Observation, Radiation Therapy, Combination Chemotherapy, and/or Surgery in Treating Young Patients With Soft Tissue Sarcoma

Stage IV Adult Soft Tissue Sarcoma Clinical Trial

Official title:

Risk-Based Treatment for Non-Rhabdomyosarcoma Soft Tissue Sarcomas (NRSTS) in Patients Under 30 Years of Age

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00346164
• Other study ID #: ARST0332
• Secondary ID: NCI-2009-00426CO
• Status: Completed
• Phase: Phase 3
• Start date: February 5, 2007
• Est. completion date: March 31, 2022

Study information

• Verified date: June 2021
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase III trial is studying observation to see how well a risk based treatment strategy works in patients with soft tissue sarcoma. In the study, patients are assigned to receive surgery +/- radiotherapy +/- chemotherapy depending on their risk of recurrence. Sometimes, after surgery, the tumor may not need additional treatment until it progresses. In this case, observation may be sufficient. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as ifosfamide and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery.

Description:

PRIMARY OBJECTIVES:

I. Define a risk-based treatment strategy comprising observation only, adjuvant radiotherapy, or adjuvant chemoradiotherapy or neoadjuvant chemoradiotherapy, surgery, and adjuvant chemotherapy with or without radiotherapy in young patients with non-rhabdomyosarcoma soft tissue sarcoma (NRSTS).

II. Assess event-free and overall survival of patients treated with these regimens.

III. Assess the pattern of treatment failure in these patients.

SECONDARY OBJECTIVES:

I. Assess the feasibility of a neoadjuvant chemoradiotherapy approach in patients with intermediate- or high-risk NRSTS.

II. Assess the imaging and pathologic responses to neoadjuvant chemoradiotherapy in patients with intermediate- or high-risk NRSTS.

III. Correlate imaging and pathologic response with clinical outcomes in patients with intermediate- or high-risk disease who undergo neoadjuvant chemoradiotherapy.

IV. Prospectively define clinical prognostic factors associated with event-free survival, overall survival, local recurrence, and distant recurrence in these patients.

V. Correlate patient outcomes with findings of biologic studies performed on tissue specimens collected on protocol COG-D9902 from these patients.

VI. Determine whether the diagnosis and histologic grade of NRSTS assigned by the enrolling institution correlates with the diagnosis and histologic grade established by central expert pathology reviewers.

VII. Compare the Pediatric Oncology Group (POG) and Fédération Nationale des Centres de Lutte Contre le Cancer (French Federation of Cancer Centers [FNCLCC]) pathologic grading systems to determine which better correlates with clinical outcomes.

OUTLINE: This is a multicenter study. Patients are divided into 3 risk groups according to presence of metastatic disease (yes vs no), status of prior surgery (resected vs unresected), grade of tumor (low vs high), and size of primary tumor (≤ 5 cm vs > 5 cm). Patients are assigned to different treatment regimens based on disease extent (nonmetastatic vs metastatic), tumor size (≤ 5 cm vs > 5 cm), extent of resection of primary tumor (resected vs unresected), extent of resection of metastases (complete or microscopic residual vs gross residual), microscopic tumor margins (negative vs positive), and tumor grade (low vs high).

GROUP 1 (low risk [nonmetastatic, grossly resected disease, except high-grade tumor > 5 cm]):

Patients with low-grade tumor with either negative or positive microscopic margins or high-grade tumor ≤ 5 cm (in maximum diameter) with negative microscopic margins are assigned to regimen A. Patients with high-grade tumor ≤ 5 cm (in maximum diameter) with positive microscopic margins are assigned to regimen B.

REGIMEN A (observation only): Patients undergo observation only.

REGIMEN B (adjuvant radiotherapy): Beginning between 6-42 days after surgical resection, patients undergo a total of 31 fractions of adjuvant radiotherapy.

GROUP 2 (intermediate risk [nonmetastatic, resected or unresected disease]): Patients with grossly resected, high-grade tumor > 5 cm (in maximum diameter) are assigned to regimen C. Patients with unresected tumor are assigned to regimen D.

REGIMEN C (adjuvant chemoradiotherapy): Patients receive ifosfamide IV over 3 hours on days 1-3 in weeks 1, 4, 7, 10, 13, and 16 and doxorubicin hydrochloride IV over 24 hours on days 1 and 2 in weeks 1, 4, 13, 16, and 19. Beginning in week 4, patients also undergo a total of 31 fractions of radiotherapy.

*NOTE: *Patients who receive brachytherapy will initiate radiotherapy in Week 1. If brachytherapy is administered, chemotherapy should begin within 2 weeks of completion of brachytherapy and the Weeks 1 and 19 doxorubicin should be given instead at Weeks 7 and 10.

REGIMEN D (neoadjuvant chemoradiotherapy, surgery, and adjuvant chemotherapy with or without radiotherapy): Neoadjuvant chemoradiotherapy and surgery: Patients receive ifosfamide IV over 3 hours on days 1-3 in weeks 1, 4, 7, and 10 and doxorubicin hydrochloride IV over 24 hours on days 1 and 2 in weeks 1 and 4. Beginning in week 4, patients also undergo a total of 31 fractions of radiotherapy**. Patients undergo surgical resection in week 13.

NOTE: **Patients with primary hepatic tumors do not receive radiotherapy in week 4.

Adjuvant chemotherapy with or without radiotherapy: Patients receive ifosfamide IV over 3 hours on days 1-3 in weeks 16 and 19 and doxorubicin hydrochloride IV over 24 hours on days 1 and 2 in weeks 16, 19***, and 22. Beginning in week 16, patients achieving gross total resection with positive microscopic margins undergo a total of 6 fractions of adjuvant radiotherapy. Patients achieving less than total gross resection undergo a total of 11 fractions of adjuvant radiotherapy. Patients achieving total gross resection with negative microscopic margins do not receive adjuvant radiotherapy.

NOTE: ***Patients who receive adjuvant radiotherapy in week 16 receive doxorubicin hydrochloride in week 25 instead of week 19.

GROUP 3 (high risk [metastatic, resected, incompletely resected, or unresected disease]):

Patients with low-grade, all-sites resected tumor with either negative or positive microscopic margins are assigned to receive treatment as in group 1 regimen A. Patients with high-grade, grossly resected primary tumor, and metastatic disease are assigned to receive treatment as in group 2 regimen C. Patients with unresected, high-grade metastatic tumor are assigned to receive treatment as in group 2 regimen D.

In all groups, treatment continues in the absence of disease progression. After completing study treatment, patients are followed periodically for at least 5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 588
• Est. completion date: March 31, 2022
• Est. primary completion date: September 5, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 29 Years

Eligibility

Inclusion Criteria:

• Newly diagnosed non-rhabdomyosarcoma soft tissue sarcoma (STS), confirmed by central pathology review via concurrent enrollment on protocol COG-D9902

• Metastatic or non metastatic disease

• Meets 1 of the following criteria:

• Intermediate (i.e., rarely metastasizing) or malignant STS, including any of the following:

• Adipocytic tumor, including liposarcoma of any of the following histology subtypes:

• Dedifferentiated

• Myxoid

• Round cell

• Pleomorphic type

• Mixed-type

• Not otherwise specified (NOS)

• Fibroblastic/myofibroblastic tumors, including any of the following:

• Solitary fibrous tumor

• Hemangiopericytoma

• Low-grade myofibroblastic sarcoma

• Myxoinflammatory fibroblastic sarcoma

• Adult fibrosarcoma*

• Myxofibrosarcoma

• Low-grade fibromyxoid sarcoma or hyalinizing spindle-cell tumor

• Sclerosing epithelioid fibrosarcoma

• So-called fibrohistiocytic tumors, including any of the following:

• Plexiform fibrohistiocytic tumor

• Giant cell tumor of soft tissues

• Pleomorphic malignant fibrous histiocytoma (MFH)/undifferentiated pleomorphic sarcoma

• Giant cell MFH/undifferentiated pleomorphic sarcoma with giant cells

• Inflammatory MFH/undifferentiated pleomorphic sarcoma with prominent inflammation

• Smooth muscle tumor (leiomyosarcoma)

• Pericytic [perivascular] tumor (malignant glomus tumor or glomangiosarcoma)

• Vascular tumor, including angiosarcoma

• Chondro-osseous tumors of any of the following types:

• Mesenchymal chondrosarcoma

• Extraskeletal osteosarcoma

• Tumors of uncertain differentiation, including any of the following:

• Angiomatoid fibrous histiocytoma

• Ossifying fibromyxoid tumor

• Myoepithelioma/parachordoma

• Synovial sarcoma

• Epithelioid sarcoma

• Alveolar soft-part sarcoma

• Clear cell sarcoma of soft tissue

• Extraskeletal myxoid chondrosarcoma ("chordoid type")

• Malignant mesenchymoma

• Neoplasms with perivascular epithelioid cell differentiation (PEComa)

• Clear cell myomelanocytic tumor

• Intimal sarcoma

• Malignant peripheral nerve sheath tumor

• Dermatofibrosarcoma protuberans meeting both of the following criteria:

• Non metastatic disease

• Tumor must be grossly resected prior to study enrollment

• Embryonal sarcoma of the liver

• Unclassified STS that is too undifferentiated to be placed in a specific pathologic category (undifferentiated STS or STS NOS)

• Gross resection of the primary tumor = 42 days prior to enrollment required except if any of the following circumstances apply:

• Non metastatic high-grade tumor > 5 cm in maximal diameter and gross or microscopic residual tumor is anticipated after resection

• Tumor of either high- or- low-grade that cannot be grossly excised without unacceptable morbidity

• High-grade tumor with metastases

• Patients with metastatic low-grade tumor whose disease is amenable to gross resection at all sites must undergo gross resection of all sites prior to study entry

• Patients with a tumor recurrence after a gross total resection are not eligible

• Tumors arising in bone are not eligible

• Patients with epithelioid sarcoma, clear cell sarcoma, or clinical or radiologic evidence of regional lymph node enlargement must undergo sentinel lymph node biopsies or lymph node sampling to confirm the status of regional lymph nodes* NOTE: *Except in cases where the study radiologist reviews the imaging and indicates that a biopsy is not needed to confirm that the patient has lymph node involvement.

• If lymph node biopsies are positive for tumor (or the lymph nodes are classified as positive by the study radiologist), formal lymph node dissection must be done at the time of definitive surgery(prior to study entry for patients assigned to study regimen C)

• Patients with metastatic disease must undergo a biopsy to confirm the presence of metastatic tumor if all metastases are < 1 cm in maximal diameter (except in cases where the study radiologist reviews the imaging and indicated that a biopsy is not needed to confirm that the patient has metastatic disease)

• Lansky performance status (PS) 50-100% (for patients = 16 years of age) OR Karnofsky PS 50-100% (for patients > 16 years of age)

• Life expectancy = 3 months

• Absolute neutrophil count = 1,000/mm³*

• Platelet count = 100,000/mm³*

• Creatinine clearance or radioisotope glomerular filtration rate = 70 mL/min (= 40 mL/min for infants < 1 year of age)* or serum creatinine based on age and/or gender as follows:

• 0.4 mg/dL (1 month to < 6 months of age)

• 0.5 mg/dL (6 months to < 1 year of age)

• 0.6 mg/dL (1 year to < 2 years of age)

• 0.8 mg/dL (2 years to < 6 years of age)

• 1.0 mg/dL (6 years to < 10 years of age)

• 1.2 mg/dL (10 years to < 13 years of age)

• 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 years to < 16 years of age)

• 1.7 mg/dL (male) or 1.4 mg/dL (female) (= 16 years of age)

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

• Bilirubin = 1.5 times upper limit of normal (ULN)*

• Shortening fraction = 27% by echocardiogram* OR ejection fraction = 50% by radionuclide angiogram*

• Not pregnant or nursing (patients undergoing radiotherapy and/or chemotherapy)

• No nursing for = 1 month after completion of study treatment in study regimens C or D

• Fertile patients must use effective contraception during and for = 1 month after completion of study treatment

• Negative pregnancy test

• No evidence of dyspnea at rest*

• No exercise intolerance*

• Resting pulse oximetry reading > 94% on room air (for patients with respiratory symptoms)*

• Prior treatment for cancer allowed provided the patient meet the prior therapy requirements

• No prior anthracycline (e.g., doxorubicin or daunorubicin) or ifosfamide chemotherapy for patients enrolled on arm C or arm D

• No prior radiotherapy to tumor-involved sites

Related Conditions & MeSH terms

• Adult Alveolar Soft-part Sarcoma
• Adult Angiosarcoma
• Adult Epithelioid Sarcoma
• Adult Extraskeletal Chondrosarcoma
• Adult Extraskeletal Osteosarcoma
• Adult Fibrosarcoma
• Adult Leiomyosarcoma
• Adult Liposarcoma
• Adult Malignant Fibrous Histiocytoma
• Adult Malignant Hemangiopericytoma
• Adult Malignant Mesenchymoma
• Adult Neurofibrosarcoma
• Adult Synovial Sarcoma
• Childhood Alveolar Soft-part Sarcoma
• Childhood Angiosarcoma
• Childhood Epithelioid Sarcoma
• Childhood Fibrosarcoma
• Childhood Leiomyosarcoma
• Childhood Liposarcoma
• Childhood Malignant Mesenchymoma
• Childhood Neurofibrosarcoma
• Childhood Synovial Sarcoma
• Chondrosarcoma
• Dermatofibrosarcoma
• Dermatofibrosarcoma Protuberans
• Fibrosarcoma
• Hemangiopericytoma
• Histiocytoma
• Histiocytoma, Malignant Fibrous
• Leiomyosarcoma
• Liposarcoma
• Metastatic Childhood Soft Tissue Sarcoma
• Nonmetastatic Childhood Soft Tissue Sarcoma
• Osteosarcoma
• Sarcoma
• Sarcoma, Alveolar Soft Part
• Sarcoma, Synovial
• Stage I Adult Soft Tissue Sarcoma
• Stage II Adult Soft Tissue Sarcoma
• Stage III Adult Soft Tissue Sarcoma
• Stage IV Adult Soft Tissue Sarcoma

Intervention

Drug:
• doxorubicin hydrochloride
Given IV

Other:
• clinical observation
Patients undergo observation

Procedure:
• therapeutic conventional surgery
Patients undergo surgery

Radiation:
• 3-dimensional conformal radiation therapy
Patients undergo radiotherapy

Drug:
• ifosfamide
Given IV

Locations

Country	Name	City	State
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Women's and Children's Hospital-Adelaide	North Adelaide	South Australia
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Australia	Sydney Children's Hospital	Randwick	New South Wales
Australia	The Children's Hospital at Westmead	Sydney	New South Wales
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	Chedoke-McMaster Hospitals	Hamilton	Ontario
Canada	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario
Canada	Hospital 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	Janeway Child Health Centre	Saint John's	Newfoundland and Labrador
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Centre Hospitalier Universitaire de Quebec	Ste-Foy	Quebec
Canada	Hospital for Sick Children	Toronto	Ontario
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
New Zealand	Starship Children's Hospital	Grafton	Auckland
Puerto Rico	San Jorge Children's Hospital	Santurce
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	Albany Medical Center	Albany	New York
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Texas Tech University Health Science Center-Amarillo	Amarillo	Texas
United States	C S Mott Children's Hospital	Ann Arbor	Michigan
United States	Children's Oncology Group	Arcadia	California
United States	Mission Hospitals Inc	Asheville	North Carolina
United States	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Dell Children's Medical Center of Central Texas	Austin	Texas
United States	Johns Hopkins University	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	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Saint Luke's Mountain States Tumor Institute	Boise	Idaho
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Brooklyn Hospital Center	Brooklyn	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Vermont	Burlington	Vermont
United States	University of North Carolina	Chapel Hill	North Carolina
United States	West Virginia University Charleston	Charleston	West Virginia
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Presbyterian Hospital	Charlotte	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	T C Thompson Children's Hospital	Chattanooga	Tennessee
United States	Childrens Memorial Hospital	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Rainbow Babies and Childrens Hospital	Cleveland	Ohio
United States	Palmetto Health Richland	Columbia	South Carolina
United States	University of Missouri-Columbia	Columbia	Missouri
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Driscoll Children's Hospital	Corpus Christi	Texas
United States	Medical City Dallas Hospital	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	The Children's Medical Center of Dayton	Dayton	Ohio
United States	Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center	Denver	Colorado
United States	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Wayne State University	Detroit	Michigan
United States	Southern California Permanente Medical Group	Downey	California
United States	City of Hope Medical Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Sanford Medical Center-Fargo	Fargo	North Dakota
United States	Hurley Medical Center	Flint	Michigan
United States	Broward Health Medical Center	Fort Lauderdale	Florida
United States	Lee Memorial Health System	Fort Myers	Florida
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	University of Florida	Gainesville	Florida
United States	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Saint Vincent Hospital	Green Bay	Wisconsin
United States	Greenville Cancer Treatment Center	Greenville	South Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Penn State Hershey Children's Hospital	Hershey	Pennsylvania
United States	Memorial Healthcare System - Joe DiMaggio Children's Hospital	Hollywood	Florida
United States	Tripler Army Medical Center	Honolulu	Hawaii
United States	University of Hawaii	Honolulu	Hawaii
United States	Baylor College of Medicine	Houston	Texas
United States	M D Anderson Cancer Center	Houston	Texas
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	Saint Vincent Hospital and Health Services	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Nemours Children's Clinic - Jacksonville	Jacksonville	Florida
United States	Kalamazoo Center for Medical Studies	Kalamazoo	Michigan
United States	The Childrens Mercy Hospital	Kansas City	Missouri
United States	East Tennessee Childrens Hospital	Knoxville	Tennessee
United States	Michigan State University - Breslin Cancer Center	Lansing	Michigan
United States	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Kentucky	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Miller Children's Hospital	Long Beach	California
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	David Geffen School of Medicine at UCLA	Los Angeles	California
United States	Kosair Children's Hospital	Louisville	Kentucky
United States	Covenant Children's Hospital	Lubbock	Texas
United States	Children's Hospital Central California	Madera	California
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Loyola University Medical Center	Maywood	Illinois
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Baptist Hospital of Miami	Miami	Florida
United States	Miami Children's Hospital	Miami	Florida
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota
United States	University of Minnesota Medical Center-Fairview	Minneapolis	Minnesota
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Saint Peter's University Hospital	New Brunswick	New Jersey
United States	UMDNJ - Robert Wood Johnson 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	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	New York University Langone Medical Center	New York	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Childrens Hospital-King's Daughters	Norfolk	Virginia
United States	Advocate Hope Children's Hospital	Oak Lawn	Illinois
United States	Children's Hospital and Research Center at Oakland	Oakland	California
United States	Kaiser Permanente-Oakland	Oakland	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Childrens Hospital of Orange County	Orange	California
United States	Florida Hospital	Orlando	Florida
United States	M D Anderson Cancer Center- Orlando	Orlando	Florida
United States	Nemours Childrens Clinic - Orlando	Orlando	Florida
United States	Lucile Packard Children's Hospital Stanford University	Palo Alto	California
United States	Advocate Lutheran General Hospital	Park Ridge	Illinois
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	Phoenix Childrens Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Legacy Emanuel Children's Hospital	Portland	Oregon
United States	Legacy Emanuel Hospital and Health Center	Portland	Oregon
United States	Oregon Health and Science University	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Saint John's Mercy Medical Center	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	All Children's Hospital	Saint Petersburg	Florida
United States	Primary Children's Medical Center	Salt Lake City	Utah
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	University of California San Francisco 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	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	Southern Illinois University	Springfield	Illinois
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Overlook Hospital	Summit	New Jersey
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Madigan Army Medical Center	Tacoma	Washington
United States	Mary Bridge Children's Hospital and Health Center	Tacoma	Washington
United States	Saint Joseph Children's Hospital of Tampa	Tampa	Florida
United States	Scott and White Memorial Hospital	Temple	Texas
United States	Mercy Children's Hospital	Toledo	Ohio
United States	The Toledo Hospital/Toledo Children's Hospital	Toledo	Ohio
United States	University of Arizona Health Sciences Center	Tucson	Arizona
United States	New York Medical College	Valhalla	New York
United States	Children's National Medical Center	Washington	District of Columbia
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	University of Massachusetts Medical School	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada,  New Zealand,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Probability for Event Free Survival.	Probability of no relapse, secondary malignancy or death after 5 years since enrollment.	5 years
Secondary	Toxicity Rate	Percentage of Arm D patients experiencing grade 4+ adverse events.	13 weeks
Secondary	Complete or Partial Response Rate	Tumor response by imaging. Complete Response (CR): Complete disappearance of the tumor. Partial Response (PR): At least 64% decrease in volume compared to the measurement obtained at study enrollment. Overall Response (OR)=CR+PR.	13 weeks
Secondary	Percent Tumor Necrosis	Percent tumor necrosis by pathology review.	13 weeks
Secondary	Event Free Survival Probability Disease Extent	Probability of no relapse, secondary malignancy or death after 5 years since enrollment.	5 years
Secondary	Event Free Survival Probability Histologic Grade	Probability of no relapse, secondary malignancy or death after 5 years since enrollment	5 years
Secondary	Overall Survival Probability Disease Extent	Probability of survival after 5 years since enrollment.	5 years
Secondary	Overall Survival Probability Extent of Resection of the Primary Tumor	Probability of survival after 5 years since enrollment.	5 years
Secondary	Incidence of Distant Metastasis	Percent of patients who had distant metastasis.	Up to 10 years
Secondary	Genetic and Gene Expression Profiles	The tumors from patients registered on D9902 will be analyzed for genetic and gene expression profiles. The study will prospectively evaluate each tumor and confirm newly defined sarcoma diagnostic criteria based on cancer signatures in NRSTS.	At diagnosis
Secondary	Degree of Agreement in Histologic Grade Determined by the Enrolling Institution Versus by Central Pathology Reviewers	Histologic grades were determined by the central pathology reviewers and institutional pathologists based on published standards. A higher grade is associated with a more severe disease.	At Diagnosis
Secondary	Degree of Agreement in Histologic Grade Between Pediatric Oncology Group (POG) and Fédération Nationale Des Centres de Lutte Contre le Cancer (FNCLCC) Pathologic Grading Systems	POG and FNCLCC grades were determined by pathologists based on published standards. A higher grade is associated with a more severe disease.	At diagnosis

External Links

•   Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive