ClinicalTrials.gg
Sign In
CompletedNCT02180867Updated Jun 17, 2026Results posted

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 interventional study of Doxorubicin and Doxorubicin Hydrochloride in Alveolar Soft Part Sarcoma, Angiomatoid Fibrous Histiocytoma and Atypical Fibroxanthoma, sponsored by National Cancer Institute (NCI). Completed at 381 sites in 3 countries. Open to participants aged 2 Years and older. Per ClinicalTrials.gov, last updated 2026-06-17.

Sponsored by National Cancer Institute (NCI) · Phase 2/3, Interventional, and Treatment

Phase
Phase 2/3
Study type
Interventional
Enrollment
140
Allocation
Randomized
Ages
2 Years and older
Sex
All
01

Study 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. 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:

I. 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:

I. 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:

I. 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.

V. 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.

02

Conditions studied

  • Alveolar Soft Part Sarcoma
  • Angiomatoid Fibrous Histiocytoma
  • Atypical Fibroxanthoma
  • Clear Cell Sarcoma of Soft Tissue
  • Epithelioid Malignant Peripheral Nerve Sheath Tumor
  • Epithelioid Sarcoma
  • Extraskeletal Myxoid Chondrosarcoma
  • Extraskeletal Osteosarcoma
  • Fibrohistiocytic Neoplasm
  • Fibrosarcoma
  • Inflammatory Myofibroblastic Tumor
  • Intimal Sarcoma
  • Leiomyosarcoma
  • Liposarcoma
  • Liver Embryonal Sarcoma
  • Low Grade Fibromyxoid Sarcoma
  • Low Grade Myofibroblastic Sarcoma
  • Malignant Peripheral Nerve Sheath Tumor
  • Malignant Skin Granular Cell Tumor
  • Malignant Triton Tumor
  • Mesenchymal Chondrosarcoma
  • Myxofibrosarcoma
  • Myxoid Chondrosarcoma
  • Myxoinflammatory Fibroblastic Sarcoma
  • Nerve Sheath Neoplasm
  • PEComa
  • Pericytic Neoplasm
  • Plexiform Fibrohistiocytic Tumor
  • Sclerosing Epithelioid Fibrosarcoma
  • Skin Glomus Tumor
  • Stage IB Soft Tissue Sarcoma AJCC v7
  • Stage IIB Soft Tissue Sarcoma AJCC v7
  • Stage III Soft Tissue Sarcoma AJCC v7
  • Stage IV Soft Tissue Sarcoma AJCC v7
  • Synovial Sarcoma
  • Undifferentiated High Grade Pleomorphic Sarcoma of Bone
03

In context

Sarcoma, Alveolar Soft Part

51 studies on the registry are indexed under Sarcoma, Alveolar Soft Part; 10 are open to participants now.

This study's enrollment of 140 is above the median of 53 across 49 interventional studies indexed under Sarcoma, Alveolar Soft Part.

Browse Sarcoma, Alveolar Soft Part studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,556 studies on the registry; 336 are open to participants now.

Of its 411 completed or terminated interventional studies of FDA-regulated products, 373 (91%) have results posted.

Browse National Cancer Institute (NCI) studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
2 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • 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 disease to warrant chemotherapy based on size and grade and
    • Medically deemed able or unable to undergo chemotherapy
    • Notes: an incisional or core biopsy is preferred; fine needle aspiration biopsy is not acceptable to establish the diagnosis

  • 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
  • performance status score >= 70 for patients > 16 years of age
  • >= 1500/uL; Note: no transfusions are permitted 7 days prior to laboratory studies to determine eligibility
  • count >= 100,000/uL; Note: no transfusions are permitted 7 days prior to laboratory studies to determine eligibility
  • >= 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

  • or radioisotope (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 =\< 1.5 x (ULN) for age
  • Serum glutamic oxaloacetic transaminase () (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 of >= 50% by radionuclide angiogram
  • 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 [INR]) are eligible
  • Patient must have a of at least 3 months with appropriate therapy
  • All patients and/or their parents or legal guardians must sign a written
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion criteria

Exclusion Criteria:

  • Patients with grade 1 NRSTS tumors of any size are not eligible
  • Patients with known central nervous system (CNS) 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
    • 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 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 () 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 )
  • Certain medications that are associated with a risk for 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/ 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 (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 (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
  • (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 are not eligible unless a negative pregnancy test result has been obtained
  • Unwillingness to use an effective method for the duration of their study participation and for at least 1 month after treatment is completed if sexually active with
Terms in these criteria, in plain language(26)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Metastases

Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.

Biopsy and archival tissue

A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.

Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.

Karnofsky performance status (KPS)

A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.

Studies often ask for 60 or 70 and above. Your doctor gives the score.

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

Creatinine clearance (CrCl)

How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.

GFR and eGFR (kidney filtering)

GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².

Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

LVEF (left ventricular ejection fraction)

The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.

QT and QTc

On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.

The study may name a correction formula and a limit in milliseconds, often around 450–480.

INR, PT and aPTT (clotting tests)

Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.

Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.

Life expectancy

The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

CYP3A (CYP3A4) inhibitors and inducers

CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.

Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

TIA (transient ischaemic attack)

A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.

Stroke symptoms need emergency care at once, even if they go away.

NYHA class (heart failure)

The New York Heart Association’s four classes of how much heart failure limits physical activity.

I
No limits: ordinary activity causes no undue tiredness or breathlessness.
II
Slight limits: comfortable at rest, ordinary activity causes symptoms.
III
Marked limits: comfortable at rest, less than ordinary activity causes symptoms.
IV
Symptoms even at rest; any activity makes them worse.

Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Reproductive potential

Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.

Criteria about it usually ask for contraception during the study and for a time after it.

05

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
140 participants (actual)

Study arms

  • Experimental
    Regimen A (pazopanib, chemoradiation)

    See Regimen A Detailed Description.

    Drug: Doxorubicin · Drug: Doxorubicin Hydrochloride · Drug: Ifosfamide · Drug: Pazopanib · Drug: Pazopanib Hydrochloride · Radiation: Radiation Therapy · Procedure: Therapeutic Conventional Surgery

  • Experimental
    Regimen B (chemoradiation)

    See Regimen B Detailed Description.

    Drug: Doxorubicin · Drug: Doxorubicin Hydrochloride · Drug: Ifosfamide · Radiation: Radiation Therapy · Procedure: Therapeutic Conventional Surgery

  • Experimental
    Regimen C (pazopanib, radiation therapy)

    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.

    Drug: Pazopanib · Drug: Pazopanib Hydrochloride · Radiation: Radiation Therapy · Procedure: Therapeutic Conventional Surgery

  • Experimental
    Regimen D (radiation therapy)

    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.

    Radiation: Radiation Therapy · Procedure: Therapeutic Conventional Surgery

Interventions

  • DrugDoxorubicin

    Given IV

    Also known as: Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin

  • DrugDoxorubicin Hydrochloride

    Given IV

    Also known as: 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, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin HCl, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, FI106, hydroxydaunorubicin, Rubex

  • DrugIfosfamide

    Given IV

    Also known as: Asta Z 4942, Asta Z-4942, Cyfos, Holoxan, Holoxane, Ifex, IFO, IFO-Cell, Ifolem, Ifomida, Ifomide, Ifosfamidum, Ifoxan, IFX, Iphosphamid, Iphosphamide, Iso-Endoxan, Isoendoxan, Isophosphamide, Mitoxana, MJF 9325, MJF-9325, Naxamide, Seromida, Tronoxal, Z 4942, Z-4942

  • DrugPazopanib

    Given PO

    Also known as: GW786034

  • DrugPazopanib Hydrochloride

    Given PO

    Also known as: GW 786034B, GW-786034B, GW786034B, Pazopater, Votrient

  • RadiationRadiation Therapy

    Undergo radiation therapy

    Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

  • ProcedureTherapeutic Conventional Surgery

    Undergo surgery

06

What researchers measure

Primary outcomes

  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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: From enrollment to up to 60 months

Secondary outcomes

  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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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).

    Time frame: 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

Other outcomes

  1. Relative Frequency of Actionable Mutations

    Descriptive statistical analyses will be provided to estimate the relative frequency of actionable mutations across the whole cohort and within more common histological subtypes, like synovial sarcoma and malignant peripheral nerve sheath tumors.

    Time frame: At diagnosis

  2. Prevalence of Circulating Tumor DNA (ctDNA)

    Descriptive analyses will be performed to summarize the prevalence of ctDNA.

    Time frame: At diagnosis

  3. Mean Pharmacokinetic Parameters of Doxorubicin and Pazopanib

    Pharmacokinetic parameters such as the clearance of doxorubicin and pazopanib will be estimated.

    Time frame: Up to 48 hours after the end of infusion

  4. Change in Fludeoxyglucose F 18 (FDG) Positron Emission Tomography (PET) Maximum Standard Uptake Value (SUVmax)

    To evaluate change in FDG 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.

    Time frame: From enrollment to week 10 or 13 prior to tumor resection

  5. Relative Risk of Failure Based on Both Standard Imaging and Pathologic Assessment

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

    Time frame: From enrollment up to 60 months

07

Results

Posted Oct 9, 2020

Participant flow

Participant flow — Overall Study
MilestoneDose-Finding Level 1 CRDose-Finding Level 1 RTDose-Finding Level 2 RTRegimen ARegimen BRegimen CRegimen D
Started101110494866
Pediatric patients643181910
Adult patients477312956
Completed406232131
Not completed6114262735
Withdrew: Adverse event3415000
Withdrew: Death0000100
Withdrew: Lack of efficacy0201601
Withdrew: Physician decision13110934
Withdrew: Withdrawal by subject0001100
Withdrew: Ineligible1203500
Withdrew: Repeat eligibility studies0000100
Withdrew: Refusal of further protocol therapy1026400

Outcome measures

PrimaryFeasible 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.

Time frame:
After the first 6 weeks of Induction
Reported as:
Number · milligram per square meter
Feasible Dose: Pediatric
milligram per square meterAll Pediatric Dose Finding CR CohortsAll Pediatric Dose Finding RT Cohorts
Feasible Dose: Pediatric350450
PrimaryFeasible 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.

Time frame:
After the first 6 weeks of Induction
Reported as:
Number · milligram
Feasible Dose: Adult
milligramAll Adult Dose Finding CR CohortsAll Adult Dose Finding RT Cohorts
Feasible Dose: Adult600800
PrimaryPercentage 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.

Time frame:
Week 13 after induction
Reported as:
Number · Percentage of patients
Percentage of Chemoradiotherapy Patients With Positive Pathologic Response at Week 13
Percentage of patientsDose-Finding Level 1 CRRegimen ARegimen B
Percentage of Chemoradiotherapy Patients With Positive Pathologic Response at Week 1366.67 (28.95 to 100)46.67 (28.81 to 64.52)24 (7.26 to 40.74)
PrimaryPercentage 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.

Time frame:
Week 10 after induction
Reported as:
Number · Percentage of patients
Percentage of Radiotherapy Patients With Positive Pathologic Response at Week 10
Percentage of patientsDose-Finding Level 1 RTDose-Finding Level 2 RTRegimen CRegimen D
Percentage of Radiotherapy Patients With Positive Pathologic Response at Week 100 (0 to 0)40 (0 to 82.94)0 (0 to 0)0 (0 to 0)
PrimaryPercentage 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.

Time frame:
From enrollment to up to 60 months

No measurements were reported for this outcome.

SecondaryPercentage 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.

Time frame:
From enrollment to up to 60 months
Reported as:
Number · percentage of participants
Percentage of Patients Local Failure Free at 5 Years Following Study Entry
percentage of participantsDose-Finding Level 1 CRDose-Finding Level 1 RTDose-Finding Level 2 RTRegimen ARegimen BRegimen CRegimen D
Percentage of Patients Local Failure Free at 5 Years Following Study Entry100.00 (100.00 to 100.00)80.00 (30.42 to 100.00)100.00 (100.00 to 100.00)91.09 (77.33 to 100.00)87.32 (68.05 to 100.00)100.00 (100.00 to 100.00)83.33 (16.65 to 100.00)
SecondaryPercentage 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.

Time frame:
From enrollment to up to 60 months
Reported as:
Number · percentage of participants
Percentage of Patients Regional Failure Free at 5 Years Following Study Entry
percentage of participantsDose-Finding Level 1 CRDose-Finding Level 1 RTDose-Finding Level 2 RTRegimen ARegimen BRegimen CRegimen D
Percentage of Patients Regional Failure Free at 5 Years Following Study Entry100.00 (100.00 to 100.00)100.00 (100.00 to 100.00)100.00 (100.00 to 100.00)100.00 (100.00 to 100.00)100.00 (100.00 to 100.00)100.00 (100.00 to 100.00)100.00 (100.00 to 100.00)
SecondaryPercentage 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.

Time frame:
From enrollment to up to 60 months
Reported as:
Number · percentage of participants
Percentage of Patients Distant Failure Free at 5 Years Following Study Entry
percentage of participantsDose-Finding Level 1 CRDose-Finding Level 1 RTDose-Finding Level 2 RTRegimen ARegimen BRegimen CRegimen D
Percentage of Patients Distant Failure Free at 5 Years Following Study Entry77.78 (48.44 to 100.00)33.33 (0.00 to 71.05)70.00 (32.43 to 100.00)59.89 (39.11 to 78.67)62.62 (39.99 to 85.24)80.00 (39.52 to 100.00)66.67 (0.00 to 100.00)
SecondaryPercentage 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).

Time frame:
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
Reported as:
Number · Percentage of patients
Percentage of Patients Who Experienced Grade 3 or Higher Toxicity Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
Percentage of patientsDose-Finding Level 1 CRDose-Finding Level 1 RTDose-Finding Level 2 RTRegimen ARegimen BRegimen CRegimen D
Pediatric Patients60 (17.06 to 100)66.67 (13.32 to 100)33.33 (0 to 86.68)75 (53.78 to 96.22)33.33 (11.56 to 55.11)0 (0 to 0)—
Adult Patients75 (32.56 to 100)66.67 (28.95 to 100)57.14 (20.48 to 93.80)86.67 (74.50 to 98.83)36 (17.18 to 54.82)40 (0 to 82.94)0 (0 to 0)
Other pre-specifiedRelative Frequency of Actionable Mutations

Descriptive statistical analyses will be provided to estimate the relative frequency of actionable mutations across the whole cohort and within more common histological subtypes, like synovial sarcoma and malignant peripheral nerve sheath tumors.

Time frame:
At diagnosis

Results for this outcome have not been posted.

Other pre-specifiedPrevalence of Circulating Tumor DNA (ctDNA)

Descriptive analyses will be performed to summarize the prevalence of ctDNA.

Time frame:
At diagnosis

Results for this outcome have not been posted.

Other pre-specifiedMean Pharmacokinetic Parameters of Doxorubicin and Pazopanib

Pharmacokinetic parameters such as the clearance of doxorubicin and pazopanib will be estimated.

Time frame:
Up to 48 hours after the end of infusion

Results for this outcome have not been posted.

Other pre-specifiedChange in Fludeoxyglucose F 18 (FDG) Positron Emission Tomography (PET) Maximum Standard Uptake Value (SUVmax)

To evaluate change in FDG 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.

Time frame:
From enrollment to week 10 or 13 prior to tumor resection

Results for this outcome have not been posted.

Other pre-specifiedRelative Risk of Failure Based on Both Standard Imaging and Pathologic Assessment

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

Time frame:
From enrollment up to 60 months

Results for this outcome have not been posted.

Adverse events

Collected over 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. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Dose-Finding Level 1 CR1/9 (11.1%)6/9 (66.7%)4/9 (44.4%)
Dose-Finding Level 1 RT4/9 (44.4%)6/9 (66.7%)2/9 (22.2%)
Dose-Finding Level 2 RT3/10 (30%)2/10 (20%)5/10 (50%)
Regimen A5/46 (10.9%)33/46 (71.7%)20/46 (43.5%)
Regimen B9/43 (20.9%)8/43 (18.6%)10/43 (23.3%)
Regimen C0/6 (0%)1/6 (16.7%)1/6 (16.7%)
Regimen D2/6 (33.3%)0/6 (0%)0/6 (0%)
Most frequent serious events
Showing 10 of 87
Most frequent serious events
EventDose-Finding Level 1 CRDose-Finding Level 1 RTDose-Finding Level 2 RTRegimen ARegimen BRegimen CRegimen D
Wound dehiscenceInjury, poisoning and procedural complications2/40/60/74/300/250/50/6
Wound infectionInfections and infestations1/43/61/71/301/250/50/6
Febrile neutropeniaBlood and lymphatic system disorders1/50/30/37/160/180/1—
Febrile neutropeniaBlood and lymphatic system disorders1/40/60/711/301/250/50/6
Creatinine increasedInvestigations0/51/30/30/160/180/1—
DiarrheaGastrointestinal disorders0/50/31/30/160/180/1—
HyperkalemiaMetabolism and nutrition disorders0/50/31/30/160/180/1—
Wound dehiscenceInjury, poisoning and procedural complications0/51/30/31/161/180/1—
Wound infectionInfections and infestations0/51/30/31/160/180/1—
Acute kidney injuryRenal and urinary disorders0/51/30/30/160/180/1—
Most frequent other events
Showing 10 of 32
Most frequent other events
EventDose-Finding Level 1 CRDose-Finding Level 1 RTDose-Finding Level 2 RTRegimen ARegimen BRegimen CRegimen D
Neutrophil count decreasedInvestigations1/40/60/710/302/250/50/6
Wound dehiscenceInjury, poisoning and procedural complications0/40/62/70/300/250/50/6
Neutrophil count decreasedInvestigations1/50/30/34/165/180/1—
White blood cell decreasedInvestigations1/50/30/34/163/180/1—
Lymphocyte count decreasedInvestigations1/40/61/72/303/250/50/6
White blood cell decreasedInvestigations1/40/60/76/302/250/50/6
Alanine aminotransferase increasedInvestigations1/50/30/31/160/180/1—
HypertensionVascular disorders1/50/30/30/160/180/1—
Lymphocyte count decreasedInvestigations1/50/30/33/162/180/1—
Wound complicationInjury, poisoning and procedural complications1/50/30/30/160/180/1—

Baseline characteristics

It was pre-specified to combine adult and pediatric participants for analysis as they received an equivalent dose of Pazopanib. There were no patients enrolled onto Dose-Finding Level 0 CR and Dose-Finding Level 2 CR or Dose-Finding Level 0 RT.

Age, Continuous
Age, Continuous(Months)Dose-Finding Level 1 CRDose-Finding Level 1 RTDose-Finding Level 2 RTRegimen ARegimen BRegimen CRegimen DTotal
Mean225.1 ± 57.8524.3 ± 270.3407.3 ± 224.7376.3 ± 243.4356.2 ± 221.8547.2 ± 260.6722.8 ± 141.9394.6 ± 242.3
Sex: Female, Male
Sex: Female, Male(Participants)Dose-Finding Level 1 CRDose-Finding Level 1 RTDose-Finding Level 2 RTRegimen ARegimen BRegimen CRegimen DTotal
Female43330182363
Male68719304377
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Dose-Finding Level 1 CRDose-Finding Level 1 RTDose-Finding Level 2 RTRegimen ARegimen BRegimen CRegimen DTotal
Hispanic or Latino2111390026
Not Hispanic or Latino699343866108
Unknown or Not Reported21021006
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Dose-Finding Level 1 CRDose-Finding Level 1 RTDose-Finding Level 2 RTRegimen ARegimen BRegimen CRegimen DTotal
American Indian or Alaska Native00000000
Asian00001001
Native Hawaiian or Other Pacific Islander00000000
Black or African American221361015
White788393855110
More than one race00000000
Unknown or Not Reported111730114
08

Study locations

381 sites
  • Children's Hospital of Alabama
    Birmingham, Alabama 35233, United States
  • University of Alabama at Birmingham Cancer Center
    Birmingham, Alabama 35233, United States
  • The Kirklin Clinic at Acton Road
    Birmingham, Alabama 35243, United States
  • Anchorage Associates in Radiation Medicine
    Anchorage, Alaska 98508, United States
  • Alaska Breast Care and Surgery LLC
    Anchorage, Alaska 99508, United States
  • Alaska Oncology and Hematology LLC
    Anchorage, Alaska 99508, United States
  • Alaska Women's Cancer Care
    Anchorage, Alaska 99508, United States
  • Anchorage Oncology Centre
    Anchorage, Alaska 99508, United States
  • Katmai Oncology Group
    Anchorage, Alaska 99508, United States
  • Providence Alaska Medical Center
    Anchorage, Alaska 99508, United States
  • Banner Children's at Desert
    Mesa, Arizona 85202, United States
  • Phoenix Childrens Hospital
    Phoenix, Arizona 85016, United States
  • Banner University Medical Center - Tucson
    Tucson, Arizona 85719, United States
  • Arkansas Children's Hospital
    Little Rock, Arkansas 72202-3591, United States
  • Kaiser Permanente-Anaheim
    Anaheim, California 92806, United States
  • AIS Cancer Center at San Joaquin Community Hospital
    Bakersfield, California 93301, United States
  • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    Burbank, California 91505, United States
  • Kaiser Permanente Downey Medical Center
    Downey, California 90242, United States
  • City of Hope Comprehensive Cancer Center
    Duarte, California 91010, United States
  • Loma Linda University Medical Center
    Loma Linda, California 92354, United States
  • Miller Children's and Women's Hospital Long Beach
    Long Beach, California 90806, United States
  • Children's Hospital Los Angeles
    Los Angeles, California 90027, United States
  • Kaiser Permanente Los Angeles Medical Center
    Los Angeles, California 90027, United States
  • Los Angeles General Medical Center
    Los Angeles, California 90033, United States
  • USC / Norris Comprehensive Cancer Center
    Los Angeles, California 90033, United States
  • Cedars-Sinai Medical Center
    Los Angeles, California 90048, United States
  • UCLA / Jonsson Comprehensive Cancer Center
    Los Angeles, California 90095, United States
  • Valley Children's Hospital
    Madera, California 93636, United States
  • UCSF Benioff Children's Hospital Oakland
    Oakland, California 94609, United States
  • Kaiser Permanente-Oakland
    Oakland, California 94611, United States
  • Children's Hospital of Orange County
    Orange, California 92868, United States
  • Lucile Packard Children's Hospital Stanford University
    Palo Alto, California 94304, United States
  • Stanford Cancer Institute Palo Alto
    Palo Alto, California 94304, United States
  • Kaiser Permanente-Riverside
    Riverside, California 92505, United States
  • Sutter Medical Center Sacramento
    Sacramento, California 95816, United States
  • University of California Davis Comprehensive Cancer Center
    Sacramento, California 95817, United States
  • Kaiser Permanente-San Diego Zion
    San Diego, California 92120, United States
  • Rady Children's Hospital - San Diego
    San Diego, California 92123, United States
  • UCSF Medical Center-Mission Bay
    San Francisco, California 94158, United States
  • Kaiser Permanente-San Marcos
    San Marcos, California 92078, United States
  • Kaiser San Rafael-Gallinas
    San Rafael, California 94903, United States
  • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
    Torrance, California 90502, United States
  • Gene Upshaw Memorial Tahoe Forest Cancer Center
    Truckee, California 96161, United States
  • Children's Hospital Colorado
    Aurora, Colorado 80045, United States
  • UCHealth University of Colorado Hospital
    Aurora, Colorado 80045, United States
  • UCHealth Memorial Hospital Central
    Colorado Springs, Colorado 80909, United States
  • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
    Denver, Colorado 80218, United States
  • Poudre Valley Hospital
    Fort Collins, Colorado 80524, United States
  • Connecticut Children's Medical Center
    Hartford, Connecticut 06106, United States
  • Yale University
    New Haven, Connecticut 06520, United States
  • Alfred I duPont Hospital for Children
    Wilmington, Delaware 19803, United States
  • MedStar Georgetown University Hospital
    Washington D.C., District of Columbia 20007, United States
  • Children's National Medical Center
    Washington D.C., District of Columbia 20010, United States
  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
    Deerfield Beach, Florida 33442, United States
  • Golisano Children's Hospital of Southwest Florida
    Fort Myers, Florida 33908, United States
  • UF Health Cancer Institute - Gainesville
    Gainesville, Florida 32610, United States
  • Memorial Regional Hospital/Joe DiMaggio Children's Hospital
    Hollywood, Florida 33021, United States
  • Nemours Children's Clinic-Jacksonville
    Jacksonville, Florida 32207, United States
  • University of Miami Miller School of Medicine-Sylvester Cancer Center
    Miami, Florida 33136, United States
  • Nicklaus Children's Hospital
    Miami, Florida 33155, United States
  • AdventHealth Orlando
    Orlando, Florida 32803, United States
  • Nemours Children's Hospital
    Orlando, Florida 32827, United States
  • Nemours Children's Clinic - Pensacola
    Pensacola, Florida 32504, United States
  • Johns Hopkins All Children's Hospital
    St. Petersburg, Florida 33701, United States
  • Saint Joseph's Hospital/Children's Hospital-Tampa
    Tampa, Florida 33607, United States
  • Moffitt Cancer Center
    Tampa, Florida 33612, United States
  • Saint Mary's Medical Center
    West Palm Beach, Florida 33407, United States
  • Emory University Hospital Midtown
    Atlanta, Georgia 30308, United States
  • Emory University Hospital/Winship Cancer Institute
    Atlanta, Georgia 30322, United States
  • Children's Healthcare of Atlanta - Arthur M Blank Hospital
    Atlanta, Georgia 30329, United States
  • Augusta University Medical Center
    Augusta, Georgia 30912, United States
  • Memorial Health University Medical Center
    Savannah, Georgia 31404, United States
  • Straub Clinic and Hospital
    Honolulu, Hawaii 96813, United States
  • Kaiser Permanente Moanalua Medical Center
    Honolulu, Hawaii 96819, United States
  • Kapiolani Medical Center for Women and Children
    Honolulu, Hawaii 96826, United States
  • Saint Luke's Cancer Institute - Boise
    Boise, Idaho 83712, United States
  • Saint Luke's Cancer Institute - Fruitland
    Fruitland, Idaho 83619, United States
  • Saint Luke's Cancer Institute - Meridian
    Meridian, Idaho 83642, United States
  • Saint Luke's Cancer Institute - Nampa
    Nampa, Idaho 83687, United States
  • Saint Luke's Cancer Institute - Twin Falls
    Twin Falls, Idaho 83301, United States
  • Lurie Children's Hospital-Chicago
    Chicago, Illinois 60611, United States
  • Northwestern University
    Chicago, Illinois 60611, United States
  • Rush MD Anderson Cancer Center
    Chicago, Illinois 60612, United States
  • University of Illinois
    Chicago, Illinois 60612, United States
  • University of Chicago Comprehensive Cancer Center
    Chicago, Illinois 60637, United States
  • Northwestern Medicine Cancer Center Delnor
    Geneva, Illinois 60134, United States
  • Loyola University Medical Center
    Maywood, Illinois 60153, United States
  • SSM Health Good Samaritan
    Mount Vernon, Illinois 62864, United States
  • UC Comprehensive Cancer Center at Silver Cross
    New Lenox, Illinois 60451, United States
  • Advocate Children's Hospital-Oak Lawn
    Oak Lawn, Illinois 60453, United States
  • Advocate Children's Hospital-Park Ridge
    Park Ridge, Illinois 60068, United States
  • OSF Children's Hospital of Illinois
    Peoria, Illinois 61637, United States
  • Saint John's Hospital
    Springfield, Illinois 62702, United States
  • Southern Illinois University School of Medicine
    Springfield, Illinois 62702, United States
  • Springfield Memorial Hospital
    Springfield, Illinois 62781, United States
  • Northwestern Medicine Cancer Center Warrenville
    Warrenville, Illinois 60555, United States
  • Riley Hospital for Children
    Indianapolis, Indiana 46202, United States
  • Ascension Saint Vincent Indianapolis Hospital
    Indianapolis, Indiana 46260, United States
  • Reid Health
    Richmond, Indiana 47374, United States
  • Blank Children's Hospital
    Des Moines, Iowa 50309, United States

Showing the first 100 of 381 sites across 3 countries. Choose a country and city above to see the rest.

09

References and documents

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 ↗

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Aug 2014 to primary completion in Jun 2019, 58 months.

Results were first posted in Oct 2020, 1 year 3 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Jul 1, 2014
First posted
Jul 3, 2014
StartActual
Aug 12, 2014
Primary completionActual
Jun 30, 2019
CompletionActual
Mar 31, 2026
Results first posted
Oct 9, 2020
Last update
Jun 17, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Jun 17, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02180867
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Jul 3, 2014
Start date
Aug 12, 2014
Primary completion
Jun 30, 2019
Completion
Mar 31, 2026
Results posted
Oct 9, 2020
Last update
Jun 17, 2026

Study contacts

Aaron R Weiss
principal investigator · Children's Oncology Group

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in May 2026. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drugs tested here: Doxorubicin · Ifosfamide · Pazopanib

Other studies in this condition

Sarcoma, Alveolar Soft Part →

Other studies from this sponsor

National Cancer Institute (NCI) →

Start the discussion