Programmed Death-1(PD-1) Inhibitor Combined With Progesterone Treatment in Endometrial Cancer

Study Overview
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Brief Summary
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We want to make a comparison of PD-1 inhibitor combined with progesterone versus progesterone alone in the treatment of early stage endometrial cancer patients who want to preserve fertility.

Detailed Description
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Approximately 63,400 new cases of endometrial cancer are diagnosed annually in China. While the initial treatment for early-stage disease is surgical staging with lymphadenectomy, it is apparently inappropriate for young patients who want to preserve fertility. Currently the standardize treatment for these patients are high-dose progesterone, which will be effective in approximately 40 70% patients. Mirena have been used recently as a new available treatment option, however, no concrete evidence shows it is more effective than the traditional progesterone treatment. PD-1 inhibitor has been utilized as a salvage treatment in many cancers including ovarian cancer, cervical cancer, lung cancer, gastric cancer and endometrial cancer. As endometrial cancer showed high microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) rates, it is assumed to be highly responsive to PD-1 inhibitor treatment. Published clinical trial results showed that PD-1 inhibitor treatment was effective in 6/24 late-stage endometrial cancer patients, with little or mild side effects. Here we want to investigate the efficacy of PD-1 inhibitor combined with progesterone in early stage endometrial cancer patients who want to preserve fertility.

Official Title
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PD-1 Inhibitor Combined With Progesterone Treatment in Early Stage Endometrial Cancer Patients Who Want to Preserve Fertility

Conditions
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Endometrial Cancer Stage I

Intervention / Treatment
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* Drug: PD-1 inhibitor combined progesterone
* Drug: progesterone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Early endometrial cancer patients (cancer confined in the endometrium, endometrioid histology, G1-2) Patients want to preserve fertility Informed consent acquired Age <18, >= 45 Eastern Cooperative Oncology Group (ECOG) performance status score <=1 Normal blood routine test Normal hepatic and renal function Normal thyroid function Patients willing to accept three times of hysteroscopy: before treatment, 3 months after treatment, 6 months after treatment. Pregnancy test negative before treatment Exclusion Criteria: Patients are receiving immune-checkpoint inhibitor therapy Patients need or request to receive other anti-cancer drug treatment such as chemotherapy Patients are allergic to immune-checkpoint inhibitor agents Patients have abnormal blood routine test results or impaired hepatic and renal functions Patients have a history of cardiovascular disease, including severe hypertension, frequent cardiac arrhythmia, history of myocardial infarction Patients have a history of hepatitis B or hepatitis C infection, with detectable virus load Severe obstructive lung disease Autoimmune disease Need to receive daily corticosteroid or other immune-inhibitory agents Active tuberculosis patients Patients have a history of other malignant tumors Patients with acute infectious disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pd-1 inhibitor and progesterone<br>Toripalimab. 240mg intravenous injection, every 3 weeks, 4 times. Megestrol Acetate Tablets, 160mg, po, once a day. | Drug: PD-1 inhibitor combined progesterone<br>* Toripalimab combine with progesterone<br>* Other names: Toripalimab combine with progesterone;|
| Active Comparator: progesterone<br>Megestrol Acetate Tablets, 160mg, po, once a day. | Drug: progesterone<br>* progesterone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic complete remission rate of endometrial curettage tissues | Hysteroscopy was performed 6 months after treatment. If the pathological results are normal, it is considered to be complete remission | 6 months | 
| Pathologic partial remission rate of endometrial curettage tissues | Hysteroscopy was performed 6 months after treatment. If the pathological results showed hyperplasia, it is considered to be partial remission | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse effects | side effects was evaluated every 2 weeks during treatment | up to 1 year after treatment | 
| pregnancy rate | pregnancy rate was recorded after treatment | up to 2 years after treatment |