Phase III Randomized Double-Blind Placebo-Controlled Trial of Letrozole Maintenance Therapy in Epithelial Ovarian Cancer Post-Surgery and Chemotherapy

The primary objective of this study is to evaluate the efficacy of **letrozole** maintenance therapy in patients with **epithelial ovarian cancer** following standard surgical and chemotherapy treatment. The efficacy will be measured by comparing **Progression Free Survival (PFS)** between patients receiving letrozole and those receiving a placebo. This objective is clinically relevant as it aims to determine whether letrozole can extend the period during which the disease does not worsen, potentially offering a significant improvement in patient outcomes.

The clinical trial involves a total of **240 participants** diagnosed with **epithelial ovarian cancer**. The study population is exclusively female, with an age range of 18 years and older. Participants were selected based on specific criteria, including a confirmed diagnosis of primary, newly diagnosed FIGO Stage II to IV serous or endometrioid epithelial ovarian, fallopian tube, or peritoneal cancer. All participants have undergone (interval-) debulking surgery and have completed at least four cycles of platinum-based chemotherapy. The trial excludes male subjects and does not involve a vulnerable population. Participants are required to have an ECOG-Performance Status of 0-2 and must have available paraffin-embedded tissue or cell blocks for analysis. Additionally, they must demonstrate positivity for ER expression as determined by the Histopathology Core Facility of the MATAO trial. The trial does not specify any particular lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the efficacy of **letrozole** as a maintenance therapy in patients with epithelial ovarian cancer. This is a randomized, double-blind, placebo-controlled, multi-center Phase III trial. The primary objective is to assess the **progression-free survival** (PFS) of patients receiving letrozole compared to those receiving a placebo. The trial is expected to run until June 2037, with recruitment having commenced in October 2022.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, ECOG performance status, and prior treatment history. Following randomization, participants will attend regular follow-up visits to monitor their health status, adherence to the treatment regimen, and any adverse events. The end-of-study visit will conclude the participant's involvement, during which final assessments will be conducted to evaluate the outcomes of the intervention.

The expected duration of participant involvement is up to 60 months, corresponding to the maximum treatment period with letrozole or placebo. Conditions that may lead to early termination from the study include disease progression, unacceptable toxicity, withdrawal of consent, or any other medical condition that, in the investigator's opinion, warrants discontinuation of the study treatment.

Key elements of the research methodology include the use of a placebo control to ensure blinding, and the stratification of participants based on factors such as FIGO stage and histological subtype. The primary endpoint is PFS, while secondary endpoints include overall survival, quality-adjusted progression-free survival, time until first subsequent therapy, and quality-adjusted time without symptoms and toxicity. These endpoints will provide comprehensive insights into the therapeutic benefits and safety profile of letrozole in this patient population.

The clinical trial involves the administration of **LETROZOLE**, a chemical substance classified under the ATC code L02BG04. LETROZOLE is provided in a pharmaceutical form identified as PHF00082MIG. The medication is administered orally at a dosage of 2.5 mg per day. The maximum treatment period for LETROZOLE is 60 days. This experimental medication is used as a maintenance therapy following standard surgical and chemotherapy treatment in patients with epithelial ovarian cancer. The primary objective is to evaluate its efficacy in prolonging Progression Free Survival (PFS) compared to no maintenance therapy.

The trial also includes a **placebo** group, which receives a matching placebo to the FEM345 2.5 mg film-coated tablets. The placebo consists of a mixture of inactive excipients, compressed and coated to resemble the active drug product. The placebo is administered orally, following the same dosing schedule as the experimental medication, with a maximum treatment period of 60 days. The use of a placebo allows for a double-blinded study design, ensuring that neither the participants nor the investigators are aware of the treatment assignments, thereby reducing bias in the assessment of the treatment's efficacy.

The efficacy of letrozole maintenance therapy in the treatment of epithelial ovarian cancer will be assessed primarily through **Progression-Free Survival (PFS)**. PFS is defined as the time from randomization until the date of progression (recurrence) or death by any cause in the absence of progression. This primary endpoint will provide a direct measure of the treatment's effectiveness in delaying disease progression compared to placebo.

Secondary endpoints include **Overall Survival (OS)**, which measures the time from randomization until death from any cause, and **Quality-Adjusted Progression Free Survival (QAPFS)**, which considers the quality of life during the progression-free period. Additionally, **Time until First Subsequent Therapy (TFST)** will be evaluated, defined as the time from randomization until the initiation of the next anticancer treatment. **Quality adjusted Time Without appearance of any Symptoms and Toxicity (Q-TWiST)** will also be assessed, focusing on the time from randomization until death, considering both cancer progression and medication side effects.