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Trial record 57 of 3025 for:    China Medicine University Hospital

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

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ClinicalTrials.gov Identifier: NCT03463252
Recruitment Status : Recruiting
First Posted : March 13, 2018
Last Update Posted : April 9, 2018
Sponsor:
Information provided by (Responsible Party):
Zheng Ying, 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.


Condition or disease Intervention/treatment Phase
Endometrial Cancer Atypical Endometrial Hyperplasia Drug: Progesterone Device: Mirena® Drug: GnRH agonist Phase 2 Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 224 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Value of Levonorgestrel-Releasing Intrauterine System (LNG-IUS) in the Fertility-preserving Treatment of Atypical Endometrial Hyperplasia and Early Endometrial Carcinoma
Actual Study Start Date : April 1, 2018
Estimated Primary Completion Date : December 30, 2019
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine


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 Name: 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 Name: medroxyprogesterone acetate (MPA)

Device: Mirena®
levonorgestrel intrauterine sustained release system (LNG-IUS) placed in uterus for 3 months per cycle
Other Name: 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 Name: 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 Name: LNG-IUS

Drug: GnRH agonist
GnRH-a intramuscular injection 3.75mg once a month for 3 months per cycle
Other Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: LNG-IUS

Drug: GnRH agonist
GnRH-a intramuscular injection 3.75mg once a month for 3 months per cycle
Other Name: GnRH-a




Primary Outcome Measures :
  1. Pathologic Response [ Time Frame: 6-9 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.

  2. Pregnancy Rate [ Time Frame: 7-15 months ]
    The percentage of successful pregnancies in the CR patients.

  3. Live Birth Rate [ Time Frame: 16-24 months ]
    The percentage of successfully alive baby delivery in the pregnant patients.


Secondary Outcome Measures :
  1. Side-Affects Rate [ Time Frame: 1-9 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.



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Ages Eligible for Study:   up to 40 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03463252


Contacts
Contact: ZHENG Ying, Professor +8613018256012 935398163@qq.com
Contact: CHEN Si Jing, postgraduate +86218380361314 Zhy_chd@126.com

Locations
China, Sichuan
West China Second University Hospital Recruiting
Chengdu, Sichuan, China, 610000
Contact: Zheng Ying, professor    +8613018256012    935398163@qq.com   
Sponsors and Collaborators
West China Second University Hospital
  Study Documents (Full-Text)

Documents provided by Zheng Ying, West China Second University Hospital:
Informed Consent Form  [PDF] July 6, 2017


Publications:
Chinese Medical Association Department of Gynecologic Oncology., Guidelines on Clinical Fertility-Sparing Treatment of Gynecologic Cancer. Chinese Journal of OBsterics and Gynecology, 2014(4):9-9
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Uterine Neoplasms. Version 2.2017 - April 25, 2017. NCCN.org
Guidelines on Clinical Management of Endometrial Hyperplasia. HKCOG GUIDELINES NUMBER 631 (May 2015)
Reproductive endocrinology group of China Health Industry Management Association for maternal and child health industry branch. consensus conference on endometrial hyperplasia: Diagnosis, treatment and follow-up. Journal of Reproductive Medicine. 2017. 26(10): p. 957-959.
Royal College of Obstetricians and Gynaecologists (RCOG) with the British Society for Gynaecological Endoscopy (BSGE). Management of Endometrial Hyperplasia. Green-top Guideline No. 67. RCOG/BSGE Joint Guideline. London; 2016 (cited 29 March 2016).

Responsible Party: Zheng Ying, Professor/Associate Director/Supervisor of Master Student, West China Second University Hospital
ClinicalTrials.gov Identifier: NCT03463252     History of Changes
Other Study ID Numbers: ZHENG Ying
First Posted: March 13, 2018    Key Record Dates
Last Update Posted: April 9, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Physiological Effects of Drugs
Hyperplasia
Endometrial Neoplasms
Endometrial Hyperplasia
Pathologic Processes
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Diseases
Genital Diseases, Female
Progesterone
Levonorgestrel
Medroxyprogesterone
Medroxyprogesterone Acetate
Deslorelin
Progestins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Contraceptive Agents, Male
Antineoplastic Agents, Hormonal
Antineoplastic Agents