Metastatic Ewing SarcomaMetastatic Malignant Neoplasm in the BoneMetastatic Malignant Neoplasm in the Bone MarrowMetastatic Malignant Neoplasm in the LungMetastatic Peripheral Primitive Neuroectodermal Tumor of BonePeripheral Primitive Neuroectodermal Tumor of Soft Tissues
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.
Eligibility
Sex
ALL
Min age
—
Max age
50 Years
Healthy volunteers
No
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
Primary outcome measure(s)
Event-free Survival — 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.
Trial sites (314)
Facility
City
Region
Status
Children's Hospital of Alabama
Birmingham
Alabama
USA Health Strada Patient Care Center
Mobile
Alabama
Providence Alaska Medical Center
Anchorage
Alaska
Banner Children's at Desert
Mesa
Arizona
Phoenix Childrens Hospital
Phoenix
Arizona
Banner University Medical Center - Tucson
Tucson
Arizona
Onvida Health Yuma Medical Center
Yuma
Arizona
CHI Saint Vincent Cancer Center Hot Springs
Hot Springs
Arkansas
Arkansas Children's Hospital
Little Rock
Arkansas
Kaiser Permanente Downey Medical Center
Downey
California
City of Hope Comprehensive Cancer Center
Duarte
California
Loma Linda University Medical Center
Loma Linda
California
Miller Children's and Women's Hospital Long Beach
Long Beach
California
Children's Hospital Los Angeles
Los Angeles
California
Valley Children's Hospital
Madera
California
UCSF Benioff Children's Hospital Oakland
Oakland
California
Kaiser Permanente-Oakland
Oakland
California
Children's Hospital of Orange County
Orange
California
Lucile Packard Children's Hospital Stanford University
Palo Alto
California
Sutter Medical Center Sacramento
Sacramento
California
University of California Davis Comprehensive Cancer Center
Sacramento
California
Rady Children's Hospital - San Diego
San Diego
California
UCSF Medical Center-Parnassus
San Francisco
California
UCSF Medical Center-Mission Bay
San Francisco
California
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance
California
Children's Hospital Colorado
Aurora
Colorado
Penrose-Saint Francis Healthcare
Colorado Springs
Colorado
Rocky Mountain Cancer Centers-Penrose
Colorado Springs
Colorado
AdventHealth Porter
Denver
Colorado
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver
Colorado
CommonSpirit Cancer Center Mercy
Durango
Colorado
Mercy Medical Center
Durango
Colorado
Mountain Blue Cancer Care Center
Golden
Colorado
CommonSpirit Saint Anthony Hospital Cancer Center
Lakewood
Colorado
Rocky Mountain Cancer Centers-Lakewood
Lakewood
Colorado
AdventHealth Littleton
Littleton
Colorado
Longmont United Hospital
Longmont
Colorado
Rocky Mountain Cancer Centers-Longmont
Longmont
Colorado
AdventHealth Parker
Parker
Colorado
Rocky Mountain Cancer Centers-Parker
Parker
Colorado
+ 274 more sites — see the full list on the official registry below.
More National Cancer Institute (NCI) trials in Canada
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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