

Study Type

Interventional

Enrollment (Actual)

312

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
      • Quebec, Canada, G1V 4G2
        • CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
    • Alberta
      • Calgary, Alberta, Canada, T3B 6A8
        • Alberta Children's Hospital
      • Edmonton, Alberta, Canada, T6G 2B7
        • University of Alberta Hospital
    • British Columbia
      • Vancouver, British Columbia, Canada, V6H 3V4
        • British Columbia Children's Hospital
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 0V9
        • CancerCare Manitoba
    • Newfoundland and Labrador
      • Saint John's, Newfoundland and Labrador, Canada, A1B 3V6
        • Janeway Child Health Centre
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3K 6R8
        • IWK Health Centre
    • Ontario
      • Hamilton, Ontario, Canada, L8N 3Z5
        • McMaster Children's Hospital at Hamilton Health Sciences
      • Kingston, Ontario, Canada, K7L 2V7
        • Kingston Health Sciences Centre
      • London, Ontario, Canada, N6A 5W9
        • Children's Hospital
      • Ottawa, Ontario, Canada, K1H 8L1
        • Children's Hospital of Eastern Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Hospital for Sick Children
    • Quebec
      • Montreal, Quebec, Canada, H3H 1P3
        • The Montreal Children's Hospital of the MUHC
      • Montreal, Quebec, Canada, H3T 1C5
        • Centre Hospitalier Universitaire Sainte-Justine
  • Puerto Rico
      • San Juan, Puerto Rico, 00926
        • University Pediatric Hospital
      • San Juan, Puerto Rico, 00912
        • San Jorge Children's Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Children's Hospital of Alabama
      • Mobile, Alabama, United States, 36604
        • USA Health Strada Patient Care Center
    • Alaska
      • Anchorage, Alaska, United States, 99508
        • Providence Alaska Medical Center
    • Arizona
      • Mesa, Arizona, United States, 85202
        • Banner Children's at Desert
      • Phoenix, Arizona, United States, 85016
        • Phoenix Childrens Hospital
      • Tucson, Arizona, United States, 85719
        • Banner University Medical Center - Tucson
      • Yuma, Arizona, United States, 85364
        • Yuma Regional Medical Center
    • Arkansas
      • Hot Springs, Arkansas, United States, 71913
        • CHI Saint Vincent Cancer Center Hot Springs
      • Little Rock, Arkansas, United States, 72202-3591
        • Arkansas Children's Hospital
    • California
      • Downey, California, United States, 90242
        • Kaiser Permanente Downey Medical Center
      • Duarte, California, United States, 91010
        • City of Hope Comprehensive Cancer Center
      • Loma Linda, California, United States, 92354
        • Loma Linda University Medical Center
      • Long Beach, California, United States, 90806
        • Miller Children's and Women's Hospital Long Beach
      • Los Angeles, California, United States, 90027
        • Children's Hospital Los Angeles
      • Madera, California, United States, 93636
        • Valley Children's Hospital
      • Oakland, California, United States, 94609
        • UCSF Benioff Children's Hospital Oakland
      • Oakland, California, United States, 94611
        • Kaiser Permanente-Oakland
      • Orange, California, United States, 92868
        • Children's Hospital of Orange County
      • Palo Alto, California, United States, 94304
        • Lucile Packard Children's Hospital Stanford University
      • Sacramento, California, United States, 95816
        • Sutter Medical Center Sacramento
      • Sacramento, California, United States, 95817
        • University of California Davis Comprehensive Cancer Center
      • San Diego, California, United States, 92123
        • Rady Children's Hospital - San Diego
      • San Francisco, California, United States, 94158
        • UCSF Medical Center-Mission Bay
      • San Francisco, California, United States, 94143
        • UCSF Medical Center-Parnassus
      • Torrance, California, United States, 90502
        • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado
      • Colorado Springs, Colorado, United States, 80907
        • Penrose-Saint Francis Healthcare
      • Colorado Springs, Colorado, United States, 80907
        • Rocky Mountain Cancer Centers-Penrose
      • Denver, Colorado, United States, 80210
        • Porter Adventist Hospital
      • Denver, Colorado, United States, 80218
        • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
      • Durango, Colorado, United States, 81301
        • Mercy Medical Center
      • Durango, Colorado, United States, 81301
        • Southwest Oncology PC
      • Golden, Colorado, United States, 80401
        • Mountain Blue Cancer Care Center
      • Lakewood, Colorado, United States, 80228
        • Saint Anthony Hospital
      • Lakewood, Colorado, United States, 80228
        • Rocky Mountain Cancer Centers-Lakewood
      • Littleton, Colorado, United States, 80122
        • Littleton Adventist Hospital
      • Longmont, Colorado, United States, 80501
        • Longmont United Hospital
      • Longmont, Colorado, United States, 80501
        • Rocky Mountain Cancer Centers-Longmont
      • Parker, Colorado, United States, 80138
        • Parker Adventist Hospital
      • Parker, Colorado, United States, 80138
        • Rocky Mountain Cancer Centers-Parker
      • Pueblo, Colorado, United States, 81004
        • Saint Mary Corwin Medical Center
      • Pueblo, Colorado, United States, 81008
        • Rocky Mountain Cancer Centers - Pueblo
      • Thornton, Colorado, United States, 80260
        • Rocky Mountain Cancer Centers-Thornton
    • Connecticut
      • Hartford, Connecticut, United States, 06106
        • Connecticut Children's Medical Center
      • New Haven, Connecticut, United States, 06520
        • Yale University
    • Delaware
      • Wilmington, Delaware, United States, 19803
        • Alfred I duPont Hospital for Children
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Children's National Medical Center
      • Washington, District of Columbia, United States, 20007
        • MedStar Georgetown University Hospital
    • Florida
      • Fort Myers, Florida, United States, 33908
        • Golisano Children's Hospital of Southwest Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida Health Science Center - Gainesville
      • Hollywood, Florida, United States, 33021
        • Memorial Regional Hospital/Joe DiMaggio Children's Hospital
      • Jacksonville, Florida, United States, 32207
        • Nemours Children's Clinic-Jacksonville
      • Miami, Florida, United States, 33155
        • Nicklaus Children's Hospital
      • Miami, Florida, United States, 33136
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
      • Orlando, Florida, United States, 32827
        • Nemours Children's Hospital
      • Orlando, Florida, United States, 32803
        • AdventHealth Orlando
      • Orlando, Florida, United States, 32806
        • Arnold Palmer Hospital for Children
      • Pensacola, Florida, United States, 32504
        • Nemours Children's Clinic - Pensacola
      • Saint Petersburg, Florida, United States, 33701
        • Johns Hopkins All Children's Hospital
      • Tampa, Florida, United States, 33607
        • Saint Joseph's Hospital/Children's Hospital-Tampa
      • West Palm Beach, Florida, United States, 33407
        • Saint Mary's Hospital
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Children's Healthcare of Atlanta - Egleston
      • Augusta, Georgia, United States, 30912
        • Augusta University Medical Center
      • Savannah, Georgia, United States, 31404
        • Memorial Health University Medical Center
    • Hawaii
      • Honolulu, Hawaii, United States, 96813
        • Straub Clinic and Hospital
      • Honolulu, Hawaii, United States, 96826
        • Kapiolani Medical Center for Women and Children
      • Honolulu, Hawaii, United States, 96819
        • Kaiser Permanente Moanalua Medical Center
    • Idaho
      • Boise, Idaho, United States, 83712
        • Saint Luke's Cancer Institute - Boise
    • Illinois
      • Aurora, Illinois, United States, 60504
        • Rush - Copley Medical Center
      • Chicago, Illinois, United States, 60637
        • University of Chicago Comprehensive Cancer Center
      • Chicago, Illinois, United States, 60612
        • University of Illinois
      • Chicago, Illinois, United States, 60611
        • Lurie Children's Hospital-Chicago
      • Danville, Illinois, United States, 61832
        • Carle at The Riverfront
      • Effingham, Illinois, United States, 62401
        • Carle Physician Group-Effingham
      • Mattoon, Illinois, United States, 61938
        • Carle Physician Group-Mattoon/Charleston
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center
      • Mount Vernon, Illinois, United States, 62864
        • Good Samaritan Regional Health Center
      • Oak Lawn, Illinois, United States, 60453
        • Advocate Children's Hospital-Oak Lawn
      • Park Ridge, Illinois, United States, 60068
        • Advocate Children's Hospital-Park Ridge
      • Peoria, Illinois, United States, 61637
        • Saint Jude Midwest Affiliate
      • Springfield, Illinois, United States, 62781
        • Memorial Medical Center
      • Springfield, Illinois, United States, 62702
        • Southern Illinois University School of Medicine
      • Springfield, Illinois, United States, 62702
        • Saint John's Hospital
      • Urbana, Illinois, United States, 61801
        • Carle Cancer Center
      • Urbana, Illinois, United States, 61801
        • The Carle Foundation Hospital
      • Yorkville, Illinois, United States, 60560
        • Rush-Copley Healthcare Center
    • Indiana
      • Evansville, Indiana, United States, 47713
        • Deaconess Clinic Downtown
      • Indianapolis, Indiana, United States, 46202
        • Riley Hospital for Children
      • Indianapolis, Indiana, United States, 46260
        • Ascension Saint Vincent Indianapolis Hospital
      • Michigan City, Indiana, United States, 46360
        • Franciscan Saint Anthony Health-Michigan City
      • Michigan City, Indiana, United States, 46360
        • Woodland Cancer Care Center
      • Newburgh, Indiana, United States, 47630
        • Chancellor Center for Oncology
    • Iowa
      • Clive, Iowa, United States, 50325
        • Mercy Cancer Center-West Lakes
      • Clive, Iowa, United States, 50325
        • Medical Oncology and Hematology Associates-West Des Moines
      • Council Bluffs, Iowa, United States, 51503
        • Alegent Health Mercy Hospital
      • Creston, Iowa, United States, 50801
        • Greater Regional Medical Center
      • Des Moines, Iowa, United States, 50314
        • Mercy Medical Center - Des Moines
      • Des Moines, Iowa, United States, 50309
        • Blank Children's Hospital
      • Des Moines, Iowa, United States, 50314
        • Mission Cancer and Blood - Laurel
      • Iowa City, Iowa, United States, 52242
        • University of Iowa/Holden Comprehensive Cancer Center
      • West Des Moines, Iowa, United States, 50266
        • Mercy Medical Center-West Lakes
    • Kentucky
      • Bardstown, Kentucky, United States, 40004
        • Flaget Memorial Hospital
      • Corbin, Kentucky, United States, 40701
        • Commonwealth Cancer Center-Corbin
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky/Markey Cancer Center
      • Lexington, Kentucky, United States, 40504
        • Saint Joseph Radiation Oncology Resource Center
      • Lexington, Kentucky, United States, 40509
        • Saint Joseph Hospital East
      • London, Kentucky, United States, 40741
        • Saint Joseph London
      • Louisville, Kentucky, United States, 40202
        • Jewish Hospital
      • Louisville, Kentucky, United States, 40202
        • Norton Children's Hospital
      • Louisville, Kentucky, United States, 40245
        • UofL Health Medical Center Northeast
      • Louisville, Kentucky, United States, 40215
        • Saints Mary and Elizabeth Hospital
      • Shepherdsville, Kentucky, United States, 40165
        • Jewish Hospital Medical Center South
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Medical Center Jefferson
      • New Orleans, Louisiana, United States, 70118
        • Children's Hospital New Orleans
    • Maine
      • Bangor, Maine, United States, 04401
        • Eastern Maine Medical Center
      • Scarborough, Maine, United States, 04074
        • Maine Children's Cancer Program
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University/Sidney Kimmel Cancer Center
      • Baltimore, Maryland, United States, 21215
        • Sinai Hospital of Baltimore
      • Baltimore, Maryland, United States, 21201
        • University of Maryland/Greenebaum Cancer Center
      • Bethesda, Maryland, United States, 20889-5600
        • Walter Reed National Military Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Cancer Center
      • Springfield, Massachusetts, United States, 01199
        • Baystate Medical Center
      • Worcester, Massachusetts, United States, 01655
        • UMass Memorial Medical Center - University Campus
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Comprehensive Cancer Center
      • Ann Arbor, Michigan, United States, 48109
        • C S Mott Children's Hospital
      • Battle Creek, Michigan, United States, 49017
        • Bronson Battle Creek
      • Detroit, Michigan, United States, 48201
        • Wayne State University/Karmanos Cancer Institute
      • Detroit, Michigan, United States, 48236
        • Ascension Saint John Hospital
      • Flint, Michigan, United States, 48503
        • Hurley Medical Center
      • Grand Rapids, Michigan, United States, 49503
        • Spectrum Health at Butterworth Campus
      • Grand Rapids, Michigan, United States, 49503
        • Helen DeVos Children's Hospital at Spectrum Health
      • Grand Rapids, Michigan, United States, 49503
        • Trinity Health Grand Rapids Hospital
      • Kalamazoo, Michigan, United States, 49007
        • West Michigan Cancer Center
      • Kalamazoo, Michigan, United States, 49007
        • Bronson Methodist Hospital
      • Kalamazoo, Michigan, United States, 49048
        • Borgess Medical Center
      • Muskegon, Michigan, United States, 49444
        • Trinity Health Muskegon Hospital
      • Niles, Michigan, United States, 49120
        • Corewell Health Lakeland Hospitals - Niles Hospital
      • Port Huron, Michigan, United States, 48060
        • Lake Huron Medical Center
      • Port Huron, Michigan, United States, 48060
        • Huron Medical Center PC
      • Reed City, Michigan, United States, 49677
        • Corewell Health Reed City Hospital
      • Royal Oak, Michigan, United States, 48073
        • Beaumont Children's Hospital-Royal Oak
      • Saint Joseph, Michigan, United States, 49085
        • Lakeland Medical Center Saint Joseph
      • Saint Joseph, Michigan, United States, 49085
        • Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
      • Traverse City, Michigan, United States, 49684
        • Munson Medical Center
    • Minnesota
      • Duluth, Minnesota, United States, 55805
        • Essentia Health Cancer Center
      • Minneapolis, Minnesota, United States, 55404
        • Children's Hospitals and Clinics of Minnesota - Minneapolis
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota/Masonic Cancer Center
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • Missouri
      • Bolivar, Missouri, United States, 65613
        • Central Care Cancer Center - Bolivar
      • Branson, Missouri, United States, 65616
        • Cox Cancer Center Branson
      • Columbia, Missouri, United States, 65201
        • Columbia Regional
      • Joplin, Missouri, United States, 64804
        • Freeman Health System
      • Joplin, Missouri, United States, 64804
        • Mercy Hospital Joplin
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Hospitals and Clinics
      • Rolla, Missouri, United States, 65401
        • Delbert Day Cancer Institute at PCRMC
      • Rolla, Missouri, United States, 65401
        • Mercy Clinic-Rolla-Cancer and Hematology
      • Saint Joseph, Missouri, United States, 64506
        • Heartland Regional Medical Center
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
      • Saint Louis, Missouri, United States, 63141
        • Mercy Hospital Saint Louis
      • Saint Louis, Missouri, United States, 63104
        • Cardinal Glennon Children's Medical Center
      • Saint Louis, Missouri, United States, 63109
        • Saint Louis Cancer and Breast Institute-South City
      • Springfield, Missouri, United States, 65807
        • CoxHealth South Hospital
      • Springfield, Missouri, United States, 65804
        • Mercy Hospital Springfield
    • Nebraska
      • Bellevue, Nebraska, United States, 68123
        • Nebraska Medicine-Bellevue
      • Grand Island, Nebraska, United States, 68803
        • CHI Health Saint Francis
      • Kearney, Nebraska, United States, 68847
        • CHI Health Good Samaritan
      • Kearney, Nebraska, United States, 68845
        • Heartland Hematology and Oncology
      • Lincoln, Nebraska, United States, 68510
        • Saint Elizabeth Regional Medical Center
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
      • Omaha, Nebraska, United States, 68124
        • Alegent Health Bergan Mercy Medical Center
      • Omaha, Nebraska, United States, 68118
        • Nebraska Medicine-Village Pointe
      • Omaha, Nebraska, United States, 68122
        • Alegent Health Immanuel Medical Center
      • Omaha, Nebraska, United States, 68130
        • Alegent Health Lakeside Hospital
      • Omaha, Nebraska, United States, 68131
        • Creighton University Medical Center
      • Omaha, Nebraska, United States, 68114
        • Children's Hospital and Medical Center of Omaha
      • Omaha, Nebraska, United States, 68122
        • Hematology and Oncology Consultants PC
      • Papillion, Nebraska, United States, 68046
        • Midlands Community Hospital
    • Nevada
      • Carson City, Nevada, United States, 89703
        • Carson Tahoe Regional Medical Center
      • Henderson, Nevada, United States, 89052
        • Comprehensive Cancer Centers of Nevada-Horizon Ridge
      • Las Vegas, Nevada, United States, 89144
        • Summerlin Hospital Medical Center
      • Las Vegas, Nevada, United States, 89109
        • Sunrise Hospital and Medical Center
      • Las Vegas, Nevada, United States, 89135
        • Alliance for Childhood Diseases/Cure 4 the Kids Foundation
      • Las Vegas, Nevada, United States, 89102
        • University Medical Center of Southern Nevada
      • Las Vegas, Nevada, United States, 89128
        • Ann M Wierman MD LTD
      • Pahrump, Nevada, United States, 89048
        • Hope Cancer Care of Nevada-Pahrump
      • Reno, Nevada, United States, 89502
        • Renown Regional Medical Center
      • Reno, Nevada, United States, 89503
        • Saint Mary's Regional Medical Center
      • Reno, Nevada, United States, 89509
        • Radiation Oncology Associates
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
      • Morristown, New Jersey, United States, 07960
        • Morristown Medical Center
      • New Brunswick, New Jersey, United States, 08901
        • Saint Peter's University Hospital
      • New Brunswick, New Jersey, United States, 08903
        • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
      • Newark, New Jersey, United States, 07112
        • Newark Beth Israel Medical Center
      • Paterson, New Jersey, United States, 07503
        • Saint Joseph's Regional Medical Center
    • New York
      • Albany, New York, United States, 12208
        • Albany Medical Center
      • Bronx, New York, United States, 10461
        • Montefiore Medical Center-Einstein Campus
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center - Moses Campus
      • Bronx, New York, United States, 10461
        • Montefiore Medical Center-Weiler Hospital
      • Bronx, New York, United States, 10467
        • Children's Hospital at Montefiore
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • Glens Falls, New York, United States, 12801
        • Glens Falls Hospital
      • Mineola, New York, United States, 11501
        • NYU Winthrop Hospital
      • New Hyde Park, New York, United States, 11040
        • The Steven and Alexandra Cohen Children's Medical Center of New York
      • New York, New York, United States, 10029
        • Mount Sinai Hospital
      • New York, New York, United States, 10032
        • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
      • New York, New York, United States, 10016
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone
      • Rochester, New York, United States, 14642
        • University of Rochester
      • Stony Brook, New York, United States, 11794
        • Stony Brook University Medical Center
      • Syracuse, New York, United States, 13210
        • State University of New York Upstate Medical University
      • Valhalla, New York, United States, 10595
        • New York Medical College
    • North Carolina
      • Asheville, North Carolina, United States, 28801
        • Mission Hospital
      • Chapel Hill, North Carolina, United States, 27599
        • UNC Lineberger Comprehensive Cancer Center
      • Charlotte, North Carolina, United States, 28203
        • Carolinas Medical Center/Levine Cancer Institute
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences
    • North Dakota
      • Fargo, North Dakota, United States, 58122
        • Sanford Broadway Medical Center
    • Ohio
      • Akron, Ohio, United States, 44308
        • Children's Hospital Medical Center of Akron
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
      • Cincinnati, Ohio, United States, 45220
        • Good Samaritan Hospital - Cincinnati
      • Cincinnati, Ohio, United States, 45242
        • Bethesda North Hospital
      • Cincinnati, Ohio, United States, 45247
        • TriHealth Cancer Institute-Westside
      • Cincinnati, Ohio, United States, 45255
        • TriHealth Cancer Institute-Anderson
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
      • Cleveland, Ohio, United States, 44106
        • Rainbow Babies and Childrens Hospital
      • Columbus, Ohio, United States, 43205
        • Nationwide Children's Hospital
      • Dayton, Ohio, United States, 45404
        • Dayton Children's Hospital
      • Toledo, Ohio, United States, 43606
        • ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
      • Oklahoma City, Oklahoma, United States, 73120
        • Mercy Hospital Oklahoma City
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
      • Portland, Oregon, United States, 97227
        • Legacy Emanuel Children's Hospital
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18103
        • Lehigh Valley Hospital-Cedar Crest
      • Bethlehem, Pennsylvania, United States, 18017
        • Lehigh Valley Hospital - Muhlenberg
      • Danville, Pennsylvania, United States, 17822
        • Geisinger Medical Center
      • Hershey, Pennsylvania, United States, 17033
        • Penn State Children's Hospital
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
      • Philadelphia, Pennsylvania, United States, 19134
        • Saint Christopher's Hospital for Children
      • Philadelphia, Pennsylvania, United States, 19102
        • Drexel University School of Medicine
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburgh of UPMC
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
      • Columbia, South Carolina, United States, 29203
        • Prisma Health Richland Hospital
      • Greenville, South Carolina, United States, 29607
        • Saint Francis Cancer Center
      • Greenville, South Carolina, United States, 29601
        • Saint Francis Hospital
      • Greenville, South Carolina, United States, 29605
        • BI-LO Charities Children's Cancer Center
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57117-5134
        • Sanford USD Medical Center - Sioux Falls
    • Tennessee
      • Chattanooga, Tennessee, United States, 37403
        • T C Thompson Children's Hospital
      • Chattanooga, Tennessee, United States, 37404
        • Memorial Hospital
      • Hixson, Tennessee, United States, 37343
        • Pulmonary Medicine Center of Chattanooga-Hixson
      • Knoxville, Tennessee, United States, 37916
        • East Tennessee Childrens Hospital
      • Memphis, Tennessee, United States, 38105
        • Saint Jude Children's Research Hospital
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University/Ingram Cancer Center
      • Nashville, Tennessee, United States, 37203
        • The Children's Hospital at TriStar Centennial
      • Ooltewah, Tennessee, United States, 37363
        • Memorial GYN Plus
    • Texas
      • Austin, Texas, United States, 78723
        • Dell Children's Medical Center of Central Texas
      • Bryan, Texas, United States, 77802
        • Saint Joseph Regional Cancer Center
      • Corpus Christi, Texas, United States, 78411
        • Driscoll Children's Hospital
      • Dallas, Texas, United States, 75390
        • UT Southwestern/Simmons Cancer Center-Dallas
      • Dallas, Texas, United States, 75230
        • Medical City Dallas Hospital
      • El Paso, Texas, United States, 79905
        • El Paso Children's Hospital
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
      • Lubbock, Texas, United States, 79410
        • Covenant Children's Hospital
      • Lubbock, Texas, United States, 79415
        • UMC Cancer Center / UMC Health System
      • Lubbock, Texas, United States, 79430
        • Texas Tech University Health Sciences Center-Lubbock
      • San Antonio, Texas, United States, 78229
        • University of Texas Health Science Center at San Antonio
      • San Antonio, Texas, United States, 78207
        • Children's Hospital of San Antonio
      • San Antonio, Texas, United States, 78229
        • Methodist Children's Hospital of South Texas
      • Temple, Texas, United States, 76508
        • Scott and White Memorial Hospital
    • Utah
      • Salt Lake City, Utah, United States, 84113
        • Primary Children's Hospital
    • Vermont
      • Berlin, Vermont, United States, 05602
        • Central Vermont Medical Center/National Life Cancer Treatment
      • Burlington, Vermont, United States, 05401
        • University of Vermont Medical Center
      • Burlington, Vermont, United States, 05405
        • University of Vermont and State Agricultural College
    • Virginia
      • Falls Church, Virginia, United States, 22042
        • Inova Fairfax Hospital
      • Norfolk, Virginia, United States, 23507
        • Children's Hospital of The King's Daughters
      • Portsmouth, Virginia, United States, 23708-2197
        • Naval Medical Center - Portsmouth
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University/Massey Cancer Center
      • Roanoke, Virginia, United States, 24014
        • Carilion Children's
    • Washington
      • Bremerton, Washington, United States, 98310
        • Harrison HealthPartners Hematology and Oncology-Bremerton
      • Bremerton, Washington, United States, 98310
        • Harrison Medical Center
      • Burien, Washington, United States, 98166
        • Highline Medical Center-Main Campus
      • Enumclaw, Washington, United States, 98022
        • Saint Elizabeth Hospital
      • Federal Way, Washington, United States, 98003
        • Saint Francis Hospital
      • Lakewood, Washington, United States, 98499
        • Saint Clare Hospital
      • Poulsbo, Washington, United States, 98370
        • Harrison HealthPartners Hematology and Oncology-Poulsbo
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital
      • Spokane, Washington, United States, 99204
        • Providence Sacred Heart Medical Center and Children's Hospital
      • Tacoma, Washington, United States, 98405
        • Mary Bridge Children's Hospital and Health Center
      • Tacoma, Washington, United States, 98405
        • Northwest Medical Specialties PLLC
      • Tacoma, Washington, United States, 98431
        • Madigan Army Medical Center
      • Tacoma, Washington, United States, 98405
        • Franciscan Research Center-Northwest Medical Plaza
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • West Virginia University Healthcare
    • Wisconsin
      • Green Bay, Wisconsin, United States, 54301
        • Saint Vincent Hospital Cancer Center Green Bay
      • Green Bay, Wisconsin, United States, 54301-3526
        • Green Bay Oncology at Saint Vincent Hospital
      • Marinette, Wisconsin, United States, 54143
        • Saint Vincent Hospital Cancer Center at Marinette
      • Marshfield, Wisconsin, United States, 54449
        • Marshfield Medical Center-Marshfield
      • Milwaukee, Wisconsin, United States, 53226
        • Children's Hospital of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 50 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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:

      • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Regimen A (VDC/IE)
See Design Details.
Drug: Etoposide
Given IV
Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16
  • VP 16-213
  • VP-16
  • VP-16-213
  • VP16
  • VP 16213
Drug: Ifosfamide
Given IV
Other Names:
  • Asta Z 4942
  • Asta Z-4942
  • Cyfos
  • Holoxan
  • Holoxane
  • Ifex
  • IFO
  • IFO-Cell
  • Ifolem
  • Ifomida
  • Ifomide
  • Ifosfamidum
  • Ifoxan
  • IFX
  • Iphosphamid
  • Iphosphamide
  • Iso-Endoxan
  • Isoendoxan
  • Isophosphamide
  • Mitoxana
  • MJF 9325
  • MJF-9325
  • Naxamide
  • Seromida
  • Tronoxal
  • Z 4942
  • Z-4942
Drug: Cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • CTX
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamide Monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
  • Asta B 518
  • B-518
  • WR-138719
Drug: Vincristine Sulfate
Given IV
Other Names:
  • Oncovin
  • Kyocristine
  • Leurocristine Sulfate
  • Leurocristine, sulfate
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate
Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
  • Adriamycin
  • 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 Hydrochloride
  • Adriamycin PFS
  • Adriamycin RDF
  • ADRIAMYCIN, HYDROCHLORIDE
  • Adriamycine
  • Adriblastina
  • Adriblastine
  • Adrimedac
  • Chloridrato de Doxorrubicina
  • DOX
  • DOXO-CELL
  • Doxolem
  • Doxorubicin HCl
  • Doxorubicin.HCl
  • Doxorubin
  • Farmiblastina
  • FI 106
  • FI-106
  • hydroxydaunorubicin
  • Rubex
Radiation: External Beam Radiation Therapy
Undergo EBRT
Other Names:
  • EBRT
  • Definitive Radiation Therapy
  • External Beam Radiation
  • External Beam Radiotherapy
  • External Beam RT
  • external radiation
  • External Radiation Therapy
  • external-beam radiation
  • Radiation, External Beam
  • Teleradiotherapy
  • Teletherapy
  • Teletherapy Radiation
  • External Beam Radiotherapy (conventional)
Drug: Vincristine
Given IV
Other Names:
  • VCR
  • Leurocristine
  • Vincrystine
  • LCR
Drug: Etoposide Phosphate
Given IV
Other Names:
  • Etopophos
Drug: Doxorubicin
Given IV
Other Names:
  • Adriablastin
  • Hydroxydaunomycin
  • Hydroxyl Daunorubicin
  • Hydroxyldaunorubicin
Radiation: Stereotactic Radiosurgery
Undergo SBRT
Other Names:
  • Stereotactic External Beam Irradiation
  • stereotactic external-beam radiation therapy
  • Stereotactic Radiotherapy
  • stereotaxic radiation therapy
  • stereotaxic radiosurgery
  • Stereotactic Radiation Therapy
  • SRS
Procedure: Therapeutic Surgical Procedure
Undergo surgery
Experimental: 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.
Drug: Etoposide
Given IV
Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16
  • VP 16-213
  • VP-16
  • VP-16-213
  • VP16
  • VP 16213
Drug: Ifosfamide
Given IV
Other Names:
  • Asta Z 4942
  • Asta Z-4942
  • Cyfos
  • Holoxan
  • Holoxane
  • Ifex
  • IFO
  • IFO-Cell
  • Ifolem
  • Ifomida
  • Ifomide
  • Ifosfamidum
  • Ifoxan
  • IFX
  • Iphosphamid
  • Iphosphamide
  • Iso-Endoxan
  • Isoendoxan
  • Isophosphamide
  • Mitoxana
  • MJF 9325
  • MJF-9325
  • Naxamide
  • Seromida
  • Tronoxal
  • Z 4942
  • Z-4942
Drug: Cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • CTX
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamide Monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
  • Asta B 518
  • B-518
  • WR-138719
Drug: Vincristine Sulfate
Given IV
Other Names:
  • Oncovin
  • Kyocristine
  • Leurocristine Sulfate
  • Leurocristine, sulfate
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate
Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
  • Adriamycin
  • 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 Hydrochloride
  • Adriamycin PFS
  • Adriamycin RDF
  • ADRIAMYCIN, HYDROCHLORIDE
  • Adriamycine
  • Adriblastina
  • Adriblastine
  • Adrimedac
  • Chloridrato de Doxorrubicina
  • DOX
  • DOXO-CELL
  • Doxolem
  • Doxorubicin HCl
  • Doxorubicin.HCl
  • Doxorubin
  • Farmiblastina
  • FI 106
  • FI-106
  • hydroxydaunorubicin
  • Rubex
Radiation: External Beam Radiation Therapy
Undergo EBRT
Other Names:
  • EBRT
  • Definitive Radiation Therapy
  • External Beam Radiation
  • External Beam Radiotherapy
  • External Beam RT
  • external radiation
  • External Radiation Therapy
  • external-beam radiation
  • Radiation, External Beam
  • Teleradiotherapy
  • Teletherapy
  • Teletherapy Radiation
  • External Beam Radiotherapy (conventional)
Drug: Vincristine
Given IV
Other Names:
  • VCR
  • Leurocristine
  • Vincrystine
  • LCR
Drug: Etoposide Phosphate
Given IV
Other Names:
  • Etopophos
Drug: Doxorubicin
Given IV
Other Names:
  • Adriablastin
  • Hydroxydaunomycin
  • Hydroxyl Daunorubicin
  • Hydroxyldaunorubicin
Radiation: Stereotactic Radiosurgery
Undergo SBRT
Other Names:
  • Stereotactic External Beam Irradiation
  • stereotactic external-beam radiation therapy
  • Stereotactic Radiotherapy
  • stereotaxic radiation therapy
  • stereotaxic radiosurgery
  • Stereotactic Radiation Therapy
  • SRS
Procedure: Therapeutic Surgical Procedure
Undergo surgery
Biological: Ganitumab
Given IV
Other Names:
  • AMG 479
  • Anti-IGF-1R Human Monoclonal Antibody AMG-479

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free Survival
Time Frame: 5 years after enrollment
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.
5 years after enrollment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: 5 years after enrollment
Time from study enrollment to death or last patient contact.
5 years after enrollment
Frequency of Toxicity-events
Time Frame: Up to 202 days
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.
Up to 202 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum IGF Pathway Component and Tissue Protein, Deoxyribonucleic Acid (DNA), and Ribonucleic Acid Markers
Time Frame: Up to 10 years
In addition to the log rank test the modeling approach will be used for the primary study comparison. Linear trend in EFS-risk will be investigated by segregating the marker level according to quartiles. For bone marrow response rate analyses, Fisher's exact test will be used to compare the objective bone marrow response rate (complete response vs. incomplete response) at start of local control between patients with biomarker levels above and below the group median.
Up to 10 years
Tumor Cell Surface IGF-1R Expression
Time Frame: Up to 307 days
Extent of tumor cell IGF-1R co-expression will also be reported. Change in tumor cell IGF-1R co-expression in patients treated with and without ganitumab will be reported descriptively.
Up to 307 days
Germline Polymorphisms in EGFR
Time Frame: Up to 10 years
EFS will be compared between patients with and without the presence of the minor allele using the log rank test, both for the entire patient population and for patients randomized to ganitumab.
Up to 10 years
EWS Translocation
Time Frame: Up to 10 years
The institutional result of EWS tumor testing will be categorized as translocation detected (yes v. no) and the type of translocation detected will also be recorded. The proportion of patients with a particular EWS translocation variant will be tabulated.
Up to 10 years
Circulating Tumor DNA (ctDNA) Testing
Time Frame: Up to 202 days
Will report the proportion of patients that have a change in translocation result associated with ctDNA testing across time periods.
Up to 202 days
Serial Genomic Profiling
Time Frame: Up to 307 days
Will be identified by flow cytometry. Profiles will be presented graphically, and samples obtained from different sites of tumor within the same individual will also be presented.
Up to 307 days
Occurrence of Sinusoidal Obstructive Disease (SOS) Associated With the Addition of Ganitumab to VDC/IE
Time Frame: Up to 202 days
The number of induction and maintenance cycles received by patients randomized to the experimental therapy where SOS is observed. Only patients who receive all reporting period therapy or experience SOS will contribute to this outcome measure.
Up to 202 days
Frequency of Resolution of Bone Marrow Metastases
Time Frame: Up to 84 days
The number of patients who are enrolled with bone marrow metastases whose bone marrow disease is not detected after evaluation at the time of of first local control measure or the end of the Induction reporting period, whichever comes first. Only eligible patients who receive at least one dose of randomized treatment assignment will be considered for this measure.
Up to 84 days
Frequency of Toxicity Events During Ganitumab Maintenance
Time Frame: Up to 307 days
The number of induction or consolidation reporting periods in which a CTC version 4 codeable non-hematological adverse event, grade 3 left ventricular systolic dysfunction or the reporting period is terminated because of a CTC codeable event.
Up to 307 days
Trough Levels of Serum Ganitumab
Time Frame: Up to 15 days
Trough levels of serum ganitumab prior to the second dose of ganitumab during induction obtained will be categorized as less than 10 micrograms per milliliter or greater than or equal to 10 micrograms per milliliter. This analysis will be conducted for the first 10 eligible patients who receive ganitumab.
Up to 15 days
Proportion of Patients Who Successfully Receive Planned Stereotactic Body Radiotherapy (SBRT)
Time Frame: 202 days
A patient who has SBRT planned for at least one metastatic site and receives successful SBRT treatment to at least 85% of metastatic sites in the treatment plan. Successful treatment is determined by IROC review criteria. Only eligible patients start the metastatic site radiation reporting period will be considered for this outcome measure.
202 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Steven G DuBois, Children's Oncology Group

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 12, 2014

Primary Completion (Actual)

March 31, 2021

Study Completion (Estimated)

September 22, 2024

Study Registration Dates

First Submitted

December 1, 2014

First Submitted That Met QC Criteria

December 1, 2014

First Posted (Estimated)

December 3, 2014

Study Record Updates

Last Update Posted (Actual)

March 22, 2024

Last Update Submitted That Met QC Criteria

March 21, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2014-02380 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA180886 (U.S. NIH Grant/Contract)
  • U10CA098543 (U.S. NIH Grant/Contract)
  • AEWS1221 (Other Identifier: CTEP)
  • s15-00442

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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