Using Letrozole to Prevent Recurrence in Endometrial Cancer Patients

Letrozole as Maintenance Therapy Versus Observation After Adjuvant Treatment on the Prognosis for Post-surgical Endometrial Cancer Patients With Non-specific Molecular Profile: a Superiority Randomized Controlled Trial

This study is testing if the drug Letrozole can help prevent endometrial cancer from coming back in patients who have had surgery and are at risk for recurrence.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 299 (estimated)
• Ages: 18 Years to 80 Years
• Sex: Female
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: immunotherapy, chemotherapy
• Locations: 1 site (Shanghai)
• Trial ID: NCT05454358 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of Letrozole as a maintenance therapy for post-operative patients with endometrial cancer who have a non-specific molecular profile (NSMP). It is an open-label, multi-center, randomized controlled trial designed to assess whether Letrozole can reduce recurrence rates and improve survival outcomes after initial adjuvant treatment. The study focuses on patients who have undergone surgery, including hysterectomy and other procedures, and aims to provide a potential new treatment option for those at intermediate to high risk of recurrence. By targeting the hormonal sensitivity of NSMP endometrial cancers, the trial seeks to enhance patient prognosis with minimal side effects.

Who should consider this trial

Good fit: Ideal candidates for this study are adults over 18 years old who have been diagnosed with stage I-IV endometrial epithelial cancer and have undergone the necessary surgical procedures.

Not a fit: Patients with endometrial cancer types that do not fall under the non-specific molecular profile or those with a life expectancy of less than two years may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the risk of cancer recurrence and improve survival rates for patients with NSMP endometrial cancer.

How similar studies have performed: Previous studies have shown promising results with hormonal therapies in similar contexts, suggesting that this approach may be effective, although the specific use of Letrozole in this setting is novel.

Eligibility criteria

Inclusion Criteria:

1. Older than 18 years old;
2. Initial diagnosed with stage I-IV(FIGO2009) endometrial epithelial cancer, regardless of pathological types;
3. Surgery must have included a hysterectomy, bilateral salpingo-oophorectomy and sentinel node biopsy; pelvic lymph node sampling and para-aortic lymph node sampling are optional;
4. Life expectancy of 2 or more years.
5. Confirmed NSMP with intermediate or higher prognostic risk according to post-operative clinical pathological assessment and molecular classification;

   1. Intermediate prognostic risk group:

      * Stage lB endometrioid + Iow-grade\* + LVSI negative or focal
      * Stage IA endometrioid + high-grade\*+ LVSI negative or focal
      * Stage IA non-endometrioid (serous, clear cell, undifferentiated carcinoma, carcinosarcoma, mixed) without myometrial invasion
   2. High-intermediate prognostic risk group:

      * Stage I endometrioid + substantial LVSI, regardless of grade and depth of invasion
      * Stage lB endometrioid high-grade\*, regardless of LVSI status
      * Stage II
   3. High prognostic risk group:

      * Stage Ill-IVA with no residual disease
      * Stage I-IVA non-endometrioid (serous, clear cell, undifferentiated carcinoma, carcinosarcoma, mixed) with myometrial invasion, and with no residual disease
   4. Advanced Metastatic:

      * Stage III-IVA with residual disease
      * Stage IVB Low grade: G1-2; High grade:G3;
6. Received conventional adjuvant therapy after surgery according to the latest version of NCCN or ESGO/ESTRO/ESP guidelines;
7. Patients with residual tumor after surgery (any single site) must have achieved complete response or partial response after post-operative adjuvant therapy;
8. Expected start of letrozole maintenance within 3 months after adjuvant therapy;
9. Adequate organ function as defined by the following criteria:

   * White blood cell (WBC) ≥ 3000/μL or Absolute neutrophil count (ANC) ≥1500/μL
   * Platelets ≥100,000/μL
   * Serum Aspartate transaminase (AST) and/or serum alanine transaminase (ALT) ≤ 2 times upper limit of normal (ULN)
   * Serum creatinine ≤2 times ULN
10. Karnofsky score ≥60;
11. Eastern Cooperative Oncology Group (ECOG) Performance status ≤2;
12. Ability to take anti-thyroid drugs, calcium, vitamin D or bisphosphonates together.

Exclusion Criteria:

1. Endometrial stromal tumor;
2. Recurrent endometrial cancers;
3. Patients with low prognostic risk according to post-operative clinical pathological assessment ( Stage IA endometrioid + low-grade\* +LVSI negative or focal);
4. Patients require no adjuvant therapy after surgery;
5. Negative expression in estrogen receptor or progesterone receptor according to post-operative Immunohistochemistry;
6. Received other adjuvant therapy within 6 months before surgery: including neoadjuvant therapy, hormone therapy, targeted therapy, immunotherapy and biotherapy, etc;
7. Patients with contraindications for letrozole;
8. Patients with other malignant tumors;
9. History of vital organ transplantation;
10. History of immune disease and need to take immunosuppressor;
11. Uncontrolled psychiatric illness or other situations that would limit compliance with study requirements;
12. History of drug abuse;
13. Participated in other clinical trials;
14. No ability or intention to receive letrozole maintenance/sign the consent/obey the study requirements.

Where this trial is running

Shanghai

• Obstetrics and Gynecology Hospital of Fudan University — Shanghai, China (Recruiting)

Study contacts

• Principal investigator: Xiaojun Chen, Ph.D, M.D — Obstetrics & Gynecology Hospital of Fudan University
• Study coordinator: Xiaojun Chen, Ph.D, M.D

Conditions Endometrial Cancer; endometrial cancer; letrozole; maintenance therapy; molecular classification; non-specific molecular profile