NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)

Inclusion Criteria: Inclusion Criteria - All Patients * Patients must be 1-30 years at the time of the biopsy that established the diagnosis of NRSTS. * Surgical Resection: Patients who had an upfront resection prior to enrollment will be eligible if they are able to begin therapy within 28 days of resection assuming other eligibility criteria are met. Delayed resection is preferred for all patients with intermediate and high-risk disease. * Lansky performance status score ≥ 60 for patients ≤ 16 years of age. Karnofsky performance status score ≥ 60 for patients \>16 years of age. Note patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. Diagnosis • Patients with CIC-DUX 4 rearranged sarcomas will be enrolled on the high-risk stratum only, regardless of presence of metastasis, size, or resection status. Patient has low-risk disease if the patient has a: * Low-grade tumor of any size where R0 or R1 surgical margins are anticipated or achieved. * High-grade tumors that are \< 5 cm where R0 or R1 resection margins are anticipated or achieved. Patient must have adequate organ function in the organs that will be within the radiotherapy field. Adequate renal function defined as: * Creatinine clearance or radioisotope GFR \> 70 mL/min/1.73 m2, or * A normal serum creatinine based on age/gender as follows Age Maximum Serum Creatinine (mg/dL) Male Female 2 to \< 6 years 0.8 0.8 6 to \< 10 years 1 1 10 to \< 13 years 1.2 1.2 13 to \< 16 years 1.5 1.4 \> 16 years 1.5 1.4 Adequate liver function defined as: * Total bilirubin \< 1.5 x upper limit of normal (ULN) for age * SGOT (AST) or SGPT (ALT) \< 2.5 x ULN for age Adequate cardiac function defined as: * Ejection fraction of \> 55% by echocardiogram or cardiac MRI * QTc \< 480 msec Adequate pulmonary function defined as: * 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. Inclusion Criteria - Intermediate and High Risk Participants Patient has intermediate-risk if the patient has a: * Low-grade non-metastatic initially unresectable disease at study enrollment where delayed resection is planned. * High-grade \< 5 cm non-metastatic initially unresectable disease at study enrollment where delayed resection is planned. Of note, patients enrolled on the low-risk arm who were unable to achieve gross total resection where delayed re-resection is planned are eligible for this arm. * High-grade tumor \> 5 cm that is potentially resectable. Patient high-risk if the patient has: * Metastatic disease at presentation * Unresectable disease at study enrollment where delayed resection is not anticipated. Of note, patients enrolled on the low-risk arm who were unable to achieve gross total resection where delayed re-resection is not-planned are eligible for this arm. * CIC-DUX4 rearranged sarcoma Organ Function Adequate bone marrow function defined as: * Absolute neutrophil count \> 1000/µL * Platelet count \> 100,000/µL * Hemoglobin \> 8 g/dL for patients \< 16 years of age * Hemoglobin \> 9 g/dL for patients \> 16 years of age Note: No transfusions are permitted 7 days prior to laboratory studies to determine eligibility. Adequate renal function defined as: * Creatinine clearance or radioisotope GFR \> 70 mL/min/1.73 m2, or * A normal serum creatinine based on age/gender as follows Age Maximum Serum Creatinine (mg/dL) Male Female 2 to \< 6 years 0.8 0.8 6 to \< 10 years 1 1 10 to \< 13 years 1.2 1.2 13 to \< 16 years 1.5 1.4 \> 16 years 1.5 1.4 Adequate liver function defined as: * Total bilirubin \< 1.5 x upper limit of normal (ULN) for age * SGOT (AST) or SGPT (ALT) \< 2.5 x ULN for age Adequate cardiac function defined as: * Ejection fraction of \> 55% by echocardiogram or cardiac MRI * QTc \< 480 msec Adequate pulmonary function defined as: * 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. Anticoagulation Patients on low molecular weight heparin, warfarin (with a stable INR), or direct oral anticoagulants (DOAC) who have been on a stable dose of are eligible. Patients being treated for a pulmonary embolism or deep venous thrombosis (DVT) must have been treated for a minimum of 6 weeks prior to starting therapy treatment. Life Expectancy Patient must have a life expectancy of at least 3 months with appropriate therapy. Exclusion Criteria: * Patients with known primary CNS sarcoma or CNS metastases are not eligible. Note: Brain imaging is not an eligibility requirement. Tumors with intracranial extension will be allowed. * Patients with the following histologic diagnosis are not eligible: intermediate locally aggressive tumors as defined by WHO, malignant rhabdoid tumor, alveolar soft part sarcoma, infantile fibrosarcoma, unresectable/metastatic dermatofibrosarcoma protuberans, inflammatory myofibroblastic tumor, desmoid fibromatosis, rhabdomyosarcoma, desmoplastic small round cell tumor, BCOR-CCNB3 fusion positive sarcoma. * Bleeding diathesis: 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). * Uncontrolled hypertension: Patients with uncontrolled hypertension (CTCAE v5 Grade ≥ 2) are ineligible. Hypertension must be well controlled on stable doses of medication for at least two weeks. Prior Therapy * Patients must have had no prior systemic therapy for the treatment of the NRSTS * Patients must have had no prior anthracycline or ifosfamide chemotherapy * Patients must have had no prior use of pazopanib or similar multi-targeted TKI. Patients must have had no prior radiotherapy to tumor-involved sites. Note: Patients previously treated for a non-NRSTS cancer ar