Endometrial Cancer
Conditions
Keywords
Early-stage endometrial cancer, Fertility-sparing, Progestin resistance, Cadonilimab, Combination immunotherapy
Brief summary
This is a single-center, prospective, open-label, single-arm exploratory phase II study evaluating the efficacy and safety of cadonilimab combined with megestrol acetate as fertility-sparing treatment for patients with progestin-resistant early-stage endometrial cancer. Approximately 10 participants will be enrolled. Participants will receive cadonilimab 6 mg/kg intravenously every 3 weeks in combination with oral megestrol acetate 160 mg once daily. The primary outcomes are complete response rate (CRR) and duration of complete response (DOR). The study will also assess treatment-related adverse events, recurrence, pregnancy, and live birth outcomes.
Detailed description
This study is a single-center, prospective, open-label, single-arm, exploratory Phase II clinical trial designed to evaluate the efficacy and safety of cadonilimab combined with megestrol acetate for fertility-sparing treatment in patients with progestin-resistant early-stage endometrial cancer. The study plans to enroll approximately 10 patients with Grade 1 endometrioid endometrial carcinoma, no myometrial invasion, no distant metastasis, and a strong desire to preserve fertility. Participants will receive cadonilimab 6 mg/kg intravenously every 3 weeks in combination with oral megestrol acetate 160 mg once daily. Treatment response will be assessed approximately every 12 weeks, with a maximum efficacy observation period of 6 months. Participants who achieve two consecutive pathological complete responses will discontinue both treatments and enter maintenance management with a levonorgestrel-releasing intrauterine system. Participants who do not achieve complete response within 6 months, experience disease progression, or develop intolerable adverse events will discontinue the study treatment and be evaluated for standard or other appropriate treatment.
Interventions
DRUGCadonilimab
Cadonilimab 6 mg/kg will be administered by intravenous infusion every 3 weeks in combination with oral megestrol acetate. Treatment response will be assessed approximately every 12 weeks, with a maximum efficacy observation period of 6 months.
Megestrol acetate 160 mg will be administered orally once daily in combination with cadonilimab. Treatment response will be assessed approximately every 12 weeks, with a maximum efficacy observation period of 6 months.
COMBINATION_PRODUCTLevonorgestrel-releasing intrauterine system
Participants who achieve two consecutive pathological complete responses will discontinue cadonilimab and megestrol acetate and receive a levonorgestrel-releasing intrauterine system for maintenance management and subsequent follow-up.
Sponsors
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single-group, open-label study in which all participants receive cadonilimab combined with megestrol acetate.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Aged 18-45 years. * Endometrioid adenocarcinoma. * Grade 1 (G1). * MRI rules out myometrial invasion. * MRI rules out myometrial invasion. * Progestin resistance (failure to achieve remission, partial response, or disease progression after 6 months of progestin therapy). * Strong desire to preserve fertility.
Exclusion criteria
* Currently receiving treatment with an immune checkpoint inhibitor. * Patients who require or request treatment with other anticancer agents, such as chemotherapy. * Patients who are allergic to immune checkpoint inhibitor drugs; * Patients with abnormal complete blood count results or impaired hepatic or renal function. * Patients with a history of cardiovascular disease, including severe hypertension, frequent arrhythmias, or myocardial infarction. * Patients with a history of hepatitis B or hepatitis C infection and a detectable viral load. * Patients with severe obstructive pulmonary disease. * Patients with autoimmune diseases. * Patients requiring daily treatment with corticosteroids or other immunosuppressive agents. * Patients with active pulmonary tuberculosis. * Patients with a history of other malignancies. * Patients with a history of other malignancies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Complete Response (DOR) | From the date of first documented CR until disease recurrence, progression, or the last follow-up, up to 36 months. | The time from the date of first documented pathological complete response (CR) to disease recurrence, disease progression, or the last follow-up. |
| Complete Response Rate (CRR) | Up to 6 months after treatment initiation | The proportion of participants who achieve pathological complete response (CR), defined as no evidence of endometrial cancer or atypical hyperplasia on histopathological examination of endometrial tissue obtained by hysteroscopy-guided endometrial biopsy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence Rate | From the date of first documented complete response until recurrence or the last follow-up, up to 36 months. | The proportion of participants who achieve complete response and subsequently develop histologically confirmed recurrence of endometrial cancer or atypical hyperplasia, or new pelvic or extra-pelvic lesions on imaging. |
| Incidence of Adverse Events | From treatment initiation through the end of the treatment period, up to 6 months. | The incidence, type, and severity of adverse events, serious adverse events, immune-related adverse events, and progestin-related adverse reactions will be assessed and graded according to CTCAE. |
| Pregnancy Rate | From treatment completion through follow-up, up to 24 months. | The proportion of participants attempting conception who achieve a pregnancy lasting more than 12 weeks after treatment. |
| Live Birth Rate | From treatment completion through follow-up, up to 36 months. | The proportion of participants who achieve pregnancy and subsequently deliver a live-born infant. |
| Changes in Serum Tumor Markers | Baseline and during treatment, up to 6 months. | Changes in serum tumor marker levels, such as CA125, from baseline to post-treatment assessment will be evaluated. |
Outcome results
None listed