Trabectedin, Doxorubicin and Olaratumab in Patients With Metastatic or Recurrent Leiomyosarcoma

Inclusion Criteria: 1. Histologically confirmed metastatic, advanced, or recurrent, LMS. Note: Patients should have tissue, either archival or fresh biopsy, submitted for pathologic review to confirm diagnosis of LMS. For patients with recurrent disease with disease free interval greater than six months, a fresh biopsy must be obtained. 2. All patients with recurrent or metastatic LMS deemed unresectable must have measurable disease as defined by RECIST 1.1. All patients with advanced LMS may be enrolled after an initial cytoreductive surgery if there is measurable disease as defined by RECIST 1.1. 3. Life expectancy greater than 3 months. 4. Male or female, age ≥18 years 5. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1. 6. Resolution of clinically significant toxic effects of prior surgery, radiotherapy or systemic anticancer therapy. 7. Patients must not have received prior doxorubicin chemotherapy; only 1 prior chemotherapy line allowable and must be discontinued at least 4 weeks prior to first day of study treatment. 8. Patients should be free of active infections requiring antibiotics (with exception of urinary tract infection). 9. Patients must have adequate organ and marrow function as defined below: Absolute neutrophil count (ANC) ≥1,500 cells/mm³ * Platelet count ≥100,000/mm³ * Hemoglobin ≥9.0g/dL * Total bilirubin \<1.0 upper limit of normal (ULN) * Alkaline phosphatase of non-osseous origin ≤ 2.5 x ULN * Aminotransferase (AST and ALT) ≤ 2.5 x ULN * Creatinine phosphokinase (CPK) ≤ 2.5 x ULN * Isotope Dilution Mass Spectrometry (IDMS) creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 40 mL/min * Albumin ≤ 3 g/dL\* * \*Hypoalbuminemia \< 3 g/dL should be considered carefully but in and of itself, not exclusionary. 10. Women of child-bearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation until 3 months for women and 5 months for men after completion of study drug administration. WOCBP must have a negative serum or urine test at time of enrollment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study therapy, and 5 months after completion of study drug administration. 11. Patients must have adequate cardiac function (ejection fraction ≥ 45%) to receive therapy. 12. Ability to understand the investigational nature, potential risks and benefits of the research study and to provide valid written informed consent. Exclusion Criteria: 1. Patients without histologically confirmed LMS 2. Patients without measurable disease by RECIST 1.1 criteria 3. Prior doxorubicin, trabectedin, or olaratumab chemotherapy 4. Patients with an ECOG of 2, 3 or 4 (Appendix C) 5. Patient with known allergies to pegfilgrastim/filgrastim. 6. Patients with known active central nervous system (CNS) metastasis and/or carcinomatous meningitis. 7. Use of other investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of study therapy and during the study. 8. Patients with a known sensitivity to humanized antibodies or sensitivity attributed to compounds of similar chemical or biological composition to alkylating agents or anthracyclines. 9. A QT interval corrected for heart rate using the Bazett's formula (QTcB) ≥ 480 msec. 10. Patients on combination antiretroviral therapy are ineligible. 11. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infections (including viral hepatitis), decompensated cirrhosis or chronic liver disease, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with the study requirements. 12. Adults unable to consent, pregnant or nursing women or prisoners. 13. Any serious medical or psychiatric illness/condition likely in the judgment of the Investigator(s) to interfere or limit compliance with study requirements/treatment. 14. Diagnosis of another primary malignancy within the past 5 years with the exception of non-melanoma skin cancer. 15. Patients with a prior history of grade 3 capillary leak syndrome (CLS) or \<grade 3 CLS with pulmonary involvement. 16. Unwilling to abstain from alcohol ingestion for duration of the study 17. Patients with elevated liver function or bilirubin not meeting criteria for treatment