Phase II Decentralized Pragmatic Trial of Adjuvant Doxorubicin - Trabectedin Chemotherapy in uLMS

Inclusion Criteria:

* Patients must have histologically confirmed uterine leiomyosarcoma
* Patients must have localized tumors, AJCC stages 1b to 3 according to the AJCC uterine sarcoma staging system (high risk of relapse population)
* Patients must have had complete surgical resection of tumor within 3 months prior to initiation of adjuvant chemotherapy, complete surgical resection includes at least a total hysterectomy
* Patients must have no evidence of residual disease, as proven by CT Chest-Abdomen-Pelvic within 28 days before randomization (exclude potential metastatic patients)
* Patients must have no history of pelvic radiation (hematologic tolerance of chemotherapy is impaired by pelvic radiation)
* No prior chemotherapy for the treatment of the uterine leiomyosarcoma
* Age ≥18 years. Because no dosing or adverse event data are currently available on the use of doxorubicin in combination with trabectedin in patients \<18 years of age, children are excluded from this study.
* ECOG performance status ≤2 (Karnofsky ≥60%,).
* Patients must have adequate organ and marrow function as defined below:
* absolute neutrophil count ≥1,000/mcL
* platelets ≥100,000/mcL
* total bilirubin ≤ institutional upper limit of normal (ULN) (except patients with Gilbert's syndrome, who must have total bilirubin \< 3.0 mg/dL)
* AST(SGOT)/ALT(SGPT) ≤2× institutional ULN
* eGFR (using 2021 CKD-EPI) ≥40mL/min/1.73m2
* Albumin \> 28 g/L
* CPK ≤2× institutional ULN
* No cardiac dysfunction as proven by LVEF\>50%
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* Patients with a prior or concurrent malignancy whose natural history or treatment does not interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

* Patients who are receiving any other investigational agents.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to doxorubicin or trabectedin or other agents used in study.
* Patients with uncontrolled intercurrent illness per clinical judgment of the study PI and/or treating physician
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* Patients with psychiatric illness/social situations that would limit compliance with study requirements.