Value of LNG-IUS as Fertility-preserving Treatment of EAH and EC
Phase 2
Recruiting
- Conditions
- Endometrial CancerAtypical Endometrial Hyperplasia
- Interventions
- Registration Number
- NCT03463252
- Lead Sponsor
- West China Second University Hospital
- Brief Summary
Primary end points:
This clinical trial is aimed to analyze the effectiveness of Levonorgestrel-Releasing Intrauterine System (LNG-IUS, Mirena®) in the fertility-sparing treatment of atypical endometrial hyperplasia and early endometrial carcinoma, including pathology response and pregnancy outcome.
Second end points:
To analyze the appearances of side-effects.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 224
Inclusion Criteria
- ≤40 years of age:
- Having a strong desire for fertility preservation;
- Histological diagnosis is confirmed as well-differentiated (grade 1) endometrioid adenocarcinoma by the designated gynecological pathologists, and the progesterone receptors (PgRs) is positive in immunohistochemistry;
- Disease limited to the endometrium (stage 1A) on MRI;
- Serum CA125/199 level is within normal limit (Laparoscopic exploration to rule out ovarian tumor or another metastasis if necessary);
- Patients should have undergone counseling to learn fertility-preserving treatment is not standard of care for the treatment of EC, volunteered to participate in this study, signed the informed consent form, and agreed to participated in clinical follow-up.
Exclusion Criteria
- Patients have allergies or contraindications (except for thromboembolic disease, liver dysfunction, hypertension, and diabetes) for the involved drugs;
- Patients have lynch syndrome (LS);
- Patients have contraindications for pregnancy;
- Patients have serious underlying disease, malignancies at other site(s), acute liver or kidney disease, acute liver or kidney diseases, acute or subacute genital tract infections and congenital or acquired abnormal uterine development (that may make intrauterine device placement impossible);
- Patients refuse to participate in clinical follow-up or sign the informed consent form.
For Patients With Endometrial atypical hyperplasia：
Inclusion Criteria:
- ≤ 40 years of age
- Having a strong desire for fertility preservation
- Histological diagnosis is confirmed as atypical endometrial hyperplasia (EAH) by the designated gynecological pathologists
- Having volunteered to participate in this study, signed the informed consent form, and agreed to participate in clinical follow-up
Exclusion Criteria:
- Patients have allergies or contraindications (except for thromboembolic disease, liver dysfunction, hypertension, and diabetes) for the involved drugs
- Patients have contraindications for pregnancy
- Patients have serious underlying disease, malignancies at other site(s), acute liver or kidney disease, acute or subacute genital tract infections, and congenital or acquired abnormal uterine development (that may make intrauterine device placement impossible)
- Patients refuse to participate in clinical follow-up or sign the informed consent form.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MPA+Mirena® for EC without contraindication Mirena® The enrolled patient (endometrial cancer without contraindication of oral high dose progesterone) is allocated to one of three groups, MPA only, MPA+LNG-IUS, LNG-IUS only, by randomization. Continuous treatment for 3 months is one cycle. Hysteroscopic evaluation and biopsy will procedure every cycle. Patients with partial response or in stable condition, after 2 cycles, will receive continuous treatment for one more cycle again. Patients with complete response after 2 or 3 cycles are encouraged to pregnancy. The consideration of giving up fertility-sparing treatment is recommended: 1) if patient have documented progression on the biopsies; 2) if endometrial cancer is still present after 3 cycles. Mirena® for EC without contraindication Mirena® The enrolled patient (endometrial cancer without contraindication of oral high dose progesterone) is allocated to one of three groups, MPA only, MPA+LNG-IUS, LNG-IUS only, by randomization. Continuous treatment for 3 months is one cycle. Hysteroscopic evaluation and biopsy will procedure every cycle. Patients with partial response or in stable condition, after 2 cycles, will receive continuous treatment for one more cycle again. Patients with complete response after 2 or 3 cycles are encouraged to pregnancy. The consideration of giving up fertility-sparing treatment is recommended: 1) if patient have documented progression on the biopsies; 2) if endometrial cancer is still present after 3 cycles. GnRH agonist+Mirena® for EC with contraindication Mirena® The enrolled patient (endometrial cancer with contraindication of oral high dose progesterone) is allocated to either GnRH-a+ LNG-IUS or only LNG-IUS by randomization. Continuous treatment for 3 months is one cycle. Hysteroscopic evaluation and biopsy will procedure every cycle. Patients with partial response or in stable condition, after 2 cycles, will receive continuous treatment for one more cycle again. Patients with complete response after 2 or 3 cycles are encouraged to pregnancy. The consideration of giving up fertility-sparing treatment is recommended: 1) if patient have documented progression on the biopsies; 2) if endometrial cancer is still present after 3 cycles. Mirena® for EC with contraindication Mirena® The enrolled patient (endometrial cancer with contraindication of oral high dose progesterone) is allocated to either GnRH-a+ LNG-IUS or only LNG-IUS by randomization. Continuous treatment for 3 months is one cycle. Hysteroscopic evaluation and biopsy will procedure every cycle. Patients with partial response or in stable condition, after 2 cycles, will receive continuous treatment for one more cycle again. Patients with complete response after 2 or 3 cycles are encouraged to pregnancy. The consideration of giving up fertility-sparing treatment is recommended: 1) if patient have documented progression on the biopsies; 2) if endometrial cancer is still present after 3 cycles. Mirena® for EAH without progesterone contraindication Mirena® The enrolled patient (atypical endometrial hyperplasia without contraindication of oral high dose progesterone) is allocated to either MPA or LNG-IUS by randomization. Continuous treatment for 3 months is one cycle. Hysteroscopic evaluation and biopsy will procedure every cycle. Patients with partial response or in stable condition, after 2 cycles, will receive continuous treatment for one more cycle again. Patients with complete response after 2 or 3 cycles are encouraged to pregnancy. The consideration of giving up fertility-sparing treatment is recommended: 1) if patient have documented progression on the biopsies; 2) if EAH is still present after 3 cycles. Mirena® for EAH with progesterone contraindication Mirena® The enrolled patient (atypical endometrial hyperplasia with contraindication of oral high dose progesterone) is allocated to either GnRH-a+ LNG-IUS or only LNG-IUS by randomization. Continuous treatment for 3 months is one cycle. Hysteroscopic evaluation and biopsy will procedure every cycle. Patients with partial response or in stable condition, after 2 cycles, will receive continuous treatment for one more cycle again. Patients with complete response after 2 or 3 cycles are encouraged to pregnancy. The consideration of giving up fertility-sparing treatment is recommended: 1) if patient have documented progression on the biopsies; 2) if EAH is still present after 3 cycles. GnRH-a+Mirena® for EAH with progesterone contraindication Mirena® The enrolled patient (atypical endometrial hyperplasia with contraindication of oral high dose progesterone) is allocated to either GnRH-a+ LNG-IUS or only LNG-IUS by randomization. Continuous treatment for 3 months is one cycle. Hysteroscopic evaluation and biopsy will procedure every cycle. Patients with partial response or in stable condition, after 2 cycles, will receive continuous treatment for one more cycle again. Patients with complete response after 2 or 3 cycles are encouraged to pregnancy. The consideration of giving up fertility-sparing treatment is recommended: 1) if patient have documented progression on the biopsies; 2) if EAH is still present after 3 cycles. GnRH-a+Mirena® for EAH with progesterone contraindication GnRH agonist The enrolled patient (atypical endometrial hyperplasia with contraindication of oral high dose progesterone) is allocated to either GnRH-a+ LNG-IUS or only LNG-IUS by randomization. Continuous treatment for 3 months is one cycle. Hysteroscopic evaluation and biopsy will procedure every cycle. Patients with partial response or in stable condition, after 2 cycles, will receive continuous treatment for one more cycle again. Patients with complete response after 2 or 3 cycles are encouraged to pregnancy. The consideration of giving up fertility-sparing treatment is recommended: 1) if patient have documented progression on the biopsies; 2) if EAH is still present after 3 cycles. GnRH agonist+Mirena® for EC with contraindication GnRH agonist The enrolled patient (endometrial cancer with contraindication of oral high dose progesterone) is allocated to either GnRH-a+ LNG-IUS or only LNG-IUS by randomization. Continuous treatment for 3 months is one cycle. Hysteroscopic evaluation and biopsy will procedure every cycle. Patients with partial response or in stable condition, after 2 cycles, will receive continuous treatment for one more cycle again. Patients with complete response after 2 or 3 cycles are encouraged to pregnancy. The consideration of giving up fertility-sparing treatment is recommended: 1) if patient have documented progression on the biopsies; 2) if endometrial cancer is still present after 3 cycles. MPA for EC without progesterone contraindication Progesterone The enrolled patient (endometrial cancer without contraindication of oral high dose progesterone) is allocated to one of three groups, MPA only, MPA+LNG-IUS, LNG-IUS only, by randomization. Continuous treatment for 3 months is one cycle. Hysteroscopic evaluation and biopsy will procedure every cycle. Patients with partial response or in stable condition, after 2 cycles, will receive continuous treatment for one more cycle again. Patients with complete response after 2 or 3 cycles are encouraged to pregnancy. The consideration of giving up fertility-sparing treatment is recommended: 1) if patient have documented progression on the biopsies; 2) if endometrial cancer is still present after 3 cycles. MPA+Mirena® for EC without contraindication Progesterone The enrolled patient (endometrial cancer without contraindication of oral high dose progesterone) is allocated to one of three groups, MPA only, MPA+LNG-IUS, LNG-IUS only, by randomization. Continuous treatment for 3 months is one cycle. Hysteroscopic evaluation and biopsy will procedure every cycle. Patients with partial response or in stable condition, after 2 cycles, will receive continuous treatment for one more cycle again. Patients with complete response after 2 or 3 cycles are encouraged to pregnancy. The consideration of giving up fertility-sparing treatment is recommended: 1) if patient have documented progression on the biopsies; 2) if endometrial cancer is still present after 3 cycles. MPA for EAH without progesterone contraindication Progesterone The enrolled patient (atypical endometrial hyperplasia without contraindication of oral high dose progesterone) is allocated to either MPA or LNG-IUS by randomization. Continuous treatment for 3 months is one cycle. Hysteroscopic evaluation and biopsy will procedure every cycle. Patients with partial response or in stable condition, after 2 cycles, will receive continuous treatment for one more cycle again. Patients with complete response after 2 or 3 cycles are encouraged to pregnancy. The consideration of giving up fertility-sparing treatment is recommended: 1) if patient have documented progression on the biopsies; 2) if EAH is still present after 3 cycles.
- Primary Outcome Measures
Name Time Method Pathologic Response 6-12 months Pathologic response to medicine treatment is categorized as complete response (CR), partial response (PR), no change (NC), and progressive disease (PD). CR is defined as the absence of any hyperplastic or cancerous lesion. PR is defined as the residual lesion with degeneration and atrophy of endometrial glands. NC is defined as residual lesion without degeneration or atrophy of endometrial glands. PD is defined as the appearance of endometrial cancer for EAH and grade 2 (G2) or 3 for EC.
Pregnancy Rate 7-144 months The percentage of successful pregnancies in the CR patients.
Live Birth Rate 16-144 months The percentage of successfully alive baby delivery in the pregnant patients.
- Secondary Outcome Measures
Name Time Method Side-Affects Rate 1-144 months The appearances of side-effects include weight gain, irregular vaginal bleeding, breast pain, appetite changes, nausea, vomiting, rash, jaundice, thromboembolism, hypertension, liver dysfunction, kidney dysfunction, glucose intolerance, and diabetes.
Trial Locations
- Locations (1)
West China Second University Hospital
🇨🇳Chengdu, Sichuan, China