Overview
To find out if receiving standard chemotherapy (doxorubicin and trabectedin) can extend the cancer-free survival of patients with Stage 1b/2 uterine leiomyosarcoma who had surgery that fully removed the tumor.
Description
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
Eligibility
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 \> 2.8mg/dL
- 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.
