AzTrials
AzTrials

Adult Alveolar Soft-part SarcomaPhase 3NCT00346164

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

A Phase 3 study testing doxorubicin hydrochloride, clinical observation and therapeutic conventional surgery in people with Adult Alveolar Soft-part Sarcoma and Adult Angiosarcoma, run by Children's Oncology Group at 187 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages Up to 29 years
What is being tested?
doxorubicin hydrochloride, clinical observation and therapeutic conventional surgery
Could I receive a placebo?
No, everyone receives an active treatment
How many people
588 participants
Where
187 sitesin 5 countries
Study dates
5 Feb 2007to 31 Mar 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 29 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
Show all 87Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

187 sites in 5 countries.

187 sites in 5 countries

United States165 sites

  • Children's Hospital Medical Center of Akron

    Akron, Ohio, 44308

  • Albany Medical Center

    Albany, New York, 12208

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87106

  • Texas Tech University Health Science Center-Amarillo

    Amarillo, Texas, 79106

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • Children's Oncology Group

    Arcadia, California, 91006-3776

  • Mission Hospitals Inc

    Asheville, North Carolina, 28801

  • Children's Healthcare of Atlanta - Egleston

    Atlanta, Georgia, 30322

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Dell Children's Medical Center of Central Texas

    Austin, Texas, 78723

  • University of Maryland Greenebaum Cancer Center

    Baltimore, Maryland, 21201-1595

  • Sinai Hospital of Baltimore

    Baltimore, Maryland, 21215

  • Johns Hopkins University

    Baltimore, Maryland, 21287-8936

  • Eastern Maine Medical Center

    Bangor, Maine, 04401

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889-5600

  • Lehigh Valley Hospital - Muhlenberg

    Bethlehem, Pennsylvania, 18017

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Saint Luke's Mountain States Tumor Institute

    Boise, Idaho, 83712

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Brooklyn Hospital Center

    Brooklyn, New York, 11201

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • University of Vermont

    Burlington, Vermont, 05401

  • University of North Carolina

    Chapel Hill, North Carolina, 27599

  • West Virginia University Charleston

    Charleston, West Virginia, 25304

  • Carolinas Medical Center

    Charlotte, North Carolina, 28203

  • Presbyterian Hospital

    Charlotte, North Carolina, 28204

  • University of Virginia

    Charlottesville, Virginia, 22908

  • T C Thompson Children's Hospital

    Chattanooga, Tennessee, 37403

  • University of Illinois

    Chicago, Illinois, 60612

  • Childrens Memorial Hospital

    Chicago, Illinois, 60614

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637-1470

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Rainbow Babies and Childrens Hospital

    Cleveland, Ohio, 44106

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • University of Missouri-Columbia

    Columbia, Missouri, 65212

  • Palmetto Health Richland

    Columbia, South Carolina, 29203

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • Driscoll Children's Hospital

    Corpus Christi, Texas, 78411

  • Medical City Dallas Hospital

    Dallas, Texas, 75230

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822-2001

  • The Children's Medical Center of Dayton

    Dayton, Ohio, 45404

  • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

    Denver, Colorado, 80218

  • Wayne State University

    Detroit, Michigan, 48202

  • Saint John Hospital and Medical Center

    Detroit, Michigan, 48236

  • Southern California Permanente Medical Group

    Downey, California, 90242

  • City of Hope Medical Center

    Duarte, California, 91010

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Inova Fairfax Hospital

    Falls Church, Virginia, 22042

  • Sanford Medical Center-Fargo

    Fargo, North Dakota, 58122

  • Hurley Medical Center

    Flint, Michigan, 48502

  • Broward Health Medical Center

    Fort Lauderdale, Florida, 33316

  • Lee Memorial Health System

    Fort Myers, Florida, 33901

  • Brooke Army Medical Center

    Fort Sam Houston, Texas, 78234

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

  • University of Florida

    Gainesville, Florida, 32610

  • Helen DeVos Children's Hospital at Spectrum Health

    Grand Rapids, Michigan, 49503

  • Saint Vincent Hospital

    Green Bay, Wisconsin, 54301

  • Greenville Cancer Treatment Center

    Greenville, South Carolina, 29605

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Connecticut Children's Medical Center

    Hartford, Connecticut, 06106

  • Penn State Hershey Children's Hospital

    Hershey, Pennsylvania, 17033

  • Memorial Healthcare System - Joe DiMaggio Children's Hospital

    Hollywood, Florida, 33021

  • University of Hawaii

    Honolulu, Hawaii, 96813

  • Tripler Army Medical Center

    Honolulu, Hawaii, 96859

  • Baylor College of Medicine

    Houston, Texas, 77030

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • Saint Vincent Hospital and Health Services

    Indianapolis, Indiana, 46260

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Nemours Children's Clinic - Jacksonville

    Jacksonville, Florida, 32207-8426

  • Kalamazoo Center for Medical Studies

    Kalamazoo, Michigan, 49008

  • The Childrens Mercy Hospital

    Kansas City, Missouri, 64108

  • East Tennessee Childrens Hospital

    Knoxville, Tennessee, 37916

  • Michigan State University - Breslin Cancer Center

    Lansing, Michigan, 48910

  • Nevada Cancer Research Foundation CCOP

    Las Vegas, Nevada, 89106

  • Dartmouth Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • University of Kentucky

    Lexington, Kentucky, 40536

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • Loma Linda University Medical Center

    Loma Linda, California, 92354

  • Miller Children's Hospital

    Long Beach, California, 90806

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • David Geffen School of Medicine at UCLA

    Los Angeles, California, 90095

  • Kosair Children's Hospital

    Louisville, Kentucky, 40202

  • Covenant Children's Hospital

    Lubbock, Texas, 79410

  • Children's Hospital Central California

    Madera, California, 93636-8762

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Marshfield Clinic

    Marshfield, Wisconsin, 54449

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • Miami Children's Hospital

    Miami, Florida, 33155

  • Baptist Hospital of Miami

    Miami, Florida, 33176

  • Midwest Children's Cancer Center

    Milwaukee, Wisconsin, 53226

  • Children's Hospitals and Clinics of Minnesota - Minneapolis

    Minneapolis, Minnesota, 55404

  • University of Minnesota Medical Center-Fairview

    Minneapolis, Minnesota, 55455

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Saint Peter's University Hospital

    New Brunswick, New Jersey, 08901

  • UMDNJ - Robert Wood Johnson University Hospital

    New Brunswick, New Jersey, 08903

  • Yale University

    New Haven, Connecticut, 06520-8032

  • The Steven and Alexandra Cohen Children's Medical Center of New York

    New Hyde Park, New York, 11040

  • Tulane University Health Sciences Center

    New Orleans, Louisiana, 70112

  • New York University Langone Medical Center

    New York, New York, 10016

  • Mount Sinai Medical Center

    New York, New York, 10029

  • Columbia University Medical Center

    New York, New York, 10032

  • Newark Beth Israel Medical Center

    Newark, New Jersey, 07112

  • Childrens Hospital-King's Daughters

    Norfolk, Virginia, 23507

  • Advocate Hope Children's Hospital

    Oak Lawn, Illinois, 60453

  • Children's Hospital and Research Center at Oakland

    Oakland, California, 94609-1809

  • Kaiser Permanente-Oakland

    Oakland, California, 94611

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Childrens Hospital of Orange County

    Orange, California, 92868-3874

  • Florida Hospital

    Orlando, Florida, 32803

  • M D Anderson Cancer Center- Orlando

    Orlando, Florida, 32806

  • Nemours Childrens Clinic - Orlando

    Orlando, Florida, 32806

  • Lucile Packard Children's Hospital Stanford University

    Palo Alto, California, 94304

  • Advocate Lutheran General Hospital

    Park Ridge, Illinois, 60068

  • Saint Joseph's Regional Medical Center

    Paterson, New Jersey, 07503

  • Nemours Children's Clinic - Pensacola

    Pensacola, Florida, 32504

  • Saint Jude Midwest Affiliate

    Peoria, Illinois, 61602

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Phoenix Childrens Hospital

    Phoenix, Arizona, 85016

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • Legacy Emanuel Children's Hospital

    Portland, Oregon, 97227

  • Legacy Emanuel Hospital and Health Center

    Portland, Oregon, 97227

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • Virginia Commonwealth University

    Richmond, Virginia, 23298

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of Rochester

    Rochester, New York, 14642

  • Primary Children's Medical Center

    Salt Lake City, Utah, 84113

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229-3900

  • Methodist Children's Hospital of South Texas

    San Antonio, Texas, 78229

  • Rady Children's Hospital - San Diego

    San Diego, California, 92123

  • University of California San Francisco Medical Center-Parnassus

    San Francisco, California, 94143

  • Memorial Health University Medical Center

    Savannah, Georgia, 31403

  • Maine Children's Cancer Program

    Scarborough, Maine, 04074

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Sanford USD Medical Center - Sioux Falls

    Sioux Falls, South Dakota, 57117-5134

  • Providence Sacred Heart Medical Center and Children's Hospital

    Spokane, Washington, 99204

  • Southern Illinois University

    Springfield, Illinois, 62702

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Saint John's Mercy Medical Center

    St Louis, Missouri, 63141

  • All Children's Hospital

    St. Petersburg, Florida, 33701

  • Stony Brook University Medical Center

    Stony Brook, New York, 11794

  • Overlook Hospital

    Summit, New Jersey, 07902

  • State University of New York Upstate Medical University

    Syracuse, New York, 13210

  • Mary Bridge Children's Hospital and Health Center

    Tacoma, Washington, 98405

  • Madigan Army Medical Center

    Tacoma, Washington, 98431

  • Saint Joseph Children's Hospital of Tampa

    Tampa, Florida, 33607

  • Scott and White Memorial Hospital

    Temple, Texas, 76508

  • Montefiore Medical Center

    The Bronx, New York, 10467-2490

  • The Toledo Hospital/Toledo Children's Hospital

    Toledo, Ohio, 43606

  • Mercy Children's Hospital

    Toledo, Ohio, 43608

  • University of Arizona Health Sciences Center

    Tucson, Arizona, 85724

  • New York Medical College

    Valhalla, New York, 10595

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

  • Saint Mary's Hospital

    West Palm Beach, Florida, 33407

  • Alfred I duPont Hospital for Children

    Wilmington, Delaware, 19803

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

  • University of Massachusetts Medical School

    Worcester, Massachusetts, 01655

Other trials in United States

Canada14 sites

  • Alberta Children's Hospital

    Calgary, Alberta, T3B 6A8

  • University of Alberta Hospital

    Edmonton, Alberta, T6G 2B7

  • IWK Health Centre

    Halifax, Nova Scotia, B3J 3G9

  • Chedoke-McMaster Hospitals

    Hamilton, Ontario, L8S 4L8

  • Cancer Centre of Southeastern Ontario at Kingston General Hospital

    Kingston, Ontario, K7L 5P9

  • The Montreal Children's Hospital of the MUHC

    Montreal, Quebec, H3H 1P3

  • Hospital Sainte-Justine

    Montreal, Quebec, H3T 1C5

  • Children's Hospital of Eastern Ontario

    Ottawa, Ontario, K1H 8L1

  • Saskatoon Cancer Centre

    Saskatoon, Saskatchewan, S7N 4H4

  • Janeway Child Health Centre

    St. John's, Newfoundland and Labrador, A1B 3V6

  • Centre Hospitalier Universitaire de Quebec

    Ste-Foy, Quebec, G1V 4G2

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

  • British Columbia Children's Hospital

    Vancouver, British Columbia, V6H 3V4

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

Australia6 sites

  • Royal Brisbane and Women's Hospital

    Herston, Queensland, 4029

  • Women's and Children's Hospital-Adelaide

    North Adelaide, South Australia, 5006

  • Royal Children's Hospital

    Parkville, Victoria, 3052

  • Princess Margaret Hospital for Children

    Perth, Western Australia, 6008

  • Sydney Children's Hospital

    Randwick, New South Wales, 2031

  • The Children's Hospital at Westmead

    Sydney, New South Wales, 2145

Other trials in Australia

New Zealand1 site

  • Starship Children's Hospital

    Grafton, Auckland, 1145

Other trials in New Zealand

Puerto Rico1 site

  • San Jorge Children's Hospital

    Santurce, 00912

Other trials in Puerto Rico

About this study

Official title: 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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

  1. 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.

Being tested
doxorubicin hydrochloride, clinical observation, therapeutic conventional surgery, 3-dimensional conformal radiation therapy, ifosfamide
Medical subject headings
Sarcoma, Alveolar Soft Part, Hemangiosarcoma, Sarcoma, Chondrosarcoma, Extraskeletal Myxoid, Fibrosarcoma, Leiomyosarcoma, Liposarcoma, Histiocytoma, Malignant Fibrous

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • doxorubicin hydrochlorideDrug

    Also called ADM, ADR, Adria, Adriamycin PFS

    Given IV

  • clinical observationOther

    Also called observation

    Patients undergo observation

  • therapeutic conventional surgeryProcedure or surgery

    Patients undergo surgery

  • 3-dimensional conformal radiation therapyRadiation

    Also called 3D conformal radiation therapy, 3D-CRT

    Patients undergo radiotherapy

  • ifosfamideDrug

    Also called Cyfos, Holoxan, IFF, IFX

    Given IV

Study groups in NCT00346164
Study groupRoleWhat they receive
Arm A: No adjuvant treatmentExperimentalPatients 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).
Receives: Other: clinical observation; Procedure: therapeutic conventional surgery
Arm B: Low risk; adjuvant radiotherapyExperimentalPatients 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.
Receives: Other: clinical observation; Procedure: therapeutic conventional surgery; Radiation: 3-dimensional conformal radiation therapy
Arm C: Intermediate & High risk; adjuvant chemoradiotherapyExperimentalHigh 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.
Receives: Drug: doxorubicin hydrochloride; Other: clinical observation; Radiation: 3-dimensional conformal radiation therapy; Drug: ifosfamide
Arm D: Intermediate & High Risk; Neoadjuvant chemoradiotherapyExperimentalHigh 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.
Receives: Drug: doxorubicin hydrochloride; Other: clinical observation; Procedure: therapeutic conventional surgery; Radiation: 3-dimensional conformal radiation therapy; Drug: ifosfamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Probability for Event Free Survival.

    Probability of no relapse, secondary malignancy or death after 5 years since enrollment.

    Measured: 5 years

Secondary outcomes (11)

  1. Toxicity Rate

    Percentage of Arm D patients experiencing grade 4+ adverse events.

    Measured: 13 weeks

  2. 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.

    Measured: 13 weeks

  3. Percent Tumor Necrosis

    Percent tumor necrosis by pathology review.

    Measured: 13 weeks

  4. Event Free Survival Probability Disease Extent

    Probability of no relapse, secondary malignancy or death after 5 years since enrollment.

    Measured: 5 years

  5. Event Free Survival Probability Histologic Grade

    Probability of no relapse, secondary malignancy or death after 5 years since enrollment

    Measured: 5 years

  6. Overall Survival Probability Disease Extent

    Probability of survival after 5 years since enrollment.

    Measured: 5 years

  7. Overall Survival Probability Extent of Resection of the Primary Tumor

    Probability of survival after 5 years since enrollment.

    Measured: 5 years

  8. Incidence of Distant Metastasis

    Percent of patients who had distant metastasis.

    Measured: Up to 10 years

  9. 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.

    Measured: At diagnosis

  10. 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.

    Measured: At Diagnosis

  11. 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.

    Measured: At diagnosis

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jun 2006 (estimated)
  2. Study start5 Feb 2007
  3. Primary completion5 Sep 2014
  4. Study completion31 Mar 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
588 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00346164
Sponsor's protocol ID
ARST0332
Other IDs
NCI-2009-00426, COG-ARST0332, CDR0000483702, U10CA098543
Status last verified
Jun 2021
First submitted
28 Jun 2006
Last updated
28 Apr 2022
Data monitoring committee
Yes

Publications

  • Hiniker SM, Dixon AH, Xue W, Gao Z, Million L, Black J, McCarville MB, Barkauskas DA, Meyer W, Weiss AR, Rodeberg D, Spunt SL, Randall RL. Surgical Margin and Risk of Local Recurrence in Children and Young Adults With Nonrhabdomyosarcoma Soft Tissue Sarcoma: A Nonrandomized Clinical Trial. JAMA Surg. 2026 Oct 28:e265032. doi: 10.1001/jamasurg.2026.5032. Online ahead of print.

    PubMed 42949735

  • Crane JN, Xue W, Qumseya A, Barkauskas DA, Chau K, Tan SY, Hiniker S, Dasgupta R, Venkatramani R, Spunt SL, Weiss AR, Laetsch TW. Malignant peripheral nerve sheath tumors: a report from Children's Oncology Group study ARST0332. J Natl Cancer Inst. 2026 May 1;118(5):829-838. doi: 10.1093/jnci/djaf359.

    PubMed 41386267

  • Douglass DP, Coffin CM, Randall RL, Yang Y, Barkauskas DA, Million L, McCarville MB, Pappo AS, Weiss AR, Spunt SL. Clinical features and outcomes of young patients with low-grade non-rhabdomyosarcoma soft tissue sarcomas treated with a risk-based strategy: A report from Children's Oncology Group study ARST0332. Pediatr Blood Cancer. 2024 Aug;71(8):e31062. doi: 10.1002/pbc.31062. Epub 2024 May 16.

    PubMed 38757485

  • Alvarez E, He J, Spunt SL, Hayes-Jordan A, Kao SC, Parham DM, Million L, Weiss AR, Barkauskas DA. Lymph node metastases in paediatric and young adult patients with non-rhabdomyosarcoma soft tissue sarcoma (NRSTS): Findings from Children's Oncology Group (COG) study ARST0332. Eur J Cancer. 2023 Feb;180:89-98. doi: 10.1016/j.ejca.2022.11.014. Epub 2022 Nov 25.

    PubMed 36566574

  • Venkatramani R, Xue W, Randall RL, Wolden S, Anderson J, Lopez-Terrada D, Black J, Kao SC, Shulkin B, Ostrenga A, Pappo A, Spunt SL. Synovial Sarcoma in Children, Adolescents, and Young Adults: A Report From the Children's Oncology Group ARST0332 Study. J Clin Oncol. 2021 Dec 10;39(35):3927-3937. doi: 10.1200/JCO.21.01628. Epub 2021 Oct 8.

    PubMed 34623899

  • Million L, Hayes-Jordan A, Chi YY, Donaldson SS, Wolden S, Morris C, Terezakis S, Laurie F, Morano K, Fitzgerald TJ, Yock TI, Rodeberg DA, Anderson JR, Speights RA, Black JO, Coffin C, McCarville MB, Kao SC, Hawkins DS, Spunt SL, Randall RL. Local Control For High-Grade Nonrhabdomyosarcoma Soft Tissue Sarcoma Assigned to Radiation Therapy on ARST0332: A Report From the Childrens Oncology Group. Int J Radiat Oncol Biol Phys. 2021 Jul 1;110(3):821-830. doi: 10.1016/j.ijrobp.2021.01.051. Epub 2021 Feb 3.

    PubMed 33548339

  • Spunt SL, Million L, Chi YY, Anderson J, Tian J, Hibbitts E, Coffin C, McCarville MB, Randall RL, Parham DM, Black JO, Kao SC, Hayes-Jordan A, Wolden S, Laurie F, Speights R, Kawashima E, Skapek SX, Meyer W, Pappo AS, Hawkins DS. A risk-based treatment strategy for non-rhabdomyosarcoma soft-tissue sarcomas in patients younger than 30 years (ARST0332): a Children's Oncology Group prospective study. Lancet Oncol. 2020 Jan;21(1):145-161. doi: 10.1016/S1470-2045(19)30672-2. Epub 2019 Nov 27.

    PubMed 31786124

  • Spunt SL, Francotte N, De Salvo GL, Chi YY, Zanetti I, Hayes-Jordan A, Kao SC, Orbach D, Brennan B, Weiss AR, van Noesel MM, Million L, Alaggio R, Parham DM, Kelsey A, Randall RL, McCarville MB, Bisogno G, Hawkins DS, Ferrari A. Clinical features and outcomes of young patients with epithelioid sarcoma: an analysis from the Children's Oncology Group and the European paediatric soft tissue Sarcoma Study Group prospective clinical trials. Eur J Cancer. 2019 May;112:98-106. doi: 10.1016/j.ejca.2019.02.001. Epub 2019 Apr 5.

    PubMed 30954717

  • Ferrari A, Chi YY, De Salvo GL, Orbach D, Brennan B, Randall RL, McCarville MB, Black JO, Alaggio R, Hawkins DS, Bisogno G, Spunt SL. Surgery alone is sufficient therapy for children and adolescents with low-risk synovial sarcoma: A joint analysis from the European paediatric soft tissue sarcoma Study Group and the Children's Oncology Group. Eur J Cancer. 2017 Jun;78:1-6. doi: 10.1016/j.ejca.2017.03.003. Epub 2017 Apr 7.

    PubMed 28391003

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing doxorubicin hydrochloride, clinical observation and therapeutic conventional surgery in people with Adult Alveolar Soft-part Sarcoma and Adult Angiosarcoma, run by Children's Oncology Group at 187 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 87 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 187 sites in United States, Canada, Australia, New Zealand, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Oct 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Probability for Event Free Survival. (time frame: 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00346164, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2022.

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