Phase II Multicenter Study on Anastrozole, Letrozole, and Exemestane Interruption vs. Maintenance in Metastatic Low-Grade Endometrial Stromal Sarcoma

The primary objective of this study is to compare the **progression-free survival** (PFS) between strategies of interruption versus maintenance of aromatase inhibitors in patients with locally advanced or metastatic low-grade endometrial stromal sarcoma (LGESS). This comparison is clinically relevant as it aims to determine the optimal management strategy for prolonging the time patients remain free from disease progression, which is crucial for improving patient outcomes in this population.

Secondary objectives include:

• Comparing the overall survival (OS) between treatment arms.
• Evaluating the safety of the treatment strategies.
• Assessing the Quality of Life (QoL) of patients under different treatment regimens.
• Determining the time to first subsequent chemotherapy or treatment.
• Evaluating the progression-free survival after reintroduction of aromatase inhibitors in the experimental arm.
• Determining the objective response rate (ORR) after reintroduction of aromatase inhibitors in the experimental arm.
• Assessing the duration of response to aromatase inhibitors after reintroduction in the experimental arm.
• Exploratory objectives include identifying predictive factors of prolonged response to hormone therapy or late resistance using Next Generation Sequencing and Comparative Genome Hybridization.

The clinical trial involves **female** participants aged 18 years and older, diagnosed with locally advanced or metastatic low-grade **endometrial stromal sarcoma**. The study population is exclusively female, with no male participants included, and does not involve any vulnerable populations. Participants were selected based on specific criteria, including a histological confirmation of low-grade endometrial stromal sarcoma and a history of treatment with aromatase inhibitors such as Anastrozole, Exemestane, or Letrozole. The trial requires that the disease be controlled at the time of randomization, with an Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or less. Participants must also be covered by medical insurance and have provided signed informed consent. The sponsor has not provided information regarding the total number of participants in the study. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is a **randomized**, **controlled**, and **prospective** study designed to evaluate the clinical impact of interruption versus maintenance of **aromatase inhibitors** in patients with locally advanced or metastatic low-grade endometrial stromal sarcoma. The trial is conducted in a **double-blind** manner to ensure unbiased results. The primary objective is to compare the progression-free survival (PFS) between the two strategies. The trial is expected to run from January 23, 2019, to January 24, 2028, with an estimated duration of 96 months for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, histological confirmation of low-grade endometrial stromal sarcoma, and prior treatment with an aromatase inhibitor. Following randomization, participants will be assigned to either the interruption or maintenance group. Regular follow-up visits will be scheduled to monitor disease progression, overall survival, safety, quality of life, and time to first subsequent chemotherapy. The end-of-study visit will occur at the conclusion of the participant's involvement in the trial or upon reaching the study's primary endpoint.

The expected length of participant involvement is up to 96 months, contingent upon disease control and adherence to the study protocol. Conditions that may lead to early termination from the study include significant disease progression, unacceptable toxicity, withdrawal of consent, or any other medical condition that, in the investigator's opinion, warrants discontinuation. The trial will adhere to ethical standards, and participants will be required to provide informed consent prior to any study-specific procedures.

The clinical trial involves the administration of **ARIMIDEX** 1 mg, a **film-coated tablet** containing the active substance **anastrozole**. This medication is administered orally at a dosage of 1 mg per day. The maximum treatment period is 96 weeks, with a total maximum dose of 2920 mg. The medication is classified as an antineoplastic agent and is produced by Laboratoires Juvisé Pharmaceuticals. Compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment protocol.

Another experimental medication used in the trial is **LETROZOLE**, which is also administered orally. The maximum daily dose for letrozole is 2.5 mg, with a total maximum dose of 7300 mg over the 96-week treatment period. Letrozole is a chemical substance classified under the antineoplastic category. The pharmaceutical form is denoted as PHF00082MIG, and it is included in the study to evaluate its efficacy in comparison to other treatments.

The trial also includes the administration of **AROMASINE** 25 mg, a **coated tablet** containing the active substance **exemestane**. This medication is administered orally at a dosage of 25 mg per day, with a maximum total dose of 73000 mg over the 96-week treatment period. AROMASINE is produced by Pfizer Holding France and is classified as an antineoplastic agent. Participant compliance with the dosing regimen is closely monitored to ensure accurate assessment of the treatment's impact.

All medications in this trial are administered orally and are chemically derived. The study aims to compare the progression-free survival between the interruption and maintenance of aromatase inhibitors in patients with locally advanced or metastatic low-grade endometrial stromal sarcoma. No non-experimental treatments, such as standard-of-care therapy or placebo, are used in this study. The trial's design ensures rigorous monitoring of participant adherence to the prescribed dosing schedules to maintain the integrity of the study results.

Efficacy in this clinical trial will be assessed primarily through the measurement of **Progression-Free Survival (PFS)**. PFS is defined as the time from the date of randomization to the date of the first documented radiological progression, as per RECIST 1.1 criteria, or death due to any cause. This endpoint will provide a direct measure of the effectiveness of the aromatase inhibitors interruption versus maintenance strategies in patients with locally advanced or metastatic low-grade endometrial stromal sarcoma.

Secondary efficacy endpoints include overall survival (OS), safety, quality of life (QoL), and the time to first subsequent chemotherapy. Additionally, in the experimental arm, the progression-free survival after reintroduction of aromatase inhibitors, the objective response rate (ORR) after reintroduction, and the duration of response to aromatase inhibitors after reintroduction will be evaluated. These parameters will be measured and analyzed to provide a comprehensive understanding of the treatment's impact on patient outcomes.