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

Primary Objective:

To evaluate disease-free survival (DFS) in patients with FIGO stage 1b and 2 uterine leiomyosarcoma receiving adjuvant chemotherapy by standard-of-care doxorubicin and trabectedin for 6 cycles

Secondary Objectives:

To assess overall survival (OS) in patients with FIGO stage 1b and 2 uterine leiomyosarcoma receiving adjuvant chemotherapy by standard-of-care doxorubicin and trabectedin for 6 cycles

• To characterize treatment-related toxicity according to Common Terminology Criteria for Adverse Events (CTCAE), in patients with FIGO stage 1b and 2 uterine leiomyosarcoma receiving adjuvant chemotherapy by standard-of-care doxorubicin and trabectedin for 6 cycles
• To evaluate quality of life (QoL) outcomes using patient-reported measures in patients with FIGO stage 1b and 2 uterine leiomyosarcoma receiving adjuvant chemotherapy by standard-of-care doxorubicin and trabectedin for 6 cycles
• To analyze ctDNA dynamics as a predictor of treatment response and recurrence risk, in patients with FIGO stage 1b and 2 uterine leiomyosarcoma receiving adjuvant chemotherapy by standard-of-care doxorubicin and trabectedin for 6 cycles
• To estimate the incidence of germline genetic alterations in patients with localized 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.