Cabozantinib and Temozolomide for the Treatment of Unresectable or Metastatic Leiomyosarcoma or Other Soft Tissue Sarcoma

Inclusion Criteria: * Subjects must have a histologically confirmed diagnosis of unresectable or metastatic: * Uterine and non-uterine leiomyosarcoma * Other soft tissue sarcoma (non-leiomyosarcoma) * Note: Subjects with any one of the following soft tissue sarcoma histological subtypes will not be eligible for participation: alveolar soft-part sarcoma, dermatofibrosarcoma, gastrointestinal stromal tumor (GIST), Kaposi sarcoma, mixed mesodermal tumor/carcinosarcoma, rhabdomyosarcoma (embryonal and alveolar), and low grade (grade 1) sarcomas * Subjects must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 * Subjects with 0 - 5 prior chemotherapy regimens for recurrent/metastatic disease are eligible. It will be up to the investigator to determine what constitutes a regimen in each case * Subjects with prior next generation sequencing (NGS) reports completed on their tumor specimen will have this data collected * Subjects must have measurable disease by RECIST 1.1 * Subjects must have adequate organ and bone marrow function, based upon meeting all of the following laboratory: * White blood cell count \>= 2500/mm\^3 (\>= 2.5 GI/L) * Absolute neutrophil count (ANC) \>= 1,500/mm\^3 (\>= 1.5 GI/L) without granulocyte colony stimulating factor support * Hemoglobin \>= 9 g/dL (\>= 90 g/L) * Platelets \>= 100,000/mm\^3 (\>= 100 GI/L) without transfusion * Total bilirubin =\< 1.5 x upper limit of normal (ULN) (for subjects with Gilbert's disease =\…