Pazopanib in Combination with Trabectedin, Ipilimumab and Nivolumab for the Treatment of Pediatric and Young Adults with Recurrent and Refractory Soft Tissue Sarcoma

Inclusion Criteria

• Patients must be > 1 year of age and ≤ 30 years of age at time of initiation of protocol therapy
• Patients have a histologically or radiographically confirmed relapsed or refractory STS
• Patients must have evaluable disease * Patients may have central nervous system (CNS) metastases at study entry, if they are previously treated or stable (defined by not requiring initiation or the need for increased steroids for 7 days)
• Karnofsky ≥ 50% for patients > 16 years old, and Lansky ≥ 50 for patients 1-16 years old
• Patients may have received prior therapy including single-agent pazopanib or trabectedin. Patients may not have previously been treated with combination therapy of pazopanib and trabectedin * Patients must be fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. Delayed toxicities from chemotherapy (e.g. requiring electrolyte replacement, alopecia) will be permitted as long as they are stable or improving and approved by the study principal investigator (PI) ** Hematopoietic growth factor: At least 7 days must have elapsed since the last administration of filgrastim, or 14 days since administration of pegfilgrastim ** External beam radiation therapy (XRT): At least 7 days since the last dose of local palliative radiation therapy. Greater than 6 months must have elapsed since the last day of treatment if given total body irradiation, craniospinal irradiation
• Peripheral absolute neutrophil count (ANC) ≥ 750/uL
• Platelet count ≥ 75,000/uL (no platelet transfusion within 7 days prior to obtaining laboratory result)
• Creatinine clearance or glomerular filtration rate ≥ 60ml/min/1.73m^2 (calculated or measured as appropriate for age and level of concern by treating medical doctor [MD])
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age * Due to the risk of hepatic injury, including fatal hepatic failure, pazopanib should not be administered if total bilirubin is > 3.0 mg/dl or if total bilirubin is > 2.0 mg/dl and serum glutamic pyruvic transaminase (SGPT)(alanine aminotransferase [ALT]) > 3 x ULN
• SGPT (ALT) ≤ 3 x ULN * Due to the risk of hepatic injury, including fatal hepatic failure, pazopanib should not be administered if total bilirubin is > 3.0 mg/dl or if total bilirubin is > 2.0 mg/dl and SGPT(ALT) > 3 x ULN
• Serum albumin ≥ 2 gm/dL * Due to the risk of hepatic injury, including fatal hepatic failure, pazopanib should not be administered if total bilirubin is > 3.0 mg/dl or if total bilirubin is > 2.0 mg/dl and SGPT(ALT) > 3 x ULN
• Participants must be able to swallow oral tablet medication

Exclusion Criteria

• Organ dysfunction not meeting above inclusion criteria
• Pediatric subjects who are considered wards of some entity
• Patients that are organ transplant recipients or have undergone autologous or allogeneic stem cell transplant
• Pregnant or breast-feeding woman will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies
• Concomitant Medications: * Growth factor: Growth factors that support platelet or white cell number or function must not have been administered within the past 7 days * Investigational drugs: Patients who are currently receiving another investigational drug * Anti-cancer agents: Patients who are currently receiving other anti-cancer agents * Medication allergy: ** Allergy or intolerance to agents on this protocol: Trabectedin. pazopanib, ipilimumab or nivolumab * Infection: Patients who have uncontrolled infection, positive blood cultures within the past 48 hours, or receiving treatment for Clostridium difficile infection
• Known history of human immunodeficiency virus (HIV) infection
• Known active infection of hepatitis B or hepatitis C virus