AzTrials
AzTrials

Alveolar Soft Part SarcomaPhase 2/3NCT02180867

Radiation Therapy With or Without Combination Chemotherapy or Pazopanib Before Surgery in Treating Patients With Newly Diagnosed Non-rhabdomyosarcoma Soft Tissue Sarcomas That Can Be Removed by Surgery

A Phase 2/3 study testing Doxorubicin, Doxorubicin Hydrochloride and Ifosfamide in people with Alveolar Soft Part Sarcoma and Angiomatoid Fibrous Histiocytoma, run by National Cancer Institute (NCI) at 381 sites in 3 countries.

Completed

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

Official record
Search all trials

Trial summary

This randomized phase II/III trial studies how well pazopanib, when combined with chemotherapy and radiation therapy or radiation therapy alone, work in the treatment of patients with newly diagnosed non-rhabdomyosarcoma soft tissue sarcomas that can eventually be removed by surgery. Read more about this study

Who is it for?
Ages 2 years and older
What is being tested?
Doxorubicin, Doxorubicin Hydrochloride and Ifosfamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
140 participants
Where
381 sitesin 3 countries
Study dates
12 Aug 2014to 31 Mar 2026
Phase
Phase 2/3
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 2 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Note: eligible patients must have a body surface area >= 0.5 m^2 AND be able to swallow whole tablets
  • Newly diagnosed and histopathologically confirmed, potentially resectable NRSTS of the extremity and trunk will be eligible for the chemotherapy or non-chemotherapy cohort based on:
  • Evidence of chemotherapy sensitivity of the histologic sarcoma subtype based on existing evidence from prior clinical trials
  • Sufficient risk of metastatic disease to warrant chemotherapy based on size and grade and
  • Medically deemed able or unable to undergo chemotherapy
  • Notes: an incisional biopsy or core biopsy is preferred; fine needle aspiration biopsy is not acceptable to establish the diagnosis
Show all 61Show fewer
  • ELIGIBLE SITES:
  • Extremities: upper (including shoulder) and lower (including hip)
  • Trunk: body wall
  • INELIGIBLE SITES: Head and neck, visceral organs (with the exception of embryonal sarcoma of the liver), retroperitoneum, peritoneum, pelvis within the confines of the bony pelvis
  • ELIGIBILITY FOR CHEMOTHERAPY COHORT:
  • Stage T2a/b (> 5 cm) and grade 2 or 3 AND
  • One of the following chemosensitive histologies as defined in the World Health Organization (WHO) classification of soft tissue tumors (with some evidence of good response to chemoradiation and of sufficient high risk of metastases, or clear evidence of metastases):
  • Unclassified soft tissue sarcomas that are too undifferentiated to be placed in a specific pathologic category in the WHO classification (often called "undifferentiated soft tissue sarcoma" or "soft tissue sarcoma not otherwise specified [NOS]")
  • Synovial sarcoma
  • Angiosarcoma of soft tissue
  • Adult fibrosarcoma
  • Mesenchymal (extraskeletal) chondrosarcoma
  • Leiomyosarcoma
  • Liposarcoma (excluding myxoid liposarcoma)
  • Undifferentiated pleomorphic sarcoma
  • Embryonal sarcoma of the liver
  • Patients meeting the above criteria (histology, size, and grade) with the EXCEPTION of histologies noted above may enroll on the chemotherapy cohort or the non-chemotherapy cohort at the discretion of the enrolling investigator; patients meeting these criteria with the EXCEPTION of histologies noted above but medically deemed unable to receive chemotherapy or who elect not to receive chemotherapy are eligible for the non-chemotherapy cohort
  • Patients with the following histologies are only eligible for the chemotherapy cohort and cannot enroll on the non-chemotherapy cohort:
  • Unclassified soft tissue sarcomas that are too undifferentiated to be placed in a specific pathologic category in the WHO classification (often called "undifferentiated soft tissue sarcoma" or "soft tissue sarcoma NOS") in patients < 30 years of age
  • Synovial sarcoma
  • Embryonal sarcoma of the liver
  • ELIGIBILITY FOR NON-CHEMOTHERAPY COHORT:
  • Patients with any size of grade 2 or 3 of the following "intermediate (rarely metastasizing)" or "malignant" tumors, as defined in the WHO classification of soft tissue tumors for which we have consensus data of chemotherapy-resistance are eligible only for the non-chemotherapy cohort:
  • So-called fibrohistiocytic tumors - plexiform fibrohistiocytic tumor, giant cell tumor of soft tissues
  • Fibroblastic/myofibroblastic tumors - solitary fibrous tumor, malignant solitary fibrous tumor, inflammatory myofibroblastic tumor, low grade myofibroblastic sarcoma, myxoinflammatory fibroblastic sarcoma, atypical myxoinflammatory fibroblastic tumor, myxofibrosarcoma, low grade fibromyxoid sarcoma, sclerosing epithelioid fibrosarcoma
  • Tumors of uncertain differentiation - epithelioid sarcoma, alveolar soft part sarcoma, clear cell sarcoma of soft tissue, angiomatoid fibrous histiocytoma, ossifying fibromyxoid tumor, myoepithelioma, myoepithelial carcinoma, extraskeletal myxoid chondrosarcoma, neoplasms with perivascular epithelioid cell differentiation (PEComa), intimal sarcoma, atypical fibroxanthoma, mixed tumor NOS, phosphaturic mesenchymal tumor, malignant ossifying fibromyxoid tumor, malignant mixed tumor, malignant phosphaturic mesenchymal tumor
  • Chondro-osseous tumors - extraskeletal osteosarcoma
  • Pericytic (perivascular) tumors - malignant glomus tumor
  • Nerve sheath tumors - malignant peripheral nerve sheath tumor, malignant granular cell tumor, epithelioid malignant peripheral nerve sheath tumor, malignant Triton tumor
  • Undifferentiated sarcomas (with a specific pathologic category in the WHO classification) - undifferentiated round cell sarcoma, undifferentiated epithelioid sarcoma, undifferentiated spindle cell sarcoma
  • Patients meeting the criteria (histology, size, and grade) with the EXCEPTION of histologies noted above may enroll on the non-chemotherapy cohort at the discretion of the enrolling investigator; patients meeting these criteria with the EXCEPTION of histologies noted above but medically deemed unable to receive chemotherapy or who elect not to receive chemotherapy are eligible for the non-chemotherapy cohort; note that tumors arising in bone are NOT eligible for this study
  • Extent of disease:
  • Patients with non-metastatic and metastatic disease are eligible
  • Initially unresectable patients, with or without metastatic disease, are eligible as long as there is a commitment at enrollment to resect the primary tumor
  • Sufficient tissue and blood must be available to submit for required biology studies
  • Lansky performance status score >= 70 for patients =< 16 years of age
  • Karnofsky performance status score >= 70 for patients > 16 years of age
  • Absolute neutrophil count >= 1500/uL; Note: no transfusions are permitted 7 days prior to laboratory studies to determine eligibility
  • Platelet count >= 100,000/uL; Note: no transfusions are permitted 7 days prior to laboratory studies to determine eligibility
  • Hemoglobin >= 8 g/dL for patients =< 16 years of age; >= 9 g/dL for patients > 16 years of age; Note: no transfusions are permitted 7 days prior to laboratory studies to determine eligibility
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or normal serum creatinine based on age/gender as follows:
  • 2 to < 6 years; 0.8 mg/dL male; 0.8 mg/dL female
  • 6 to < 10 years; 1 mg/dL male; 1 mg/dL female
  • 10 to < 13 years; 1.2 mg/dL male; 1.2 mg/dL female
  • 13 to < 16 years; 1.5 mg/dL male; 1.4 mg/dL female
  • >= 16 years; 1.5 mg/dL male; 1.4 mg/dL female
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x upper limit of normal (ULN) for age
  • Shortening fraction of >= 27% by echocardiogram OR ejection fraction of >= 50% by radionuclide angiogram
  • Corrected QT interval (QTc) < 480 msec
  • No evidence of dyspnea at rest, no exercise intolerance, and a resting pulse oximetry reading > 94% on room air if there is clinical indication for determination
  • Patients on low molecular weight heparin or Coumadin (with a stable international normalized ratio [INR]) are eligible
  • Patient must have a life expectancy of at least 3 months with appropriate therapy
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Who cannot join

  • Patients with grade 1 NRSTS tumors of any size are not eligible
  • Patients with known central nervous system (CNS) metastases are not eligible; Note: brain imaging is not an eligibility requirement
  • Patients with evidence of active bleeding or bleeding diathesis will be excluded (Note: patients aged > 17 years with excess of 2.5 mL of hemoptysis are not eligible)
  • Patients with gross total resection of the primary tumor prior to enrollment on ARST1321 are NOT eligible; patients who have experienced tumor recurrence after a gross total tumor resection are NOT eligible
  • Patients with uncontrolled hypertension are ineligible; uncontrolled hypertension is defined as follows:
  • Patients aged =< 17 years: greater than 95th percentile systolic and diastolic blood pressure based on age and height which is not controlled by one anti-hypertensive medication
Show all 48Show fewer
  • Patients aged > 17 years: systolic blood pressure >= 140 mmHg and/or diastolic blood pressure >= 90 mmHg that is not controlled by one anti-hypertensive medication
  • Prior Therapy:
  • Patients must have had no prior anthracycline (e.g., doxorubicin, daunorubicin) or ifosfamide chemotherapy
  • Patients must have had no prior use of pazopanib or similar multi-targeted tyrosine kinase inhibitors (TKI)
  • Patients must have had no prior radiotherapy to tumor-involved sites
  • Note: patients previously treated for a non-NRSTS cancer are eligible provided they meet the prior therapy requirements; patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier are excluded
  • Other types of invasive malignancy that are not disease free within 3 years except for non-melanoma skin cancer, lentigo maligna, any carcinoma-in-situ or prostate cancer with low risk factors
  • CYTOCHROME P450 3A4 (CYP3A4) substrates WITH narrow therapeutic indices: patients chronically receiving medications known to be metabolized by CYP3A4 and with narrow therapeutic indices within 7 days prior to study enrollment, including but not limited to pimozide, aripiprazole, triazolam, ergotamine and halofantrine are not eligible; Note: the use of fentanyl is permitted
  • CYP3A4 Inhibitors: patients chronically receiving drugs that are known potent CYP3A4 inhibitors within 7 days prior to study enrollment, including but not limited to itraconazole, clarithromycin, erythromycin many non-nucleoside reverse-transcriptase inhibitors (NNRTIs), diltiazem, verapamil, and grapefruit juice are not eligible
  • CYP3A4 Inducers: patients chronically receiving drugs that are known potent CYP3A4 inducers within 14 days prior to study enrollment, including but not limited to carbamazepine, phenobarbital, phenytoin, rifampin, and St. John's wort are not eligible (with the exception of glucocorticoids)
  • Certain medications that are associated with a risk for QTc prolongation and/or Torsades de Pointes, although not prohibited, should be avoided or replaced with medications that do not carry these risks, if possible
  • Subjects with any condition that may impair the ability to swallow or absorb oral medications/investigational product including:
  • Any lesion, whether induced by tumor, radiation or other conditions, which makes it difficult to swallow capsules or pills
  • Prior surgical procedures affecting absorption including, but not limited to major resection of stomach or small bowel
  • Active peptic ulcer disease
  • Malabsorption syndrome
  • Subjects with any condition that may increase the risk of gastrointestinal bleeding or gastrointestinal perforation, including:
  • Active peptic ulcer disease
  • Known intraluminal metastatic lesions
  • Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or other gastrointestinal conditions which increase the risk of perforation
  • History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to beginning study treatment
  • Subjects with any of the following cardiovascular conditions within the past 6 months
  • Cerebrovascular accident (CVA) or transient ischemic attack (TIA)
  • Cardiac arrhythmia
  • Admission for unstable angina
  • Cardiac angioplasty or stenting
  • Coronary artery bypass graft surgery
  • Pulmonary embolism, untreated deep venous thrombosis (DVT) or DVT which has been treated with therapeutic anticoagulation for less than 6 weeks
  • Arterial thrombosis
  • Symptomatic peripheral vascular disease
  • Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system; a subject who has a history of class II heart failure and is asymptomatic on treatment may be considered eligible
  • History of serious or non-healing wound, ulcer, or bone fracture
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients who are unable to swallow whole tablets are not eligible
  • Patients with a body surface area < 0.5 m^2 are not eligible
  • Human immunodeficiency virus (HIV)-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pazopanib; in addition, these subjects are at increased risk of lethal infections when treated with marrow-suppressive therapy
  • Patients who are receiving any other investigational agent(s)
  • Pregnancy and breast feeding:
  • Female patients who are pregnant are ineligible due to risks of fetal and teratogenic adverse events as seen in animal/human studies
  • Lactating females are not eligible unless they have agreed not to breastfeed their infants during treatment and for a period of 1 month following completion of treatment
  • Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
  • Unwillingness to use an effective contraceptive method for the duration of their study participation and for at least 1 month after treatment is completed if sexually active with reproductive potential

Trial locations and contacts

381 sites in 3 countries.

316 sites in 3 countries

United States300 sites

  • Providence Regional Cancer System-Aberdeen

    Aberdeen, Washington, 98520

  • 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

  • Lehigh Valley Hospital-Cedar Crest

    Allentown, Pennsylvania, 18103

  • Kaiser Permanente-Anaheim

    Anaheim, California, 92806

  • Anchorage Associates in Radiation Medicine

    Anchorage, Alaska, 98508

  • Alaska Breast Care and Surgery LLC

    Anchorage, Alaska, 99508

  • Alaska Oncology and Hematology LLC

    Anchorage, Alaska, 99508

  • Alaska Women's Cancer Care

    Anchorage, Alaska, 99508

  • Anchorage Oncology Centre

    Anchorage, Alaska, 99508

  • Katmai Oncology Group

    Anchorage, Alaska, 99508

  • Providence Alaska Medical Center

    Anchorage, Alaska, 99508

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • Mission Hospital

    Asheville, North Carolina, 28801

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Children's Healthcare of Atlanta - Arthur M Blank Hospital

    Atlanta, Georgia, 30329

  • Augusta University Medical Center

    Augusta, Georgia, 30912

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • Dell Children's Medical Center of Central Texas

    Austin, Texas, 78723

  • AIS Cancer Center at San Joaquin Community Hospital

    Bakersfield, California, 93301

  • Sinai Hospital of Baltimore

    Baltimore, Maryland, 21215

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Eastern Maine Medical Center

    Bangor, Maine, 04401

  • Bronson Battle Creek

    Battle Creek, Michigan, 49017

  • UHHS-Chagrin Highlands Medical Center

    Beachwood, Ohio, 44122

  • Indu and Raj Soin Medical Center

    Beavercreek, Ohio, 45431

  • PeaceHealth Saint Joseph Medical Center

    Bellingham, Washington, 98225

  • Saint Charles Health System

    Bend, Oregon, 97701

  • Central Vermont Medical Center/National Life Cancer Treatment

    Berlin Corners, Vermont, 05602

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889-5600

  • Lehigh Valley Hospital - Muhlenberg

    Bethlehem, Pennsylvania, 18017

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • The Kirklin Clinic at Acton Road

    Birmingham, Alabama, 35243

  • Prisma Health Cancer Institute - Spartanburg

    Boiling Springs, South Carolina, 29316

  • Saint Luke's Cancer Institute - Boise

    Boise, Idaho, 83712

  • Central Care Cancer Center - Bolivar

    Bolivar, Missouri, 65613

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Henry Ford Cancer Institute-Downriver

    Brownstown, Michigan, 48183

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Providence Saint Joseph Medical Center/Disney Family Cancer Center

    Burbank, California, 91505

  • University of Vermont Medical Center

    Burlington, Vermont, 05401

  • University of Vermont and State Agricultural College

    Burlington, Vermont, 05405

  • Aurora Cancer Care-Southern Lakes VLCC

    Burlington, Wisconsin, 53105

  • Dayton Physicians LLC-Miami Valley South

    Centerville, Ohio, 45459

  • Miami Valley Hospital South

    Centerville, Ohio, 45459

  • Providence Regional Cancer System-Centralia

    Centralia, Washington, 98531

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • West Virginia University Charleston Division

    Charleston, West Virginia, 25304

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • Novant Health Presbyterian Medical Center

    Charlotte, North Carolina, 28204

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • T C Thompson Children's Hospital

    Chattanooga, Tennessee, 37403

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60611

  • Northwestern University

    Chicago, Illinois, 60611

  • Rush MD Anderson Cancer Center

    Chicago, Illinois, 60612

  • University of Illinois

    Chicago, Illinois, 60612

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Oncology Hematology Care Inc-Kenwood

    Cincinnati, Ohio, 45236

  • Oncology Hematology Care Inc-Blue Ash

    Cincinnati, Ohio, 45242

  • Clackamas Radiation Oncology Center

    Clackamas, Oregon, 97015

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Rainbow Babies and Childrens Hospital

    Cleveland, Ohio, 44106

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Henry Ford Macomb Hospital-Clinton Township

    Clinton Township, Michigan, 48038

  • UCHealth Memorial Hospital Central

    Colorado Springs, Colorado, 80909

  • University of Missouri Children's Hospital

    Columbia, Missouri, 65212

  • Prisma Health Richland Hospital

    Columbia, South Carolina, 29203

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Bay Area Hospital

    Coos Bay, Oregon, 97420

  • Driscoll Children's Hospital

    Corpus Christi, Texas, 78411

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • Medical City Dallas Hospital

    Dallas, Texas, 75230

  • Parkland Memorial Hospital

    Dallas, Texas, 75235

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

  • Dayton Children's Hospital

    Dayton, Ohio, 45404

  • Good Samaritan Hospital - Dayton

    Dayton, Ohio, 45406

  • Miami Valley Hospital

    Dayton, Ohio, 45409

  • Dayton Physician LLC - Englewood

    Dayton, Ohio, 45415

  • Miami Valley Hospital North

    Dayton, Ohio, 45415

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

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

    Denver, Colorado, 80218

  • Blank Children's Hospital

    Des Moines, Iowa, 50309

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • UI Health Care Mission Cancer and Blood - Des Moines Clinic

    Des Moines, Iowa, 50309

  • Broadlawns Medical Center

    Des Moines, Iowa, 50314

  • Iowa Lutheran Hospital

    Des Moines, Iowa, 50316

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Henry Ford Health Saint John Hospital

    Detroit, Michigan, 48236

  • Kaiser Permanente Downey Medical Center

    Downey, California, 90242

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Essentia Health Cancer Center

    Duluth, Minnesota, 55805

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Michigan State University

    East Lansing, Michigan, 48823

  • El Paso Children's Hospital

    El Paso, Texas, 79905

  • Newman Regional Health

    Emporia, Kansas, 66801

  • Providence Regional Cancer Partnership

    Everett, Washington, 98201

  • Inova Fairfax Hospital

    Falls Church, Virginia, 22042

  • Sanford Broadway Medical Center

    Fargo, North Dakota, 58122

  • Armes Family Cancer Center

    Findlay, Ohio, 45840

  • Blanchard Valley Hospital

    Findlay, Ohio, 45840

  • Orion Cancer Care

    Findlay, Ohio, 45840

  • Hurley Medical Center

    Flint, Michigan, 48503

  • Aurora Health Center-Fond du Lac

    Fond du Lac, Wisconsin, 54937

  • Poudre Valley Hospital

    Fort Collins, Colorado, 80524

  • Golisano Children's Hospital of Southwest Florida

    Fort Myers, Florida, 33908

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

  • Atrium Medical Center-Middletown Regional Hospital

    Franklin, Ohio, 45005-1066

  • Dayton Physicians LLC-Atrium

    Franklin, Ohio, 45005

  • Saint Luke's Cancer Institute - Fruitland

    Fruitland, Idaho, 83619

  • UF Health Cancer Institute - Gainesville

    Gainesville, Florida, 32610

  • Central Care Cancer Center - Garden City

    Garden City, Kansas, 67846

  • Saint Catherine Hospital

    Garden City, Kansas, 67846

  • Northwestern Medicine Cancer Center Delnor

    Geneva, Illinois, 60134

  • Aurora Health Care Germantown Health Center

    Germantown, Wisconsin, 53022

  • Glens Falls Hospital

    Glens Falls, New York, 12801

  • Aurora Cancer Care-Grafton

    Grafton, Wisconsin, 53024

  • Corewell Health Grand Rapids Hospitals - Butterworth Hospital

    Grand Rapids, Michigan, 49503

  • Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

    Grand Rapids, Michigan, 49503

  • Trinity Health Grand Rapids Hospital

    Grand Rapids, Michigan, 49503

  • Central Care Cancer Center - Great Bend

    Great Bend, Kansas, 67530

  • Saint Rose Ambulatory and Surgery Center

    Great Bend, Kansas, 67530

  • Aurora BayCare Medical Center

    Green Bay, Wisconsin, 54311

  • East Carolina University

    Greenville, North Carolina, 27834

  • Dayton Physicians LLC-Wayne

    Greenville, Ohio, 45331

  • Wayne Hospital

    Greenville, Ohio, 45331

  • Greenville Health System Cancer Institute-Andrews

    Greenville, South Carolina, 29601

  • Saint Francis Hospital

    Greenville, South Carolina, 29601

  • BI-LO Charities Children's Cancer Center

    Greenville, South Carolina, 29605

  • Prisma Health Cancer Institute - Butternut

    Greenville, South Carolina, 29605

  • Prisma Health Cancer Institute - Faris

    Greenville, South Carolina, 29605

  • Prisma Health Greenville Memorial Hospital

    Greenville, South Carolina, 29605

  • Saint Francis Cancer Center

    Greenville, South Carolina, 29607

  • Prisma Health Cancer Institute - Eastside

    Greenville, South Carolina, 29615

  • Prisma Health Cancer Institute - Greer

    Greer, South Carolina, 29650

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Connecticut Children's Medical Center

    Hartford, Connecticut, 06106

  • HaysMed

    Hays, Kansas, 67601

  • Oncology Las Vegas - Henderson

    Henderson, Nevada, 89074

  • Penn State Children's Hospital

    Hershey, Pennsylvania, 17033

  • Memorial Regional Hospital/Joe DiMaggio Children's Hospital

    Hollywood, Florida, 33021

  • Straub Clinic and Hospital

    Honolulu, Hawaii, 96813

  • Kaiser Permanente Moanalua Medical Center

    Honolulu, Hawaii, 96819

  • Kapiolani Medical Center for Women and Children

    Honolulu, Hawaii, 96826

  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

    Houston, Texas, 77030

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • Ascension Saint Vincent Indianapolis Hospital

    Indianapolis, Indiana, 46260

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • Swedish Cancer Institute-Issaquah

    Issaquah, Washington, 98029

  • Allegiance Health

    Jackson, Michigan, 49201

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Nemours Children's Clinic-Jacksonville

    Jacksonville, Florida, 32207

  • Freeman Health System

    Joplin, Missouri, 64804

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007

  • Beacon Kalamazoo

    Kalamazoo, Michigan, 49048

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • Children's Mercy Hospitals and Clinics

    Kansas City, Missouri, 64108

  • The University of Kansas Cancer Center-South

    Kansas City, Missouri, 64131

  • Research Medical Center

    Kansas City, Missouri, 64132

  • University of Kansas Cancer Center - North

    Kansas City, Missouri, 64154

  • Kadlec Clinic Hematology and Oncology

    Kennewick, Washington, 99336

  • Aurora Cancer Care-Kenosha South

    Kenosha, Wisconsin, 53142

  • Greater Dayton Cancer Center

    Kettering, Ohio, 45409

  • Kettering Medical Center

    Kettering, Ohio, 45429

  • East Tennessee Childrens Hospital

    Knoxville, Tennessee, 37916

  • Providence Regional Cancer System-Lacey

    Lacey, Washington, 98503

  • University of Michigan Health - Sparrow Lansing

    Lansing, Michigan, 48912

  • Radiation Oncology Centers of Nevada Central

    Las Vegas, Nevada, 89106

  • Alliance for Childhood Diseases/Cure 4 the Kids Foundation

    Las Vegas, Nevada, 89135

  • Summerlin Hospital Medical Center

    Las Vegas, Nevada, 89144

  • Comprehensive Cancer Centers of Nevada

    Las Vegas, Nevada, 89148

  • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

    Lebanon, New Hampshire, 03756

  • University of Kansas Cancer Center - Lee's Summit

    Lee's Summit, Missouri, 64064

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202-3591

  • Loma Linda University Medical Center

    Loma Linda, California, 92354

  • Miller Children's and Women's Hospital Long Beach

    Long Beach, California, 90806

  • PeaceHealth Saint John Medical Center

    Longview, Washington, 98632

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Kaiser Permanente Los Angeles Medical Center

    Los Angeles, California, 90027

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • UCLA / Jonsson Comprehensive Cancer Center

    Los Angeles, California, 90095

  • Norton Children's Hospital

    Louisville, Kentucky, 40202

  • Norton Hospital Pavilion and Medical Campus

    Louisville, Kentucky, 40202

  • Norton Suburban Hospital and Medical Campus

    Louisville, Kentucky, 40207

  • Covenant Children's Hospital

    Lubbock, Texas, 79410

  • UMC Cancer Center / UMC Health System

    Lubbock, Texas, 79415

  • Texas Tech University Health Sciences Center-Lubbock

    Lubbock, Texas, 79430

  • Valley Children's Hospital

    Madera, California, 93636

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

  • Aurora Bay Area Medical Group-Marinette

    Marinette, Wisconsin, 54143

  • Marshfield Medical Center-Marshfield

    Marshfield, Wisconsin, 54449

  • Matthews Radiation Oncology Center

    Matthews, North Carolina, 28105

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • Saint Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Saint Luke's Cancer Institute - Meridian

    Meridian, Idaho, 83642

  • Banner Children's at Desert

    Mesa, Arizona, 85202

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

    Miami, Florida, 33136

  • Nicklaus Children's Hospital

    Miami, Florida, 33155

  • Aurora Cancer Care-Milwaukee

    Milwaukee, Wisconsin, 53209

  • Aurora Saint Luke's Medical Center

    Milwaukee, Wisconsin, 53215

  • Children's Hospital of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Aurora Sinai Medical Center

    Milwaukee, Wisconsin, 53233

  • NYU Langone Hospital - Long Island

    Mineola, New York, 11501

  • Children's Hospitals and Clinics of Minnesota - Minneapolis

    Minneapolis, Minnesota, 55404

  • University of Minnesota/Masonic Cancer Center

    Minneapolis, Minnesota, 55455

  • West Virginia University Healthcare

    Morgantown, West Virginia, 26506

  • Morristown Medical Center

    Morristown, New Jersey, 07960

  • SSM Health Good Samaritan

    Mount Vernon, Illinois, 62864

  • Trinity Health Muskegon Hospital

    Muskegon, Michigan, 49444

  • Saint Luke's Cancer Institute - Nampa

    Nampa, Idaho, 83687

  • The Children's Hospital at TriStar Centennial

    Nashville, Tennessee, 37203

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Saint Peter's University Hospital

    New Brunswick, New Jersey, 08901

  • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

    New Brunswick, New Jersey, 08903

  • Yale University

    New Haven, Connecticut, 06520

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

    New Hyde Park, New York, 11040

  • UC Comprehensive Cancer Center at Silver Cross

    New Lenox, Illinois, 60451

  • Children's Hospital New Orleans

    New Orleans, Louisiana, 70118

  • Ochsner Medical Center Jefferson

    New Orleans, Louisiana, 70121

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone

    New York, New York, 10016

  • Mount Sinai Hospital

    New York, New York, 10029

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • NYP/Weill Cornell Medical Center

    New York, New York, 10065

  • Newark Beth Israel Medical Center

    Newark, New Jersey, 07112

  • Corewell Health Lakeland Hospitals - Niles Hospital

    Niles, Michigan, 49120

  • Children's Hospital of The King's Daughters

    Norfolk, Virginia, 23507

  • Advocate Children's Hospital-Oak Lawn

    Oak Lawn, Illinois, 60453

  • UCSF Benioff Children's Hospital Oakland

    Oakland, California, 94609

  • Kaiser Permanente-Oakland

    Oakland, California, 94611

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Mercy Hospital Oklahoma City

    Oklahoma City, Oklahoma, 73120

  • The University of Kansas Cancer Center - Olathe

    Olathe, Kansas, 66061

  • Children's Hospital and Medical Center of Omaha

    Omaha, Nebraska, 68114

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Children's Hospital of Orange County

    Orange, California, 92868

  • AdventHealth Orlando

    Orlando, Florida, 32803

  • Nemours Children's Hospital

    Orlando, Florida, 32827

  • Vince Lombardi Cancer Clinic - Oshkosh

    Oshkosh, Wisconsin, 54904

  • University of Kansas Cancer Center-Overland Park

    Overland Park, Kansas, 66210

  • Lucile Packard Children's Hospital Stanford University

    Palo Alto, California, 94304

  • Stanford Cancer Institute Palo Alto

    Palo Alto, California, 94304

  • Advocate Children's Hospital-Park Ridge

    Park Ridge, Illinois, 60068

  • Saint Joseph's Regional Medical Center

    Paterson, New Jersey, 07503

  • Nemours Children's Clinic - Pensacola

    Pensacola, Florida, 32504

  • OSF Children's Hospital of Illinois

    Peoria, Illinois, 61637

  • Drexel University School of Medicine

    Philadelphia, Pennsylvania, 19102

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Saint Christopher's Hospital for Children

    Philadelphia, Pennsylvania, 19134

  • Phoenix Childrens Hospital

    Phoenix, Arizona, 85016

  • Mercy Hospital Pittsburg

    Pittsburg, Kansas, 66762

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • Providence Portland Medical Center

    Portland, Oregon, 97213

  • Providence Saint Vincent Medical Center

    Portland, Oregon, 97225

  • Legacy Emanuel Children's Hospital

    Portland, Oregon, 97227

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • Aurora Cancer Care-Racine

    Racine, Wisconsin, 53406

  • Corewell Health Reed City Hospital

    Reed City, Michigan, 49677

  • Renown Regional Medical Center

    Reno, Nevada, 89502

  • Saint Mary's Regional Medical Center

    Reno, Nevada, 89503

  • Radiation Oncology Associates

    Reno, Nevada, 89509

  • Reid Health

    Richmond, Indiana, 47374

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

  • Kaiser Permanente-Riverside

    Riverside, California, 92505

  • Carilion Children's

    Roanoke, Virginia, 24014

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • University of Rochester

    Rochester, New York, 14642

  • Mercy Clinic-Rolla-Cancer and Hematology

    Rolla, Missouri, 65401

  • Phelps Health Delbert Day Cancer Institute

    Rolla, Missouri, 65401

  • Corewell Health Children's

    Royal Oak, Michigan, 48073

  • Sutter Medical Center Sacramento

    Sacramento, California, 95816

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center

    Saint Joseph, Michigan, 49085

  • Corewell Health Lakeland Hospitals - Saint Joseph Hospital

    Saint Joseph, Michigan, 49085

  • Salina Regional Health Center

    Salina, Kansas, 67401

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • Primary Children's Hospital

    Salt Lake City, Utah, 84113

  • Children's Hospital of San Antonio

    San Antonio, Texas, 78207

  • Methodist Children's Hospital of South Texas

    San Antonio, Texas, 78229

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • Kaiser Permanente-San Diego Zion

    San Diego, California, 92120

  • Rady Children's Hospital - San Diego

    San Diego, California, 92123

Other trials in United States

Canada14 sites

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • IWK Health Centre

    Halifax, Nova Scotia, B3K 6R8

  • McMaster Children's Hospital at Hamilton Health Sciences

    Hamilton, Ontario, L8N 3Z5

  • Children's Hospital

    London, Ontario, N6A 5W9

  • CIUSSSEMTL-Hopital Maisonneuve-Rosemont

    Montreal, Quebec, H1T 2M4

  • CHUM - Centre Hospitalier de l'Universite de Montreal

    Montreal, Quebec, H2X 3E4

  • The Montreal Children's Hospital of the MUHC

    Montreal, Quebec, H3H 1P3

  • Centre Hospitalier Universitaire Sainte-Justine

    Montreal, Quebec, H3T 1C5

  • CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)

    Québec, G1V 4G2

  • Allan Blair Cancer Centre

    Regina, Saskatchewan, S4T 7T1

  • Janeway Child Health Centre

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

  • 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

Puerto Rico2 sites

  • San Jorge Children's Hospital

    San Juan, 00912

  • University Pediatric Hospital

    San Juan, 00926

Other trials in Puerto Rico

About this study

Official title: Pazopanib Neoadjuvant Trial in Non-Rhabdomyosarcoma Soft Tissue Sarcomas (PAZNTIS): A Phase II/III Randomized Trial of Preoperative Chemoradiation or Preoperative Radiation Plus or Minus Pazopanib (NSC# 737754)

This randomized phase II/III trial studies how well pazopanib, when combined with chemotherapy and radiation therapy or radiation therapy alone, work in the treatment of patients with newly diagnosed non-rhabdomyosarcoma soft tissue sarcomas that can eventually be removed by surgery. 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, by stopping them from dividing, or by stopping them from spreading. Pazopanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether these therapies can be safely combined and if they work better when given together in treating patients with non-rhabdomyosarcoma soft tissue sarcomas.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To identify the dose of pazopanib that is feasible when given in combination with radiation or chemoradiation in pediatric and adult patients newly diagnosed with unresected intermediate- and high-risk non rhabdomyosarcoma soft tissue sarcomas (NRSTS).

II. To compare the rates of near complete pathologic response (> 90% necrosis) with the addition of pazopanib to preoperative chemoradiation versus preoperative chemoradiation alone for potentially resectable > 5 cm, grade 2 or 3 intermediate to high risk chemotherapy-sensitive NRSTS in the phase II portion of the study for this cohort.

III. To compare the rates of near complete pathologic response (> 90% necrosis) with the addition of pazopanib to preoperative radiotherapy versus preoperative radiotherapy alone for potentially resectable intermediate to high risk adult and pediatric NRSTS in the phase II portion of the study for this cohort (using a phase II decision rule to go onto the phase III portion of the study).

IV. To compare the rates of event-free survival (EFS) with the addition of pazopanib to preoperative radiotherapy versus preoperative radiotherapy alone for localized intermediate to high risk adult and pediatric NRSTS in the phase III portion of the study for this cohort if the phase II decision rule is passed.

SECONDARY OBJECTIVES:

  1. To estimate the rates of local failure, regional failure, distant metastasis free survival, disease-free survival, and overall survival with the addition of pazopanib to preoperative chemoradiation or preoperative radiation in intermediate to high risk adult and pediatric NRSTS.

II. To compare the pattern of recurrence (local, regional and distant) between preoperative chemoradiation or radiation with the addition of pazopanib for adult and pediatric NRSTS.

III. To define the toxicities of ifosfamide and doxorubicin chemotherapy and radiation when used in combination with pazopanib in intermediate to high risk adult and pediatric NRSTS.

IV. To define the toxicities of preoperative radiotherapy when used in combination with pazopanib in intermediate to high risk adult and pediatric NRSTS.

EXPLORATORY OBJECTIVES:

  1. To gain insight into the disease biology of childhood and adult NRSTS through analysis of actionable mutations and whole genome sequencing.

II. To determine if microvessel density and circulating tumor deoxyribonucleic acid (DNA) predict response to pazopanib and outcome.

III. To determine the effect of pazopanib on doxorubicin exposure in children and adults with NRSTS.

IV. To evaluate change in fludeoxyglucose F 18 (FDG) positron emission tomography (PET) maximum standard uptake value (SUVmax) from baseline to week 10 or 13 in patients with unresected tumors and to correlate this change with pathologic response and EFS.

  1. To compare the rate of response by standard imaging and pathologic assessment to determine which correlates better with local tumor control, distant tumor control, EFS, and overall survival.

OUTLINE: This study starts as a dose-escalation study of pazopanib.

CHEMOTHERAPY COHORT: Patients eligible for chemotherapy cohort are randomized to 1 of 2 treatment regimens.

REGIMEN A:

INDUCTION PHASE: Patients receive pazopanib orally (PO) once daily (QD) on weeks 1-12, ifosfamide intravenously (IV) over 2-4 hours on days 1-3 on weeks 1, 4, 7, 10, and doxorubicin IV over 1-15 minutes on days 1-2 on weeks 1 and 4. At least 24 hours after the completion of week 4 doxorubicin, patients undergo radiation therapy on weeks 4-10.

SURGERY: Patients undergo surgery on week 13.

CONTINUATION PHASE: Patients receive pazopanib PO QD on weeks 16-25, ifosfamide IV over 2-4 hours on days 1-3 on weeks 16 and 19, and doxorubicin IV over 1-15 minutes on days 1-2 on weeks 16, 19, and 22. If applicable, patients undergo additional radiation therapy at week 16

REGIMEN B:

INDUCTION PHASE: Patients receive ifosfamide IV over 2-4 hours on days 1-3 on weeks 1, 4, 7, 10 and doxorubicin hydrochloride IV over 1-15 minutes on days 1-2 on weeks 1 and 4. At least 24 hours after the completion of week 4 doxorubicin, patients undergo radiation therapy on weeks 4-10.

SURGERY: Patients undergo surgery on week 13.

CONTINUATION PHASE: Patients receive ifosfamide IV over 2-4 hours on days 1-3 on weeks 16 and 19 and doxorubicin IV over 1-15 minutes on days 1-2 on weeks 16, 19, and 22. If applicable, patients undergo additional radiation therapy at week 16.

NON-CHEMOTHERAPY COHORT: Patients eligible for non-chemotherapy cohort are randomized to 1 of 2 treatment regimens.

REGIMEN C:

INDUCTION PHASE: Patients receive pazopanib PO QD on weeks 1-9. Patients undergo radiation therapy on weeks 1-7.

SURGERY: Patients undergo surgery on week 10.

CONTINUATION PHASE: Patients receive pazopanib PO QD on weeks 13-25. If applicable, patients undergo additional radiation therapy at week 13.

REGIMEN D:

INDUCTION PHASE: Patients undergo radiation therapy on weeks 1-7.

SURGERY: Patients undergo surgery on week 10.

CONTINUATION PHASE: If applicable, patients undergo additional radiation therapy at week 13.

After completion of study treatment, patients are followed up at 6, 12, 18, 24, 30, 36, 48, and 60 months.

Being tested
Doxorubicin, Doxorubicin Hydrochloride, Ifosfamide, Pazopanib, Pazopanib Hydrochloride
Medical subject headings
Sarcoma, Alveolar Soft Part, Histiocytoma, Angiomatoid Fibrous, Sarcoma, Clear Cell, Sarcoma, Chondrosarcoma, Extraskeletal Myxoid, Fibrosarcoma, Granuloma, Plasma Cell, Leiomyosarcoma

What participants receive

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

  • DoxorubicinDrug

    Also called Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin

    Given IV

  • Doxorubicin HydrochlorideDrug

    Also called 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin

    Given IV

  • IfosfamideDrug

    Also called Asta Z 4942, Asta Z-4942, Cyfos, Holoxan

    Given IV

  • PazopanibDrug

    Also called GW786034

    Given PO

  • Pazopanib HydrochlorideDrug

    Also called GW 786034B, GW-786034B, GW786034B, Pazopater

    Given PO

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate

    Undergo radiation therapy

  • Therapeutic Conventional SurgeryProcedure or surgery

    Undergo surgery

Study groups in NCT02180867
Study groupRoleWhat they receive
Regimen A (pazopanib, chemoradiation)ExperimentalSee Regimen A Detailed Description.
Receives: Drug: Doxorubicin; Drug: Doxorubicin Hydrochloride; Drug: Ifosfamide; Drug: Pazopanib; Drug: Pazopanib Hydrochloride; Radiation: Radiation Therapy; Procedure: Therapeutic Conventional Surgery
Regimen B (chemoradiation)ExperimentalSee Regimen B Detailed Description.
Receives: Drug: Doxorubicin; Drug: Doxorubicin Hydrochloride; Drug: Ifosfamide; Radiation: Radiation Therapy; Procedure: Therapeutic Conventional Surgery
Regimen C (pazopanib, radiation therapy)ExperimentalINDUCTION PHASE: Patients receive pazopanib PO QD on weeks 1-9. Patients undergo radiation therapy on weeks 1-7. SURGERY: Patients undergo surgery on week 10. CONTINUATION PHASE: Patients receive pazopanib PO QD on weeks 13-25. If applicable, patients undergo additional radiation therapy at week 13.
Receives: Drug: Pazopanib; Drug: Pazopanib Hydrochloride; Radiation: Radiation Therapy; Procedure: Therapeutic Conventional Surgery
Regimen D (radiation therapy)ExperimentalINDUCTION PHASE: Patients undergo radiation therapy on weeks 1-7. SURGERY: Patients undergo surgery on week 10. CONTINUATION PHASE: If applicable, patients undergo additional radiation therapy at week 13.
Receives: Radiation: Radiation Therapy; Procedure: Therapeutic Conventional Surgery

What is being measured

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

  1. Feasible Dose: Pediatric

    The dose of pazopanib that is feasible when given in combination with radiation or chemoradiation in pediatric unresected intermediate- and high-risk NRSTS patients. Initially, up to 10 patients (minimum of 3 patients ≥ 2 and < 18 years of age and 3 patients ≥ 18 years of age) eligible for each of the two study cohorts were non-randomly assigned (to generate 8 patients evaluable for toxicity) to receive treatment with pazopanib at dose level 1. A protocol-defined list of pazopanib-associated adverse events were defined as dose-limiting toxicities. The pazopanib dose determined to be feasible was based on the number of patient-reported dose-limiting toxicities encountered.

    Measured: After the first 6 weeks of Induction

  2. Feasible Dose: Adult

    The dose of pazopanib that is feasible when given in combination with radiation or chemoradiation in adult unresected intermediate- and high-risk NRSTS patients. Initially, up to 10 patients (minimum of 3 patients ≥ 2 and < 18 years of age and 3 patients ≥ 18 years of age) eligible for each of the two study cohorts were non-randomly assigned (to generate 8 patients evaluable for toxicity) to receive treatment with pazopanib at dose level 1. A protocol-defined list of pazopanib-associated adverse events were defined as dose-limiting toxicities. The pazopanib dose determined to be feasible was based on the number of patient-reported dose-limiting toxicities encountered.

    Measured: After the first 6 weeks of Induction

  3. Percentage of Chemoradiotherapy Patients With Positive Pathologic Response at Week 13

    A responder is defined by more than (90% tumor necrosis at week 13). A non-responder has less than 90% necrosis or progressive disease before week 13.

    Measured: Week 13 after induction

  4. Percentage of Radiotherapy Patients With Positive Pathologic Response at Week 10

    A responder is defined by more than 90% tumor necrosis at week 10. A non-responder has less than 90% necrosis or progressive disease before week 10.

    Measured: Week 10 after induction

  5. Percentage of Radiotherapy Patients Failure Free at 5 Years Following Study Entry

    Time to the first occurrence of relapse, progression, secondary cancer or death from any cause.

    Measured: From enrollment to up to 60 months

Secondary outcomes (4)

  1. Percentage of Patients Local Failure Free at 5 Years Following Study Entry

    Defined as disease recurrence only at the primary site of disease at diagnosis. The relative risk of specific failure types will be estimated and compared descriptively using the Cox proportional hazard model. Data were obtained from institutional reported data.

    Measured: From enrollment to up to 60 months

  2. Percentage of Patients Regional Failure Free at 5 Years Following Study Entry

    Defined as disease recurrence at lymph nodes regional to the primary disease site, with or without local failure but without distant failure. The relative risk of specific failure types will be estimated and compared descriptively using the Cox proportional hazard model. Data were obtained from institutional reported data.

    Measured: From enrollment to up to 60 months

  3. Percentage of Patients Distant Failure Free at 5 Years Following Study Entry

    Defined as disease recurrence at sites other than the primary site and diagnosis and nodes regional to that site (metastatic disease, whether or not present at diagnosis), with or without loco-regional failure. The relative risk of specific failure types will be estimated and compared descriptively using the Cox proportional hazard model. Data were obtained from institutional reported data.

    Measured: From enrollment to up to 60 months

  4. Percentage of Patients Who Experienced Grade 3 or Higher Toxicity Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)

    Participants who experienced Grade 3 or higher toxicity was assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).

    Measured: Reporting of adverse events was required from the start of protocol therapy and until 30 days from the last administration of study drugs; up to 1 year

Timeline

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

  1. First posted3 Jul 2014 (estimated)
  2. Study start12 Aug 2014
  3. Primary completion30 Jun 2019
  4. Study completion31 Mar 2026

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
140 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02180867
Sponsor's protocol ID
NCI-2014-01340
Other IDs
NCI-2014-01340, ARST1321, s14-02023, ARST1321, ARST1321, U10CA098543, U10CA180830, U10CA180886
Status last verified
May 2026
First submitted
1 Jul 2014
Last updated
17 Jun 2026
Data monitoring committee
No

Publications

  • Weiss AR, Chen YL, Scharschmidt TJ, Xue W, Gao Z, Black JO, Choy E, Davis JL, Fanburg-Smith JC, Kao SC, Kayton ML, Kessel S, Lim R, Million L, Okuno SH, Ostrenga A, Parisi MT, Pryma DA, Randall RL, Rosen MA, Shulkin BL, Terezakis S, Venkatramani R, Zambrano E, Wang D, Hawkins DS, Spunt SL. Outcomes After Preoperative Chemoradiation With or Without Pazopanib in Non-Rhabdomyosarcoma Soft Tissue Sarcoma: A Report From Children's Oncology Group and NRG Oncology. J Clin Oncol. 2023 Nov 1;41(31):4842-4848. doi: 10.1200/JCO.23.00045. Epub 2023 Jul 31.

    PubMed 37523624

  • Avutu V, Weiss AR, Reed DR, Ahmed SK, Allen-Rhoades WA, Chen YE, Davis LE, Eaton BR, Hawkins DS, Indelicato DJ, Patel SR, Randall RL, Reinke DK, Riedel RF, Scharschmidt TJ, Thornton KA, Wang D, Janeway KA, Kopp LM. Identified Enrollment Challenges of Adolescent and Young Adult Patients on the Nonchemotherapy Arm of Children's Oncology Group Study ARST1321. J Adolesc Young Adult Oncol. 2022 Jun;11(3):328-332. doi: 10.1089/jayao.2021.0103. Epub 2021 Sep 9.

    PubMed 34515544

  • Vatner R, James CD, Sathiaseelan V, Bondra KM, Kalapurakal JA, Houghton PJ. Radiation therapy and molecular-targeted agents in preclinical testing for immunotherapy, brain tumors, and sarcomas: Opportunities and challenges. Pediatr Blood Cancer. 2021 May;68 Suppl 2:e28439. doi: 10.1002/pbc.28439. Epub 2020 Aug 22.

    PubMed 32827353

  • Weiss AR, Chen YL, Scharschmidt TJ, Chi YY, Tian J, Black JO, Davis JL, Fanburg-Smith JC, Zambrano E, Anderson J, Arens R, Binitie O, Choy E, Davis JW, Hayes-Jordan A, Kao SC, Kayton ML, Kessel S, Lim R, Meyer WH, Million L, Okuno SH, Ostrenga A, Parisi MT, Pryma DA, Randall RL, Rosen MA, Schlapkohl M, Shulkin BL, Smith EA, Sorger JI, Terezakis S, Hawkins DS, Spunt SL, Wang D. Pathological response in children and adults with large unresected intermediate-grade or high-grade soft tissue sarcoma receiving preoperative chemoradiotherapy with or without pazopanib (ARST1321): a multicentre, randomised, open-label, phase 2 trial. Lancet Oncol. 2020 Aug;21(8):1110-1122. doi: 10.1016/S1470-2045(20)30325-9. Epub 2020 Jul 20.

    PubMed 32702309

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Doxorubicin, Doxorubicin Hydrochloride and Ifosfamide in people with Alveolar Soft Part Sarcoma and Angiomatoid Fibrous Histiocytoma, run by National Cancer Institute (NCI) at 381 sites in 3 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 61 inclusion and 48 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 17 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 381 sites in United States, Canada, 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 combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 9 Oct 2020). 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?

Feasible Dose: Pediatric (time frame: After the first 6 weeks of Induction). The study lists 5 primary outcomes in all. 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 NCT02180867, which also lists 4 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 17 Jun 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in