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

Primary Objective:

To evaluate disease-free survival (DFS) in patients with AJCC stage 1b, 2 and 3 uterine leiomyosarcoma receivingadjuvant chemotherapy by standard-of-care doxorubicin and trabectedin for 6 cycles

Secondary Objectives:

* To assess overall survival (OS) in patients with AJCC stage 1b, 2 and 3 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 AJCC stage 1b, 2 and 3 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 AJCC stage 1b, 2 and 3 uterine leiomyosarcoma receiving adjuvant chemotherapy by standard-of-care doxorubicin and trabectedin for 6 cycles

Exploratory Objectives

* To analyze ctDNA dynamics as a predictor of treatment response and recurrence risk, in patients with AJCC stage 1b, 2 and 3 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
* To assess the feasibility of delivering protocol-specified adjuvant chemotherapy (doxorubicin-trabectedin) using a decentralized clinical trial model.
* To assess patient satisfaction and acceptability of decentralized trial participation based on Study Participant Feedback Questionnaire (SPFQ).
* To compare protocol adherence, data completeness, and safety monitoring fidelity between centralized and decentralized participants.
* To explore the impact of decentralization on patient access, representativeness, and trial retention.

• Trabectedin (Drug): Given by IV Infusion
• Doxorubicin Hydrochloride (Drug): Given by IV Infusion

Primary outcomes

• Safety and Adverse Events (AEs) [Through study completion; an average of 1 year]: Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

Sex: Female, ages: 18 Years to any

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 30 days.
* 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.

• Elise Nassif Haddad, MD, Principal investigator, M.D. Anderson Cancer Center