Clinical trial NCT06102863: Progesterone Therapeutic Regimen Plus Statins in Young Women With Early Endometrial Carcinoma and Atypical Endometrial Hyperplasia
Official title: Progesterone Therapeutic Regimen Plus Statins in Young Women With Early Endometrial Carcinoma and Atypical Endometrial Hyperplasia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Atypical Endometrial Hyperplasia and Endometrial Carcinoma Stage I
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
Collaborators: name: Beihang University
name: Peking University
First posted: 2023-10-26
Enrollment: 38
Sex: FEMALE
Minimum age (years): 17
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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).
Primary purpose: TREATMENT

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.

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.

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. The administration regimen for the two groups was as follows:

1. Control group: progesterone regimen (oral medroxyprogesterone acetate tablet 250mg-500mg/ day or Mirena +GnRHa 3.75mg subcutaneous injection monthly);
2. 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.

Eligibility criteria: Inclusion Criteria:

* The pathological types are consistent with:

  1. Atypical endometrial hyperplasia;
  2. Patients with highly differentiated endometrioid adenocarcinoma, stage IA, and pelvic and abdominal MRI before treatment excluded deep muscle infiltration, cervical involvement, and extrauterine metastasis;
  3. There is a strong need to preserve reproductive function; Age ≤45 years old;
  4. Progesterone resistant patients predicted by the progesterone sensitivity prediction model (NCT05647109) established by our team in the previous study of endometrial cancer were prospectively randomized; The predicted progesterone sensitive patients were prospectively observed;
  5. Informed consent and signed informed consent;
  6. have follow-up conditions and are willing to continue to follow the visitors in the hospital;
  7. Patients with normal/abnormal blood lipids who have not taken any lipid-lowering drugs;
  8. A. 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)

Primary outcomes:
measure: Pathological cumulative complete response rate;
timeFrame: assessed up to 7 months
Secondary outcomes:
measure: Pathological cumulative complete response rate;
timeFrame: assessed up to 4 months
measure: The lipid content (lipid droplet, cholesterol and triglyceride) in endometrial lesion tissue
timeFrame: assessed up to 7 months
measure: Overall complete response rate
timeFrame: up to 2 years
measure: Relapse rate
timeFrame: up to 15 months after the end of treatment.
measure: Toxic Side Effect
timeFrame: up to 3 months after the end of treatment.
measure: Pregnancy rate
timeFrame: up to 15 months after the end of treatment.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
Study officials:
affiliation: Peking University /Peking University People&#39;s Hospital
name: Jianliu Wang, professor
role: STUDY_DIRECTOR
References: