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

April 1, 2022 updated by: Children's Oncology Group

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

588

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

  • Australia
    • New South Wales
      • Randwick, New South Wales, Australia, 2031
        • Sydney Children's Hospital
      • Sydney, New South Wales, Australia, 2145
        • The Children's Hospital at Westmead
    • Queensland
      • Herston, Queensland, Australia, 4029
        • Royal Brisbane and Women's Hospital
    • South Australia
      • North Adelaide, South Australia, Australia, 5006
        • Women's and Children's Hospital-Adelaide
    • Victoria
      • Parkville, Victoria, Australia, 3052
        • Royal Children's Hospital
    • Western Australia
      • Perth, Western Australia, Australia, 6008
        • Princess Margaret Hospital for Children
  • Canada
    • 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, B3J 3G9
        • IWK Health Centre
    • Ontario
      • Hamilton, Ontario, Canada, L8S 4L8
        • Chedoke-McMaster Hospitals
      • Kingston, Ontario, Canada, K7L 5P9
        • Cancer Centre of Southeastern Ontario At Kingston General 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
        • Hospital Sainte-Justine
      • Ste-Foy, Quebec, Canada, G1V 4G2
        • Centre Hospitalier Universitaire de Quebec
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7N 4H4
        • Saskatoon Cancer Centre
  • New Zealand
    • Auckland
      • Grafton, Auckland, New Zealand, 1145
        • Starship Children's Hospital
  • Puerto Rico
      • Santurce, Puerto Rico, 00912
        • San Jorge Children's Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham
    • Arizona
      • Phoenix, Arizona, United States, 85016
        • Phoenix Childrens Hospital
      • Tucson, Arizona, United States, 85724
        • University of Arizona Health Sciences Center
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences
    • California
      • Arcadia, California, United States, 91006-3776
        • Children's Oncology Group
      • Downey, California, United States, 90242
        • Southern California Permanente Medical Group
      • Duarte, California, United States, 91010
        • City of Hope Medical Center
      • Loma Linda, California, United States, 92354
        • Loma Linda University Medical Center
      • Long Beach, California, United States, 90806
        • Miller Children's Hospital
      • Los Angeles, California, United States, 90048
        • Cedars-Sinai Medical Center
      • Los Angeles, California, United States, 90027
        • Children's Hospital Los Angeles
      • Los Angeles, California, United States, 90095
        • David Geffen School of Medicine at UCLA
      • Madera, California, United States, 93636-8762
        • Children's Hospital Central California
      • Oakland, California, United States, 94611
        • Kaiser Permanente-Oakland
      • Oakland, California, United States, 94609-1809
        • Children's Hospital and Research Center at Oakland
      • Orange, California, United States, 92868-3874
        • Childrens Hospital of Orange County
      • Palo Alto, California, United States, 94304
        • Lucile Packard Children's Hospital Stanford University
      • San Diego, California, United States, 92123
        • Rady Children's Hospital - San Diego
      • San Francisco, California, United States, 94143
        • University of California San Francisco Medical Center-Parnassus
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado
      • Denver, Colorado, United States, 80218
        • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
    • Connecticut
      • Hartford, Connecticut, United States, 06106
        • Connecticut Children's Medical Center
      • New Haven, Connecticut, United States, 06520-8032
        • 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
    • Florida
      • Fort Lauderdale, Florida, United States, 33316
        • Broward Health Medical Center
      • Fort Myers, Florida, United States, 33901
        • Lee Memorial Health System
      • Gainesville, Florida, United States, 32610
        • University of Florida
      • Hollywood, Florida, United States, 33021
        • Memorial Healthcare System - Joe DiMaggio Children's Hospital
      • Jacksonville, Florida, United States, 32207-8426
        • Nemours Children's Clinic - Jacksonville
      • Miami, Florida, United States, 33136
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
      • Miami, Florida, United States, 33176
        • Baptist Hospital of Miami
      • Miami, Florida, United States, 33155
        • Miami Children's Hospital
      • Orlando, Florida, United States, 32803
        • Florida Hospital
      • Orlando, Florida, United States, 32806
        • M D Anderson Cancer Center- Orlando
      • Orlando, Florida, United States, 32806
        • Nemours Childrens Clinic - Orlando
      • Pensacola, Florida, United States, 32504
        • Nemours Children's Clinic - Pensacola
      • Saint Petersburg, Florida, United States, 33701
        • All Children's Hospital
      • Tampa, Florida, United States, 33607
        • Saint Joseph Children's Hospital of Tampa
      • West Palm Beach, Florida, United States, 33407
        • Saint Mary's Hospital
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Children's Healthcare of Atlanta - Egleston
      • Savannah, Georgia, United States, 31403
        • Memorial Health University Medical Center
    • Hawaii
      • Honolulu, Hawaii, United States, 96859
        • Tripler Army Medical Center
      • Honolulu, Hawaii, United States, 96813
        • University of Hawaii
    • Idaho
      • Boise, Idaho, United States, 83712
        • Saint Luke's Mountain States Tumor Institute
    • Illinois
      • Chicago, Illinois, United States, 60637-1470
        • University of Chicago Comprehensive Cancer Center
      • Chicago, Illinois, United States, 60612
        • University of Illinois
      • Chicago, Illinois, United States, 60614
        • Childrens Memorial Hospital
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center
      • Oak Lawn, Illinois, United States, 60453
        • Advocate Hope Children's Hospital
      • Park Ridge, Illinois, United States, 60068
        • Advocate Lutheran General Hospital
      • Peoria, Illinois, United States, 61602
        • Saint Jude Midwest Affiliate
      • Springfield, Illinois, United States, 62702
        • Southern Illinois University
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Riley Hospital for Children
      • Indianapolis, Indiana, United States, 46260
        • Saint Vincent Hospital and Health Services
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinics
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky
      • Louisville, Kentucky, United States, 40202
        • Kosair Children's Hospital
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane University Health Sciences Center
    • 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, 21215
        • Sinai Hospital of Baltimore
      • Baltimore, Maryland, United States, 21287-8936
        • Johns Hopkins University
      • Baltimore, Maryland, United States, 21201-1595
        • University of Maryland Greenebaum Cancer Center
      • Bethesda, Maryland, United States, 20889-5600
        • Walter Reed National Military Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Cancer Center
      • Worcester, Massachusetts, United States, 01655
        • University of Massachusetts Medical School
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • C S Mott Children's Hospital
      • Detroit, Michigan, United States, 48236
        • Saint John Hospital and Medical Center
      • Detroit, Michigan, United States, 48202
        • Wayne State University
      • Flint, Michigan, United States, 48502
        • Hurley Medical Center
      • Grand Rapids, Michigan, United States, 49503
        • Helen DeVos Children's Hospital at Spectrum Health
      • Kalamazoo, Michigan, United States, 49008
        • Kalamazoo Center for Medical Studies
      • Lansing, Michigan, United States, 48910
        • Michigan State University - Breslin Cancer Center
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Children's Hospitals and Clinics of Minnesota - Minneapolis
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Medical Center-Fairview
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • Missouri
      • Columbia, Missouri, United States, 65212
        • University of Missouri-Columbia
      • Kansas City, Missouri, United States, 64108
        • The Childrens Mercy Hospital
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
      • Saint Louis, Missouri, United States, 63141
        • Saint John's Mercy Medical Center
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
    • Nevada
      • Las Vegas, Nevada, United States, 89106
        • Nevada Cancer Research Foundation CCOP
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
      • New Brunswick, New Jersey, United States, 08901
        • Saint Peter's University Hospital
      • New Brunswick, New Jersey, United States, 08903
        • UMDNJ - 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
      • Summit, New Jersey, United States, 07902
        • Overlook Hospital
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • University of New Mexico Cancer Center
    • New York
      • Albany, New York, United States, 12208
        • Albany Medical Center
      • Bronx, New York, United States, 10467-2490
        • Montefiore Medical Center
      • Brooklyn, New York, United States, 11201
        • Brooklyn Hospital Center
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • 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, 10032
        • Columbia University Medical Center
      • New York, New York, United States, 10029
        • Mount Sinai Medical Center
      • New York, New York, United States, 10016
        • New York University Langone Medical Center
      • 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 Hospitals Inc
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Carolinas Medical Center
      • Charlotte, North Carolina, United States, 28204
        • Presbyterian Hospital
      • 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 Medical Center-Fargo
    • Ohio
      • Akron, Ohio, United States, 44308
        • Children's Hospital Medical Center of Akron
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
      • 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
        • The Children's Medical Center of Dayton
      • Toledo, Ohio, United States, 43606
        • The Toledo Hospital/Toledo Children's Hospital
      • Toledo, Ohio, United States, 43608
        • Mercy Children's Hospital
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
      • Portland, Oregon, United States, 97227
        • Legacy Emanuel Children's Hospital
      • Portland, Oregon, United States, 97227
        • Legacy Emanuel Hospital and Health Center
    • Pennsylvania
      • Bethlehem, Pennsylvania, United States, 18017
        • Lehigh Valley Hospital - Muhlenberg
      • Danville, Pennsylvania, United States, 17822-2001
        • Geisinger Medical Center
      • Hershey, Pennsylvania, United States, 17033
        • Penn State Hershey Children's Hospital
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
      • 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
      • Columbia, South Carolina, United States, 29203
        • Palmetto Health Richland
      • Greenville, South Carolina, United States, 29605
        • Greenville Cancer Treatment 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
      • Knoxville, Tennessee, United States, 37916
        • East Tennessee Childrens Hospital
      • Memphis, Tennessee, United States, 38105
        • St. Jude Children's Research Hospital
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt-Ingram Cancer Center
    • Texas
      • Amarillo, Texas, United States, 79106
        • Texas Tech University Health Science Center-Amarillo
      • Austin, Texas, United States, 78723
        • Dell Children's Medical Center of Central Texas
      • Corpus Christi, Texas, United States, 78411
        • Driscoll Children's Hospital
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center
      • Dallas, Texas, United States, 75230
        • Medical City Dallas Hospital
      • Fort Sam Houston, Texas, United States, 78234
        • Brooke Army Medical Center
      • 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
      • Lubbock, Texas, United States, 79410
        • Covenant Children's Hospital
      • San Antonio, Texas, United States, 78229
        • Methodist Children's Hospital of South Texas
      • San Antonio, Texas, United States, 78229-3900
        • University of Texas Health Science Center at San Antonio
      • Temple, Texas, United States, 76508
        • Scott and White Memorial Hospital
    • Utah
      • Salt Lake City, Utah, United States, 84113
        • Primary Children's Medical Center
    • Vermont
      • Burlington, Vermont, United States, 05401
        • University of Vermont
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia
      • Falls Church, Virginia, United States, 22042
        • Inova Fairfax Hospital
      • Norfolk, Virginia, United States, 23507
        • Childrens Hospital-King's Daughters
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University
    • Washington
      • 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, 98431
        • Madigan Army Medical Center
    • West Virginia
      • Charleston, West Virginia, United States, 25304
        • West Virginia University Charleston
    • Wisconsin
      • Green Bay, Wisconsin, United States, 54301
        • Saint Vincent Hospital
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Hospital and Clinics
      • Marshfield, Wisconsin, United States, 54449
        • Marshfield Clinic
      • Milwaukee, Wisconsin, United States, 53226
        • Midwest Children's Cancer Center

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 27 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A: No adjuvant treatment
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 arm A: (observation only).
Other: clinical observation
Patients undergo observation
Other Names:
  • observation
Procedure: therapeutic conventional surgery
Patients undergo surgery
Experimental: Arm B: Low risk; adjuvant radiotherapy
Patients with high-grade tumor ≤ 5 cm (in maximum diameter) with positive microscopic margins are assigned to arm B: (adjuvant radiotherapy). Beginning between 6-42 days after surgical resection, patients undergo a total of 31 fractions of adjuvant radiotherapy.
Radiation: 3-dimensional conformal radiation therapy
Patients undergo radiotherapy
Other Names:
  • 3D-CRT
  • 3D conformal radiation therapy
Other: clinical observation
Patients undergo observation
Other Names:
  • observation
Procedure: therapeutic conventional surgery
Patients undergo surgery
Experimental: Arm C: Intermediate & High risk; adjuvant chemoradiotherapy
High risk [metastatic, resected, incompletely resected, or unresected disease] patients with high-grade, grossly resected primary tumor, with metastases are assigned to receive arm C: (adjuvant chemoradiotherapy). Patients receive ifosfamide IV; doxorubicin hydrochloride IV; beginning in week 4, patients also undergo a total of 31 fractions of radiotherapy.
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • Adriamycin PFS
  • Adriamycin RDF
  • ADR
  • Adria
Radiation: 3-dimensional conformal radiation therapy
Patients undergo radiotherapy
Other Names:
  • 3D-CRT
  • 3D conformal radiation therapy
Drug: ifosfamide
Given IV
Other Names:
  • Cyfos
  • Holoxan
  • IFX
  • IFF
  • IPP
Other: clinical observation
Patients undergo observation
Other Names:
  • observation
Experimental: Arm D: Intermediate & High Risk; Neoadjuvant chemoradiotherapy
High risk [metastatic, resected, incompletely resected, or unresected disease] patients with unresected, high-grade metastatic tumor are assigned to receive treatment as in arm D: (neoadjuvant chemoradiotherapy, surgery, and adjuvant chemotherapy with or without radiotherapy): Patients receive ifosfamide IV; doxorubicin hydrochloride IV. Beginning in week 4, patients also undergo a total of 31 fractions of radiotherapy. Patients undergo surgical resection in week 13.
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • Adriamycin PFS
  • Adriamycin RDF
  • ADR
  • Adria
Radiation: 3-dimensional conformal radiation therapy
Patients undergo radiotherapy
Other Names:
  • 3D-CRT
  • 3D conformal radiation therapy
Drug: ifosfamide
Given IV
Other Names:
  • Cyfos
  • Holoxan
  • IFX
  • IFF
  • IPP
Other: clinical observation
Patients undergo observation
Other Names:
  • observation
Procedure: therapeutic conventional surgery
Patients undergo surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Probability for Event Free Survival.
Time Frame: 5 years
Probability of no relapse, secondary malignancy or death after 5 years since enrollment.
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Toxicity Rate
Time Frame: 13 weeks
Percentage of Arm D patients experiencing grade 4+ adverse events.
13 weeks
Complete or Partial Response Rate
Time Frame: 13 weeks
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
Percent Tumor Necrosis
Time Frame: 13 weeks
Percent tumor necrosis by pathology review.
13 weeks
Event Free Survival Probability Disease Extent
Time Frame: 5 years
Probability of no relapse, secondary malignancy or death after 5 years since enrollment.
5 years
Event Free Survival Probability Histologic Grade
Time Frame: 5 years
Probability of no relapse, secondary malignancy or death after 5 years since enrollment
5 years
Overall Survival Probability Disease Extent
Time Frame: 5 years
Probability of survival after 5 years since enrollment.
5 years
Overall Survival Probability Extent of Resection of the Primary Tumor
Time Frame: 5 years
Probability of survival after 5 years since enrollment.
5 years
Incidence of Distant Metastasis
Time Frame: Up to 10 years
Percent of patients who had distant metastasis.
Up to 10 years
Genetic and Gene Expression Profiles
Time Frame: At diagnosis
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
Degree of Agreement in Histologic Grade Determined by the Enrolling Institution Versus by Central Pathology Reviewers
Time Frame: At Diagnosis
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
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
Time Frame: At diagnosis
POG and FNCLCC grades were determined by pathologists based on published standards. A higher grade is associated with a more severe disease.
At diagnosis

Collaborators and Investigators

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

Sponsor

Children's Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Sheri Spunt, MD, Children's Oncology Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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)

February 5, 2007

Primary Completion (Actual)

September 5, 2014

Study Completion (Actual)

March 31, 2022

Study Registration Dates

First Submitted

June 28, 2006

First Submitted That Met QC Criteria

June 28, 2006

First Posted (Estimate)

June 29, 2006

Study Record Updates

Last Update Posted (Actual)

April 28, 2022

Last Update Submitted That Met QC Criteria

April 1, 2022

Last Verified

June 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ARST0332
  • U10CA098543 (U.S. NIH Grant/Contract)
  • NCI-2009-00426 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • COG-ARST0332 (Other Identifier: Children's Oncology Group)
  • CDR0000483702 (Other Identifier: Clinical Trials.gov)

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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