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

Early Phase 1

• Conditions: Endometrial Cancer Stage I
• Interventions: Drug: PD-1 inhibitor combined progesterone; Drug: progesterone

• Registration Number: NCT04046185
• Lead Sponsor: Shanghai First Maternity and Infant Hospital

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2019-07-26
• Status Verified: 2019-08
• Study First Submitted QC: 2019-08-05
• Last Update Submitted: 2019-08-05
• Study First Posted: 2019-08-06
• Last Update Posted: 2019-08-06
• Study Start: 2019-10-01
• Primary Completion: 2021-10-01
• Study Completion: 2022-10-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 60

Inclusion Criteria

1. Early endometrial cancer patients (cancer confined in the endometrium, endometrioid histology, G1-2)
2. Patients want to preserve fertility
3. Informed consent acquired
4. Age <18, >= 45
5. Eastern Cooperative Oncology Group (ECOG) performance status score <=1
6. Normal blood routine test
7. Normal hepatic and renal function
8. Normal thyroid function
9. Patients willing to accept three times of hysteroscopy: before treatment, 3 months after treatment, 6 months after treatment.
10. Pregnancy test negative before treatment

Exclusion Criteria

1. Patients are receiving immune-checkpoint inhibitor therapy
2. Patients need or request to receive other anti-cancer drug treatment such as chemotherapy
3. Patients are allergic to immune-checkpoint inhibitor agents
4. Patients have abnormal blood routine test results or impaired hepatic and renal functions
5. Patients have a history of cardiovascular disease, including severe hypertension, frequent cardiac arrhythmia, history of myocardial infarction
6. Patients have a history of hepatitis B or hepatitis C infection, with detectable virus load
7. Severe obstructive lung disease
8. Autoimmune disease
9. Need to receive daily corticosteroid or other immune-inhibitory agents
10. Active tuberculosis patients
11. Patients have a history of other malignant tumors
12. Patients with acute infectious disease

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
pd-1 inhibitor and progesterone	PD-1 inhibitor combined progesterone	Toripalimab. 240mg intravenous injection, every 3 weeks, 4 times. Megestrol Acetate Tablets, 160mg, po, once a day.
progesterone	progesterone	Megestrol Acetate Tablets, 160mg, po, once a day.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
pregnancy rate	up to 2 years after treatment	pregnancy rate was recorded after treatment
adverse effects	up to 1 year after treatment	side effects was evaluated every 2 weeks during treatment