Value of LNG-IUS as Fertility-preserving Treatment of EAH and EC

September 3, 2021 updated by: Zheng Ying, West China Second University Hospital

Value of Levonorgestrel-Releasing Intrauterine System (LNG-IUS) in the Fertility-preserving Treatment of Atypical Endometrial Hyperplasia and Early Endometrial Carcinoma

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

224

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Zheng Ying, professor
  • Phone Number: +8613018256012
  • Email: 935398163@qq.com

Study Contact Backup

  • Name: CHEN Si Jing, postgraduate
  • Phone Number: +86218380361314
  • Email: Zhy_chd@126.com

Study Locations

  • China
    • Sichuan
      • Chengdu, Sichuan, China, 610000
        • Recruiting
        • West China Second University Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 40 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

For Patients With Endometrial Cancer：

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: MPA for EC without progesterone contraindication
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.
Drug: Progesterone
MPA oral 250mg-500mg qd for 3 months per cycle
Other Names:
  • medroxyprogesterone acetate (MPA)
Experimental: MPA+Mirena® for EC without contraindication
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.
Drug: Progesterone
MPA oral 250mg-500mg qd for 3 months per cycle
Other Names:
  • medroxyprogesterone acetate (MPA)
Device: Mirena®
levonorgestrel intrauterine sustained release system (LNG-IUS) placed in uterus for 3 months per cycle
Other Names:
  • LNG-IUS
Experimental: Mirena® for EC without contraindication
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.
Device: Mirena®
levonorgestrel intrauterine sustained release system (LNG-IUS) placed in uterus for 3 months per cycle
Other Names:
  • LNG-IUS
Active Comparator: GnRH agonist+Mirena® for EC with contraindication
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.
Device: Mirena®
levonorgestrel intrauterine sustained release system (LNG-IUS) placed in uterus for 3 months per cycle
Other Names:
  • LNG-IUS
Drug: GnRH agonist
GnRH-a intramuscular injection 3.75mg once a month for 3 months per cycle
Other Names:
  • GnRH-a
Experimental: Mirena® for EC with contraindication
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.
Device: Mirena®
levonorgestrel intrauterine sustained release system (LNG-IUS) placed in uterus for 3 months per cycle
Other Names:
  • LNG-IUS
Active Comparator: Mirena® for EAH without progesterone contraindication
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.
Device: Mirena®
levonorgestrel intrauterine sustained release system (LNG-IUS) placed in uterus for 3 months per cycle
Other Names:
  • LNG-IUS
Experimental: MPA for EAH without progesterone contraindication
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.
Drug: Progesterone
MPA oral 250mg-500mg qd for 3 months per cycle
Other Names:
  • medroxyprogesterone acetate (MPA)
Active Comparator: Mirena® for EAH with progesterone contraindication
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.
Device: Mirena®
levonorgestrel intrauterine sustained release system (LNG-IUS) placed in uterus for 3 months per cycle
Other Names:
  • LNG-IUS
Experimental: GnRH-a+Mirena® for EAH with progesterone contraindication
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.
Device: Mirena®
levonorgestrel intrauterine sustained release system (LNG-IUS) placed in uterus for 3 months per cycle
Other Names:
  • LNG-IUS
Drug: GnRH agonist
GnRH-a intramuscular injection 3.75mg once a month for 3 months per cycle
Other Names:
  • GnRH-a

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathologic Response
Time Frame: 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.
6-12 months
Pregnancy Rate
Time Frame: 7-144 months
The percentage of successful pregnancies in the CR patients.
7-144 months
Live Birth Rate
Time Frame: 16-144 months
The percentage of successfully alive baby delivery in the pregnant patients.
16-144 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Side-Affects Rate
Time Frame: 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.
1-144 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

West China Second University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2018

Primary Completion (Anticipated)

December 30, 2025

Study Completion (Anticipated)

December 30, 2030

Study Registration Dates

First Submitted

March 4, 2018

First Submitted That Met QC Criteria

March 12, 2018

First Posted (Actual)

March 13, 2018

Study Record Updates

Last Update Posted (Actual)

September 13, 2021

Last Update Submitted That Met QC Criteria

September 3, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZHENG Ying

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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