Progesterone Therapeutic Regimen Plus Statins in Young Women With Early Endometrial Carcinoma and Atypical Endometrial Hyperplasia

Sponsor

Peking University People's Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT06102863

Collaborator

(none)

Enrollment

Location

Arms

22.1

Anticipated Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To explore the treatment efficacy of Progesterone Therapeutic Regimen Plus Statins in patients with atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EEC) for conservative treatment.

Condition or Disease	Intervention/Treatment	Phase
Atypical Endometrial Hyperplasia and Endometrial Carcinoma Stage I	Drug: statins (oral atorvastatin calcium tablet 20mg/ day; Or rosuvastatin 5mg/ day; Or pivastatin 2mg/ day);	Phase 2

Detailed Description

After diagnosed of AEH or EEC by hysteroscopy, patients meet the study criteria will be enrolled. The lipid content (lipid droplet, cholesterol and triglyceride) in endometrial lesion tissue was detected by Raman scattering instrument. And Age, height, weight, waistline, blood pressure, basic history of infertility and family cancer will be collected. Blood tests, including fasting blood glucose (FBG), fasting insulin (FINS), blood lipids, sex hormone levels, anti-müllerian hormone (AMH) and renal/liver function tests will be performed before treatment to evacuate their basic conditions. Each subject will receive body fat testing by Inbody 770.

Control group: progesterone regimen (oral medroxyprogesterone acetate tablet 250mg-500mg/ day or Mirena +GnRHa 3.75mg subcutaneous injection monthly);
Trial group: progesterone regimen (oral medroxyprogesterone acetate tablet 250mg-500mg/ day or Mirena +GnRHa3.75mg subcutaneous injection monthly) combined with statins (oral atorvastatin calcium tablet 20mg/ day; or rosuvastatin 5mg/ day; or pivastatin 2mg/ day);

The specific selection of progesterone regimen was based on whether the patients had oral progesterone contraindications and if BMI≥28kg/m2 was not suitable for oral progesterone, Mirena +GnRHa regimen was selected. The choice of statin drugs is based on the results of the drug sensitivity test of the patient's tumor tissue, and the most sensitive one of the three drugs is selected.

For patients remained SD after 9 months of treatment but refused hysterectomy, a multiple disciplinary discussion would be held for individual case, and alternative treatment would be given. Maintenance treatment will be recommended for patients with CR, and participants will be followed up for at least 1 year.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

38 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Patients with endometrial cancer who met the inclusion criteria were randomly divided into the control group and the experimental group in a 1:1 ratio according to the random numbers generated in advance (no preset position, no specific object).Patients with endometrial cancer who met the inclusion criteria were randomly divided into the control group and the experimental group in a 1:1 ratio according to the random numbers generated in advance (no preset position, no specific object).

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Progesterone Therapeutic Regimen Plus Statins in Young Women With Early Endometrial Carcinoma and Atypical Endometrial Hyperplasia

Actual Study Start Date :

Apr 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Feb 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: control group Progesterone regimen (oral medroxyprogesterone acetate tablet 250mg-500mg/ day or mirena +GnRHa 3.75mg subcutaneous injection monthly);
Experimental: experimental group Progesterone regimen (oral medroxyprogesterone acetate tablet 250mg-500mg/ day or Mirena +GnRHa3.75mg subcutaneous injection monthly) combined with statins (oral atorvastatin calcium tablet 20mg/ day; Or rosuvastatin 5mg/ day; Or pivastatin 2mg/ day);	Drug: statins (oral atorvastatin calcium tablet 20mg/ day; Or rosuvastatin 5mg/ day; Or pivastatin 2mg/ day); Progesterone regimen (oral medroxyprogesterone acetate tablet 250mg-500mg/ day or Mirena +GnRHa3.75mg subcutaneous injection monthly) combined with statins (oral atorvastatin calcium tablet 20mg/ day; Or rosuvastatin 5mg/ day; Or pivastatin 2mg/ day);

Arm

Intervention/Treatment

No Intervention: control group

Progesterone regimen (oral medroxyprogesterone acetate tablet 250mg-500mg/ day or mirena +GnRHa 3.75mg subcutaneous injection monthly);

Experimental: experimental group

Progesterone regimen (oral medroxyprogesterone acetate tablet 250mg-500mg/ day or Mirena +GnRHa3.75mg subcutaneous injection monthly) combined with statins (oral atorvastatin calcium tablet 20mg/ day; Or rosuvastatin 5mg/ day; Or pivastatin 2mg/ day);

Drug: statins (oral atorvastatin calcium tablet 20mg/ day; Or rosuvastatin 5mg/ day; Or pivastatin 2mg/ day);

Outcome Measures

Primary Outcome Measures

Pathological cumulative complete response rate; [assessed up to 4 months]
3 to 4 months: From date of initial therapy until the date of CR or date of hysterectomy,

Secondary Outcome Measures

Pathological cumulative complete response rate; [assessed up to 8 months]
From 6 to 8 months; From date of initial therapy until the date of CR or date of hysterectomy,
The lipid content (lipid droplet, cholesterol and triglyceride) in endometrial lesion tissue [assessed up to 4 months]
The lipid content (lipid droplet, cholesterol and triglyceride) in endometrial lesion
Overall complete response rate [up to 2 years]
Pathological response duration
Relapse rate [up to 15 months after the end of treatment]
Relapse rate
Toxic Side Effect [up to 3 months after the end of treatment]
Toxicity evaluation according to CTCAE 5.0 version.

Eligibility Criteria

Criteria

Ages Eligible for Study:

17 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

The pathological types are consistent with:

Atypical endometrial hyperplasia;
Patients with highly differentiated endometrioid adenocarcinoma, stage IA, and pelvic and abdominal MRI before treatment excluded deep muscle infiltration, cervical involvement, and extrauterine metastasis;
There is a strong need to preserve reproductive function; Age ≤45 years old;
The content of cholesterol esters in endometrial cancer tissues was detected by Raman scattering technique to exceed 35%;
Informed consent and signed informed consent;
have follow-up conditions and are willing to continue to follow the visitors in the hospital;
Patients with normal/abnormal blood lipids who have not taken any lipid-lowering drugs;
1. Newly treated patients: did not use any nursery therapy drugs (progesterone, GNRH-a); B. 1 course of treatment (12 weeks) the lesions persisted; C. Partial remission for 2 courses of treatment (24 weeks);

Exclusion Criteria:

(1) Patients with severe internal diseases and severe impairment of liver and kidney function;

(2) Disease progression, extrauterine metastasis (cervical invasion or distant metastasis such as pelvic cavity) during treatment;

(3) People with therapeutic drug allergies and contraindications;

(4) Patients with other types of endometrial cancer or other malignant tumors of the reproductive system; Patients with breast cancer or other hormone-dependent tumors that cannot use progesterone;

(5) Patients with deep vein thrombosis, stroke and myocardial infarction during treatment;

(6) Alcoholics (> 20g/ day);

(7) Smokers (> 15 cigarettes/day)