Skip to content
Triangle logo TriangleGet started
← Study library

NCT02180867 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE2, PHASE3
Status at capture
COMPLETED
Registry last update
2026-06-17

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

Feasible Dose: Pediatric

→

outcome · POSTED

Feasible Dose: Adult

→

outcome · POSTED

Percentage of Chemoradiotherapy Patients With Positive Pathologic Response at Week 13

→

outcome · POSTED

Percentage of Radiotherapy Patients With Positive Pathologic Response at Week 10

→

outcome · POSTED

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

→

outcome · POSTED

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

→

outcome · POSTED

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

→

outcome · POSTED

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

→

outcome · POSTED

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

→

outcome · NOT POSTED

Relative Frequency of Actionable Mutations

→

outcome · NOT POSTED

Prevalence of Circulating Tumor DNA (ctDNA)

→

outcome · NOT POSTED

Mean Pharmacokinetic Parameters of Doxorubicin and Pazopanib

→

outcome · NOT POSTED

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

→

outcome · NOT POSTED

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

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→
Who could take part
eligibility Criteria
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 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 * 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 Exclusion Criteria: * 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 * 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
healthy Volunteers
false
minimum Age
2 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
  3. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    See Regimen A Detailed Description.
    intervention Names
    1. Drug: Doxorubicin
    2. Drug: Doxorubicin Hydrochloride
    3. Drug: Ifosfamide
    4. Drug: Pazopanib
    5. Drug: Pazopanib Hydrochloride
    6. Radiation: Radiation Therapy
    7. Procedure: Therapeutic Conventional Surgery
    label
    Regimen A (pazopanib, chemoradiation)
    type
    EXPERIMENTAL
  2. description
    See Regimen B Detailed Description.
    intervention Names
    1. Drug: Doxorubicin
    2. Drug: Doxorubicin Hydrochloride
    3. Drug: Ifosfamide
    4. Radiation: Radiation Therapy
    5. Procedure: Therapeutic Conventional Surgery
    label
    Regimen B (chemoradiation)
    type
    EXPERIMENTAL
  3. description
    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.
    intervention Names
    1. Drug: Pazopanib
    2. Drug: Pazopanib Hydrochloride
    3. Radiation: Radiation Therapy
    4. Procedure: Therapeutic Conventional Surgery
    label
    Regimen C (pazopanib, radiation therapy)
    type
    EXPERIMENTAL
  4. description
    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.
    intervention Names
    1. Radiation: Radiation Therapy
    2. Procedure: Therapeutic Conventional Surgery
    label
    Regimen D (radiation therapy)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Regimen A (pazopanib, chemoradiation)
    2. Regimen B (chemoradiation)
    description
    Given IV
    name
    Doxorubicin
    other Names
    1. Adriablastin
    2. Hydroxydaunomycin
    3. Hydroxyl Daunorubicin
    4. Hydroxyldaunorubicin
    type
    DRUG
  2. arm Group Labels
    1. Regimen A (pazopanib, chemoradiation)
    2. Regimen B (chemoradiation)
    description
    Given IV
    name
    Doxorubicin Hydrochloride
    other Names
    1. 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)
    2. ADM
    3. Adriacin
    4. Adriamycin
    5. Adriamycin Hydrochloride
    6. Adriamycin PFS
    7. Adriamycin RDF
    8. ADRIAMYCIN, HYDROCHLORIDE
    9. Adriamycine
    10. Adriblastina
    11. Adriblastine
    12. Adrimedac
    type
    DRUG
  3. arm Group Labels
    1. Regimen A (pazopanib, chemoradiation)
    2. Regimen B (chemoradiation)
    description
    Given IV
    name
    Ifosfamide
    other Names
    1. Asta Z 4942
    2. Asta Z-4942
    3. Cyfos
    4. Holoxan
    5. Holoxane
    6. Ifex
    7. IFO
    8. IFO-Cell
    9. Ifolem
    10. Ifomida
    11. Ifomide
    12. Ifosfamidum
    type
    DRUG
  4. arm Group Labels
    1. Regimen A (pazopanib, chemoradiation)
    2. Regimen C (pazopanib, radiation therapy)
    description
    Given PO
    name
    Pazopanib
    other Names
    1. GW786034
    type
    DRUG
  5. arm Group Labels
    1. Regimen A (pazopanib, chemoradiation)
    2. Regimen C (pazopanib, radiation therapy)
    description
    Given PO
    name
    Pazopanib Hydrochloride
    other Names
    1. GW 786034B
    2. GW-786034B
    3. GW786034B
    4. Pazopater
    5. Votrient
    type
    DRUG
  6. arm Group Labels
    1. Regimen A (pazopanib, chemoradiation)
    2. Regimen B (chemoradiation)
    3. Regimen C (pazopanib, radiation therapy)
    4. Regimen D (radiation therapy)
    description
    Undergo radiation therapy
    name
    Radiation Therapy
    other Names
    1. Cancer Radiotherapy
    2. Energy Type
    3. ENERGY_TYPE
    4. Irradiate
    5. Irradiated
    6. Irradiation
    7. Radiation
    8. Radiation Therapy, NOS
    9. Radiotherapeutics
    10. Radiotherapy
    11. RT
    12. Therapy, Radiation
    type
    RADIATION
  7. arm Group Labels
    1. Regimen A (pazopanib, chemoradiation)
    2. Regimen B (chemoradiation)
    3. Regimen C (pazopanib, radiation therapy)
    4. Regimen D (radiation therapy)
    description
    Undergo surgery
    name
    Therapeutic Conventional Surgery
    type
    PROCEDURE
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
140
type
ACTUAL
Registered outcome plans (not posted results)
other Outcomes
  1. description
    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.
    measure
    Relative Frequency of Actionable Mutations
    time Frame
    At diagnosis
  2. description
    Descriptive analyses will be performed to summarize the prevalence of ctDNA.
    measure
    Prevalence of Circulating Tumor DNA (ctDNA)
    time Frame
    At diagnosis
  3. description
    Pharmacokinetic parameters such as the clearance of doxorubicin and pazopanib will be estimated.
    measure
    Mean Pharmacokinetic Parameters of Doxorubicin and Pazopanib
    time Frame
    Up to 48 hours after the end of infusion
  4. description
    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.
    measure
    Change in Fludeoxyglucose F 18 (FDG) Positron Emission Tomography (PET) Maximum Standard Uptake Value (SUVmax)
    time Frame
    From enrollment to week 10 or 13 prior to tumor resection
  5. description
    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.
    measure
    Relative Risk of Failure Based on Both Standard Imaging and Pathologic Assessment
    time Frame
    From enrollment up to 60 months
primary Outcomes
  1. description
    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.
    measure
    Feasible Dose: Pediatric
    time Frame
    After the first 6 weeks of Induction
  2. description
    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.
    measure
    Feasible Dose: Adult
    time Frame
    After the first 6 weeks of Induction
  3. description
    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.
    measure
    Percentage of Chemoradiotherapy Patients With Positive Pathologic Response at Week 13
    time Frame
    Week 13 after induction
  4. description
    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.
    measure
    Percentage of Radiotherapy Patients With Positive Pathologic Response at Week 10
    time Frame
    Week 10 after induction
  5. description
    Time to the first occurrence of relapse, progression, secondary cancer or death from any cause.
    measure
    Percentage of Radiotherapy Patients Failure Free at 5 Years Following Study Entry
    time Frame
    From enrollment to up to 60 months
secondary Outcomes
  1. description
    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.
    measure
    Percentage of Patients Local Failure Free at 5 Years Following Study Entry
    time Frame
    From enrollment to up to 60 months
  2. description
    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.
    measure
    Percentage of Patients Regional Failure Free at 5 Years Following Study Entry
    time Frame
    From enrollment to up to 60 months
  3. description
    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.
    measure
    Percentage of Patients Distant Failure Free at 5 Years Following Study Entry
    time Frame
    From enrollment to up to 60 months
  4. description
    Participants who experienced Grade 3 or higher toxicity was assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
    measure
    Percentage of Patients Who Experienced Grade 3 or Higher Toxicity 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
Full study description
brief 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.
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.
Source references
references
  1. citation
    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.
    pmid
    37523624
    type
    DERIVED
  2. citation
    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.
    pmid
    34515544
    type
    DERIVED
  3. citation
    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.
    pmid
    32827353
    type
    DERIVED
  4. citation
    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.
    pmid
    32702309
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
    1. release id
      ctgov-registry-7ad944f6deaf1f5cd6122126
      edge id
      nct-edge-72fe24aee791d9266719
      requested nct id
      NCT02180867
      primary nct id
      NCT02180867
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source file sha256
      087ef9142c0aebb539f4c900d83a659f1a22cd99367785543c73dbdf79e0b0cc
      payload sha256
      1c2900de3b9f466a8dba60c2de68be31073752ef2bfb7487deec6847f9c3c7a1
      payload
      clinical indication matching status
      not_inferred
      end exclusive
      true
      id
      nct-edge-72fe24aee791d9266719
      link basis
      explicit_NCT_identifier_in_acquired_source
      nct id
      NCT02180867
      occurrences
      1. context exact
        FNCLCC grade was strongly associated with event-free survival and overall survival.[<a href="#cit/section_3.18">18</a>] The closed COG <a href="/clinicaltrials/NCT02180867">ARST1321 (NCT02180867)</a> trial used the FNCLCC system to assign histological grade.</p> <p id="_651" tabindex="-1">The FNCLCC Sarcoma Group is descri
        end
        161086
        exact text
        NCT02180867
        start
        161075
      2. context exact
        ly associated with event-free survival and overall survival.[<a href="#cit/section_3.18">18</a>] The closed COG <a href="/clinicaltrials/NCT02180867">ARST1321 (NCT02180867)</a> trial used the FNCLCC system to assign histological grade.</p> <p id="_651" tabindex="-1">The FNCLCC Sarcoma Group is described below. The POG grad
        end
        161109
        exact text
        NCT02180867
        start
        161098
      3. context exact
        section_4.44">44</a>,<a href="#cit/section_4.45">45</a>]</p> <p id="_2868" tabindex="-1">Radiation therapy was used in the COG <a href="/clinicaltrials/NCT02180867">ARST1321</a> trial.</p> </section> </section><section id="_402"> <h3 id="_402_toc">Chemotherapy</h3> <p id="_403" tabindex="-1">The role
        end
        191063
        exact text
        NCT02180867
        start
        191052
      offset unit
      unicode_code_points
      source file
      /tmp/cancer-full-research/nci/raw/a528455ae29adeef13.html
      source file sha256
      087ef9142c0aebb539f4c900d83a659f1a22cd99367785543c73dbdf79e0b0cc
      source json pointer
      Source null
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source retrieved at
      2026-09-09T23:22:19.581631+00:00
      source string basis
      UTF-8_text_with_universal_newline_translation
      source string sha256
      c913a60878c18e616f39a4e354327dd9ca49d6f2b8e7e636a26ce81aa9170d23
      source title
      Childhood Soft Tissue Sarcoma Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: April 21, 2025
        datetime
        2025-04-21T12:00:00Z
        display
        April 21, 2025

    Preserved source evidence · Not medical advice