Refining Fertility-sparing Treatment in Endometrial Carcinoma Based on Molecular Classification

Sponsor
Fudan University
Study ID
NCT07319429
Phase
PHASE2/PHASE3
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
FEMALE
Age
18 Years - 45 Years
Healthy Volunteers
Not accepted

Interventions

  • PD1 antibody — DRUG
    Administration: 200 mg via intravenous infusion, once every 3 weeks. After no lesions are detected in two consecutive pathological examinations, the patient enters the maintenance treatment phase. The maintenance treatment duration shall not exceed 6 months. During the maintenance period, 400 mg via intravenous infusion is administered once every 6 weeks, for 4 consecutive times.
  • Medroxyprogesterone Acetate 500 MG — DRUG
    \- Medroxyprogesterone Acetate: 500 mg, orally once daily, continuously.
  • Megestrol Acetate 160 MG — DRUG
    \- Megestrol Acetate: 160 mg, orally once daily, continuously.
  • GnRH agonist and Letrozole — DRUG
    * Triptorelin Acetate for Injection (or similar drugs): 3.75 mg per vial, intramuscular injection once every 4 weeks as one treatment course. * Letrozole Tablets: 2.5 mg, orally once daily, continuously. In the clinical trial conducted at the same center, only the same drug from the same manufacturer shall be used as the trial medication.

Study Details

Endometrial cancer (EC) stands among the most common gynecological malignancies in developed countries and regions, with a notable trend toward younger age at onset. Correspondingly, the demand for fertility-sparing treatment (FST) has been increasingly prominent among young EC patients. High-potency progestogens remain the sole therapeutic option recommended by international guidelines for this patient population; however, approximately 30% of patients exhibit no response to such treatment. The concept of EC molecular subtyping, proposed by The Cancer Genome Atlas (TCGA) in 2013, has revolutionized the diagnosis and management of EC. EC subtypes with distinct molecular features demonstrate substantial differences in biological behaviors and responses to pharmacotherapeutic interventions. Nevertheless, the role of molecular subtyping in guiding FST decision-making-both in terms of its applicability and specific mechanisms-remains an unmet research need worldwide. Notably, the POLE-mutant and microsatellite instability-high (MSI-H) subtypes display the highest sensitivity to immune checkpoint inhibitors, underscoring the clinical value of exploring their utility in FST. The no specific molecular profile (NSMP) subtype is sensitive to progestogens but lacks reliable predictive biomarkers-accurate pre-treatment prediction would enable tailored treatment selection, shorten treatment duration, and enhance therapeutic outcomes. In contrast, the p53-abnormal (p53abn) subtype is associated with a poor prognosis, and FST is therefore not recommended for this subgroup. Building on the aforementioned background and our research team's preliminary clinical findings, this project focuses on the field of FST for EC. To address the current challenges-including narrow indications, limited treatment options, suboptimal efficacy, and the absence of precise personalized regimens-we aim to conduct the world's first prospective multicenter umbrella trial based on EC molecular subtyping. Optimal novel diagnostic and therapeutic protocols will be developed for each molecular subtype, with the goals of optimizing existing FST strategies, improving FST efficacy and reproductive outcomes, expanding eligible indications, and providing high-quality clinical evidence for molecular subtype-guided FST in EC, thereby advancing the overall effectiveness of FST for EC patients.

Key Dates

First listed
Jan 6, 2026
Start date
Jan 25, 2026
Status verified
Mar 2026
Primary completion
Dec 31, 2027
Completion
Dec 31, 2029

Study Design

Enrollment
260 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT

Arms

  • Experimental: POLEmut Stage II Single-Arm Interventional Study
    Enroll patients with FIGO 2023 Stage IA POLE-mutant endometrial carcinoma to evaluate the CR rate, CR duration, and reproductive outcomes of ICI monotherapy in FST with expanded indications. Enrolled patients will receive ICI monotherapy.
  • Experimental: MMRd Stage II Single-Arm Interventional Study:
    Stratify patients based on MLH1 methylation status/MMR coding gene mutation status. Patients with MMR coding gene mutations (somatic/germline) will receive ICI monotherapy; MMRd patients with MLH1 promoter methylation will receive ICI combined with high-dose potent progestogens (PD-1 + MPA/MA). The study will evaluate the CR rate, CR duration, and reproductive outcomes of FST with expanded indications.
  • Experimental: NSMP Stage III Two-Arm Interventional Study
    Based on the prediction model, progestogen-sensitive patients will receive high-dose potent progestogens (MA/MPA); progestogen-insensitive patients will receive "GnRHa combined with letrozole". The study will evaluate FST efficacy and reproductive outcomes while further validating the predictive value of the model.Exclusion from FST: NSMP EC with ER negativity and/or L1CAM positivity (≥10%) or p53abn endometrial carcinoma.

Primary Outcome Measure

The complete response rate (CRR) at 32 weeks after initiating treatment. [ Time Frame: 32 full weeks following the first administration of fertility-preserving treatment for early-stage endometrial cancer patients. ]

Central Contacts

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