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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT02306161
Other study ID # NCI-2014-02380
Secondary ID NCI-2014-02380AE
Status Active, not recruiting
Phase Phase 3
First received
Last updated
Start date December 12, 2014
Est. completion date September 22, 2024

Study information

Verified date March 2024
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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. 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.


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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 312
Est. completion date September 22, 2024
Est. primary completion date March 31, 2021
Accepts healthy volunteers No
Gender All
Age group N/A to 50 Years
Eligibility 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 Design


Related Conditions & MeSH terms


Intervention

Drug:
Cyclophosphamide
Given IV
Doxorubicin
Given IV
Doxorubicin Hydrochloride
Given IV
Etoposide
Given IV
Etoposide Phosphate
Given IV
Radiation:
External Beam Radiation Therapy
Undergo EBRT
Biological:
Ganitumab
Given IV
Drug:
Ifosfamide
Given IV
Radiation:
Stereotactic Radiosurgery
Undergo SBRT
Procedure:
Therapeutic Surgical Procedure
Undergo surgery
Drug:
Vincristine
Given IV
Vincristine Sulfate
Given IV

Locations

Country Name City State
Canada Alberta Children's Hospital Calgary Alberta
Canada University of Alberta Hospital Edmonton Alberta
Canada IWK Health Centre Halifax Nova Scotia
Canada McMaster Children's Hospital at Hamilton Health Sciences Hamilton Ontario
Canada Kingston Health Sciences Centre Kingston Ontario
Canada Children's Hospital London Ontario
Canada Centre Hospitalier Universitaire Sainte-Justine Montreal Quebec
Canada The Montreal Children's Hospital of the MUHC Montreal Quebec
Canada Children's Hospital of Eastern Ontario Ottawa Ontario
Canada CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL) Quebec
Canada Janeway Child Health Centre Saint John's Newfoundland and Labrador
Canada Hospital for Sick Children Toronto Ontario
Canada British Columbia Children's Hospital Vancouver British Columbia
Canada CancerCare Manitoba Winnipeg Manitoba
Puerto Rico San Jorge Children's Hospital San Juan
Puerto Rico University Pediatric Hospital San Juan
United States Children's Hospital Medical Center of Akron Akron Ohio
United States Albany Medical Center Albany New York
United States Lehigh Valley Hospital-Cedar Crest Allentown Pennsylvania
United States Providence Alaska Medical Center Anchorage Alaska
United States C S Mott Children's Hospital Ann Arbor Michigan
United States University of Michigan Comprehensive Cancer Center Ann Arbor Michigan
United States Mission Hospital Asheville North Carolina
United States Children's Healthcare of Atlanta - Egleston Atlanta Georgia
United States Augusta University Medical Center Augusta Georgia
United States Children's Hospital Colorado Aurora Colorado
United States Rush - Copley Medical Center Aurora Illinois
United States Dell Children's Medical Center of Central Texas Austin Texas
United States Johns Hopkins University/Sidney Kimmel Cancer Center Baltimore Maryland
United States Sinai Hospital of Baltimore Baltimore Maryland
United States University of Maryland/Greenebaum Cancer Center Baltimore Maryland
United States Eastern Maine Medical Center Bangor Maine
United States Flaget Memorial Hospital Bardstown Kentucky
United States Bronson Battle Creek Battle Creek Michigan
United States Nebraska Medicine-Bellevue Bellevue Nebraska
United States Central Vermont Medical Center/National Life Cancer Treatment Berlin Vermont
United States Walter Reed National Military Medical Center Bethesda Maryland
United States Lehigh Valley Hospital - Muhlenberg Bethlehem Pennsylvania
United States Children's Hospital of Alabama Birmingham Alabama
United States Saint Luke's Cancer Institute - Boise Boise Idaho
United States Central Care Cancer Center - Bolivar Bolivar Missouri
United States Dana-Farber Cancer Institute Boston Massachusetts
United States Massachusetts General Hospital Cancer Center Boston Massachusetts
United States Cox Cancer Center Branson Branson Missouri
United States Harrison HealthPartners Hematology and Oncology-Bremerton Bremerton Washington
United States Children's Hospital at Montefiore Bronx New York
United States Montefiore Medical Center - Moses Campus Bronx New York
United States Montefiore Medical Center-Einstein Campus Bronx New York
United States Montefiore Medical Center-Weiler Hospital Bronx New York
United States Saint Joseph Regional Cancer Center Bryan Texas
United States Roswell Park Cancer Institute Buffalo New York
United States Highline Medical Center-Main Campus Burien Washington
United States University of Vermont and State Agricultural College Burlington Vermont
United States University of Vermont Medical Center Burlington Vermont
United States Carson Tahoe Regional Medical Center Carson City Nevada
United States UNC Lineberger Comprehensive Cancer Center Chapel Hill North Carolina
United States Medical University of South Carolina Charleston South Carolina
United States Carolinas Medical Center/Levine Cancer Institute Charlotte North Carolina
United States Memorial Hospital Chattanooga Tennessee
United States T C Thompson Children's Hospital Chattanooga Tennessee
United States Lurie Children's Hospital-Chicago Chicago Illinois
United States University of Chicago Comprehensive Cancer Center Chicago Illinois
United States University of Illinois Chicago Illinois
United States Bethesda North Hospital Cincinnati Ohio
United States Cincinnati Children's Hospital Medical Center Cincinnati Ohio
United States Good Samaritan Hospital - Cincinnati Cincinnati Ohio
United States TriHealth Cancer Institute-Anderson Cincinnati Ohio
United States TriHealth Cancer Institute-Westside Cincinnati Ohio
United States Cleveland Clinic Foundation Cleveland Ohio
United States Rainbow Babies and Childrens Hospital Cleveland Ohio
United States Mercy Cancer Center-West Lakes Clive Iowa
United States Mission Cancer and Blood - West Des Moines Clive Iowa
United States Penrose-Saint Francis Healthcare Colorado Springs Colorado
United States Rocky Mountain Cancer Centers-Penrose Colorado Springs Colorado
United States Columbia Regional Columbia Missouri
United States Prisma Health Richland Hospital Columbia South Carolina
United States Nationwide Children's Hospital Columbus Ohio
United States Commonwealth Cancer Center-Corbin Corbin Kentucky
United States Driscoll Children's Hospital Corpus Christi Texas
United States Alegent Health Mercy Hospital Council Bluffs Iowa
United States Greater Regional Medical Center Creston Iowa
United States Medical City Dallas Hospital Dallas Texas
United States UT Southwestern/Simmons Cancer Center-Dallas Dallas Texas
United States Carle at The Riverfront Danville Illinois
United States Geisinger Medical Center Danville Pennsylvania
United States Dayton Children's Hospital Dayton Ohio
United States Porter Adventist Hospital Denver Colorado
United States Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center Denver Colorado
United States Blank Children's Hospital Des Moines Iowa
United States Mercy Medical Center - Des Moines Des Moines Iowa
United States Mission Cancer and Blood - Laurel Des Moines Iowa
United States Ascension Saint John Hospital Detroit Michigan
United States Wayne State University/Karmanos Cancer Institute Detroit Michigan
United States Kaiser Permanente Downey Medical Center Downey California
United States City of Hope Comprehensive Cancer Center Duarte California
United States Essentia Health Cancer Center Duluth Minnesota
United States Mercy Medical Center Durango Colorado
United States Southwest Oncology PC Durango Colorado
United States Duke University Medical Center Durham North Carolina
United States Carle Physician Group-Effingham Effingham Illinois
United States El Paso Children's Hospital El Paso Texas
United States Saint Elizabeth Hospital Enumclaw Washington
United States Deaconess Clinic Downtown Evansville Indiana
United States Inova Fairfax Hospital Falls Church Virginia
United States Sanford Broadway Medical Center Fargo North Dakota
United States Saint Francis Hospital Federal Way Washington
United States Hurley Medical Center Flint Michigan
United States Golisano Children's Hospital of Southwest Florida Fort Myers Florida
United States Cook Children's Medical Center Fort Worth Texas
United States University of Florida Health Science Center - Gainesville Gainesville Florida
United States Glens Falls Hospital Glens Falls New York
United States Mountain Blue Cancer Care Center Golden Colorado
United States Nebraska Cancer Specialists/Oncology Hematology West PC Grand Island Nebraska
United States Corewell Health Grand Rapids Hospitals - Butterworth Hospital Grand Rapids Michigan
United States Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital Grand Rapids Michigan
United States Trinity Health Grand Rapids Hospital Grand Rapids Michigan
United States Green Bay Oncology at Saint Vincent Hospital Green Bay Wisconsin
United States Saint Vincent Hospital Cancer Center Green Bay Green Bay Wisconsin
United States BI-LO Charities Children's Cancer Center Greenville South Carolina
United States Saint Francis Cancer Center Greenville South Carolina
United States Saint Francis Hospital Greenville South Carolina
United States Hackensack University Medical Center Hackensack New Jersey
United States Connecticut Children's Medical Center Hartford Connecticut
United States Comprehensive Cancer Centers of Nevada-Horizon Ridge Henderson Nevada
United States Penn State Children's Hospital Hershey Pennsylvania
United States Pulmonary Medicine Center of Chattanooga-Hixson Hixson Tennessee
United States Memorial Regional Hospital/Joe DiMaggio Children's Hospital Hollywood Florida
United States Kaiser Permanente Moanalua Medical Center Honolulu Hawaii
United States Kapiolani Medical Center for Women and Children Honolulu Hawaii
United States Straub Clinic and Hospital Honolulu Hawaii
United States CHI Saint Vincent Cancer Center Hot Springs Hot Springs Arkansas
United States Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center Houston Texas
United States M D Anderson Cancer Center Houston Texas
United States Ascension Saint Vincent Indianapolis Hospital Indianapolis Indiana
United States Riley Hospital for Children Indianapolis Indiana
United States University of Iowa/Holden Comprehensive Cancer Center Iowa City Iowa
United States University of Mississippi Medical Center Jackson Mississippi
United States Nemours Children's Clinic-Jacksonville Jacksonville Florida
United States Freeman Health System Joplin Missouri
United States Mercy Hospital Joplin Joplin Missouri
United States Borgess Medical Center Kalamazoo Michigan
United States Bronson Methodist Hospital Kalamazoo Michigan
United States West Michigan Cancer Center Kalamazoo Michigan
United States Children's Mercy Hospitals and Clinics Kansas City Missouri
United States CHI Health Good Samaritan Kearney Nebraska
United States Heartland Hematology and Oncology Kearney Nebraska
United States East Tennessee Childrens Hospital Knoxville Tennessee
United States Rocky Mountain Cancer Centers-Lakewood Lakewood Colorado
United States Saint Anthony Hospital Lakewood Colorado
United States Saint Clare Hospital Lakewood Washington
United States Alliance for Childhood Diseases/Cure 4 the Kids Foundation Las Vegas Nevada
United States Ann M Wierman MD LTD Las Vegas Nevada
United States Summerlin Hospital Medical Center Las Vegas Nevada
United States Sunrise Hospital and Medical Center Las Vegas Nevada
United States University Medical Center of Southern Nevada Las Vegas Nevada
United States Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center Lebanon New Hampshire
United States Saint Joseph Hospital East Lexington Kentucky
United States Saint Joseph Radiation Oncology Resource Center Lexington Kentucky
United States University of Kentucky/Markey Cancer Center Lexington Kentucky
United States Saint Elizabeth Regional Medical Center Lincoln Nebraska
United States Arkansas Children's Hospital Little Rock Arkansas
United States Littleton Adventist Hospital Littleton Colorado
United States Loma Linda University Medical Center Loma Linda California
United States Saint Joseph London London Kentucky
United States Miller Children's and Women's Hospital Long Beach Long Beach California
United States Longmont United Hospital Longmont Colorado
United States Rocky Mountain Cancer Centers-Longmont Longmont Colorado
United States Children's Hospital Los Angeles Los Angeles California
United States Jewish Hospital Louisville Kentucky
United States Norton Children's Hospital Louisville Kentucky
United States Saints Mary and Elizabeth Hospital Louisville Kentucky
United States UofL Health Medical Center Northeast Louisville Kentucky
United States Covenant Children's Hospital Lubbock Texas
United States Texas Tech University Health Sciences Center-Lubbock Lubbock Texas
United States UMC Cancer Center / UMC Health System Lubbock Texas
United States Valley Children's Hospital Madera California
United States Saint Vincent Hospital Cancer Center at Marinette Marinette Wisconsin
United States Marshfield Medical Center-Marshfield Marshfield Wisconsin
United States Carle Physician Group-Mattoon/Charleston Mattoon Illinois
United States Loyola University Medical Center Maywood Illinois
United States Saint Jude Children's Research Hospital Memphis Tennessee
United States Banner Children's at Desert Mesa Arizona
United States Nicklaus Children's Hospital Miami Florida
United States University of Miami Miller School of Medicine-Sylvester Cancer Center Miami Florida
United States Franciscan Saint Anthony Health-Michigan City Michigan City Indiana
United States Woodland Cancer Care Center Michigan City Indiana
United States Children's Hospital of Wisconsin Milwaukee Wisconsin
United States NYU Langone Hospital - Long Island Mineola New York
United States Children's Hospitals and Clinics of Minnesota - Minneapolis Minneapolis Minnesota
United States University of Minnesota/Masonic Cancer Center Minneapolis Minnesota
United States USA Health Strada Patient Care Center Mobile Alabama
United States West Virginia University Healthcare Morgantown West Virginia
United States Morristown Medical Center Morristown New Jersey
United States Good Samaritan Regional Health Center Mount Vernon Illinois
United States Trinity Health Muskegon Hospital Muskegon Michigan
United States The Children's Hospital at TriStar Centennial Nashville Tennessee
United States Vanderbilt University/Ingram Cancer Center Nashville Tennessee
United States Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital New Brunswick New Jersey
United States Saint Peter's University Hospital New Brunswick New Jersey
United States Yale University New Haven Connecticut
United States The Steven and Alexandra Cohen Children's Medical Center of New York New Hyde Park New York
United States Children's Hospital New Orleans New Orleans Louisiana
United States Ochsner Medical Center Jefferson New Orleans Louisiana
United States Laura and Isaac Perlmutter Cancer Center at NYU Langone New York New York
United States Mount Sinai Hospital New York New York
United States NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center New York New York
United States Newark Beth Israel Medical Center Newark New Jersey
United States Chancellor Center for Oncology Newburgh Indiana
United States Corewell Health Lakeland Hospitals - Niles Hospital Niles Michigan
United States Children's Hospital of The King's Daughters Norfolk Virginia
United States Advocate Children's Hospital-Oak Lawn Oak Lawn Illinois
United States Kaiser Permanente-Oakland Oakland California
United States UCSF Benioff Children's Hospital Oakland Oakland California
United States Mercy Hospital Oklahoma City Oklahoma City Oklahoma
United States University of Oklahoma Health Sciences Center Oklahoma City Oklahoma
United States Alegent Health Bergan Mercy Medical Center Omaha Nebraska
United States Alegent Health Immanuel Medical Center Omaha Nebraska
United States Alegent Health Lakeside Hospital Omaha Nebraska
United States Children's Hospital and Medical Center of Omaha Omaha Nebraska
United States Creighton University Medical Center Omaha Nebraska
United States Hematology and Oncology Consultants PC Omaha Nebraska
United States Nebraska Medicine-Village Pointe Omaha Nebraska
United States University of Nebraska Medical Center Omaha Nebraska
United States Memorial GYN Plus Ooltewah Tennessee
United States Children's Hospital of Orange County Orange California
United States AdventHealth Orlando Orlando Florida
United States Arnold Palmer Hospital for Children Orlando Florida
United States Nemours Children's Hospital Orlando Florida
United States Hope Cancer Care of Nevada-Pahrump Pahrump Nevada
United States Lucile Packard Children's Hospital Stanford University Palo Alto California
United States Midlands Community Hospital Papillion Nebraska
United States Advocate Children's Hospital-Park Ridge Park Ridge Illinois
United States Parker Adventist Hospital Parker Colorado
United States Rocky Mountain Cancer Centers-Parker Parker Colorado
United States Saint Joseph's Regional Medical Center Paterson New Jersey
United States Nemours Children's Clinic - Pensacola Pensacola Florida
United States Saint Jude Midwest Affiliate Peoria Illinois
United States Children's Hospital of Philadelphia Philadelphia Pennsylvania
United States Drexel University School of Medicine Philadelphia Pennsylvania
United States Saint Christopher's Hospital for Children Philadelphia Pennsylvania
United States Phoenix Childrens Hospital Phoenix Arizona
United States Children's Hospital of Pittsburgh of UPMC Pittsburgh Pennsylvania
United States Huron Medical Center PC Port Huron Michigan
United States Lake Huron Medical Center Port Huron Michigan
United States Legacy Emanuel Children's Hospital Portland Oregon
United States Oregon Health and Science University Portland Oregon
United States Naval Medical Center - Portsmouth Portsmouth Virginia
United States Harrison HealthPartners Hematology and Oncology-Poulsbo Poulsbo Washington
United States Rhode Island Hospital Providence Rhode Island
United States Rocky Mountain Cancer Centers - Pueblo Pueblo Colorado
United States Saint Mary Corwin Medical Center Pueblo Colorado
United States Corewell Health Reed City Hospital Reed City Michigan
United States Radiation Oncology Associates Reno Nevada
United States Renown Regional Medical Center Reno Nevada
United States Saint Mary's Regional Medical Center Reno Nevada
United States Virginia Commonwealth University/Massey Cancer Center Richmond Virginia
United States Carilion Children's Roanoke Virginia
United States Mayo Clinic in Rochester Rochester Minnesota
United States University of Rochester Rochester New York
United States Delbert Day Cancer Institute at PCRMC Rolla Missouri
United States Mercy Clinic-Rolla-Cancer and Hematology Rolla Missouri
United States Beaumont Children's Hospital-Royal Oak Royal Oak Michigan
United States Sutter Medical Center Sacramento Sacramento California
United States University of California Davis Comprehensive Cancer Center Sacramento California
United States Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center Saint Joseph Michigan
United States Corewell Health Lakeland Hospitals - Saint Joseph Hospital Saint Joseph Michigan
United States Heartland Regional Medical Center Saint Joseph Missouri
United States Cardinal Glennon Children's Medical Center Saint Louis Missouri
United States Mercy Hospital Saint Louis Saint Louis Missouri
United States Saint Louis Cancer and Breast Institute-South City Saint Louis Missouri
United States Washington University School of Medicine Saint Louis Missouri
United States Johns Hopkins All Children's Hospital Saint Petersburg Florida
United States Primary Children's Hospital Salt Lake City Utah
United States Children's Hospital of San Antonio San Antonio Texas
United States Methodist Children's Hospital of South Texas San Antonio Texas
United States University of Texas Health Science Center at San Antonio San Antonio Texas
United States Rady Children's Hospital - San Diego San Diego California
United States UCSF Medical Center-Mission Bay San Francisco California
United States UCSF Medical Center-Parnassus San Francisco California
United States Memorial Health University Medical Center Savannah Georgia
United States Maine Children's Cancer Program Scarborough Maine
United States Seattle Children's Hospital Seattle Washington
United States Jewish Hospital Medical Center South Shepherdsville Kentucky
United States Saint Michael Cancer Center Silverdale Washington
United States Sanford USD Medical Center - Sioux Falls Sioux Falls South Dakota
United States Providence Sacred Heart Medical Center and Children's Hospital Spokane Washington
United States Baystate Medical Center Springfield Massachusetts
United States CoxHealth South Hospital Springfield Missouri
United States Memorial Medical Center Springfield Illinois
United States Mercy Hospital Springfield Springfield Missouri
United States Saint John's Hospital Springfield Illinois
United States Southern Illinois University School of Medicine Springfield Illinois
United States Stony Brook University Medical Center Stony Brook New York
United States State University of New York Upstate Medical University Syracuse New York
United States Franciscan Research Center-Northwest Medical Plaza Tacoma Washington
United States Madigan Army Medical Center Tacoma Washington
United States Mary Bridge Children's Hospital and Health Center Tacoma Washington
United States Northwest Medical Specialties PLLC Tacoma Washington
United States Saint Joseph's Hospital/Children's Hospital-Tampa Tampa Florida
United States Scott and White Memorial Hospital Temple Texas
United States Rocky Mountain Cancer Centers-Thornton Thornton Colorado
United States ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital Toledo Ohio
United States Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center Torrance California
United States Munson Medical Center Traverse City Michigan
United States Banner University Medical Center - Tucson Tucson Arizona
United States Carle Cancer Center Urbana Illinois
United States The Carle Foundation Hospital Urbana Illinois
United States New York Medical College Valhalla New York
United States Children's National Medical Center Washington District of Columbia
United States MedStar Georgetown University Hospital Washington District of Columbia
United States Mercy Medical Center-West Lakes West Des Moines Iowa
United States Saint Mary's Hospital West Palm Beach Florida
United States Alfred I duPont Hospital for Children Wilmington Delaware
United States Wake Forest University Health Sciences Winston-Salem North Carolina
United States UMass Memorial Medical Center - University Campus Worcester Massachusetts
United States Rush-Copley Healthcare Center Yorkville Illinois
United States Yuma Regional Medical Center Yuma Arizona

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico, 

Outcome

Type Measure Description Time frame Safety issue
Other Serum IGF Pathway Component and Tissue Protein, Deoxyribonucleic Acid (DNA), and Ribonucleic Acid Markers 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
Other Tumor Cell Surface IGF-1R Expression 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
Other Germline Polymorphisms in EGFR 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
Other EWS Translocation 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
Other Circulating Tumor DNA (ctDNA) Testing Will report the proportion of patients that have a change in translocation result associated with ctDNA testing across time periods. Up to 202 days
Other Serial Genomic Profiling 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
Other Occurrence of Sinusoidal Obstructive Disease (SOS) Associated With the Addition of Ganitumab to VDC/IE 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
Other Frequency of Resolution of Bone Marrow Metastases 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
Other Frequency of Toxicity Events During Ganitumab Maintenance 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
Other Trough Levels of Serum Ganitumab 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
Other Proportion of Patients Who Successfully Receive Planned Stereotactic Body Radiotherapy (SBRT) 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
Primary 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. 5 years after enrollment
Secondary Overall Survival Time from study enrollment to death or last patient contact. 5 years after enrollment
Secondary 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. Up to 202 days
See also
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