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

Completed · Phase 2/Phase 3

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

In brief

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.

Key facts

Study ID

NCT02180867

Run by

National Cancer Institute (NCI)

People needed

140

Starts

2014-08-12

Expected to finish

2026-03-31

Last updated by the study team

2026-06-17

Who can join

Age: 2 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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

You may not qualify if…

• 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

Where it is running

• University of Alabama at Birmingham Cancer Center — Birmingham, Alabama, United States
• The Kirklin Clinic at Acton Road — Birmingham, Alabama, United States
• Anchorage Associates in Radiation Medicine — Anchorage, Alaska, United States
• Alaska Breast Care and Surgery LLC — Anchorage, Alaska, United States
• Alaska Oncology and Hematology LLC — Anchorage, Alaska, United States
• Alaska Women's Cancer Care — Anchorage, Alaska, United States
• Anchorage Oncology Centre — Anchorage, Alaska, United States
• Katmai Oncology Group — Anchorage, Alaska, United States
• Providence Alaska Medical Center — Anchorage, Alaska, United States
• Banner Children's at Desert — Mesa, Arizona, United States
• Phoenix Childrens Hospital — Phoenix, Arizona, United States
• Banner University Medical Center - Tucson — Tucson, Arizona, United States
• Arkansas Children's Hospital — Little Rock, Arkansas, United States
• Kaiser Permanente-Anaheim — Anaheim, California, United States
• AIS Cancer Center at San Joaquin Community Hospital — Bakersfield, California, United States
• Providence Saint Joseph Medical Center/Disney Family Cancer Center — Burbank, California, United States
• Kaiser Permanente Downey Medical Center — Downey, California, United States
• City of Hope Comprehensive Cancer Center — Duarte, California, United States
• Loma Linda University Medical Center — Loma Linda, California, United States
• Miller Children's and Women's Hospital Long Beach — Long Beach, California, United States
• Children's Hospital Los Angeles — Los Angeles, California, United States
• Kaiser Permanente Los Angeles Medical Center — Los Angeles, California, United States
• Los Angeles General Medical Center — Los Angeles, California, United States
• USC / Norris Comprehensive Cancer Center — Los Angeles, California, United States
• Children's Hospital of Alabama — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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