Megestrol Acetate Plus LNG-IUS in Young Women With Endometrial Atypical Hyperplasia

NCT03241888 | Completed Phase 2

• 1 other identifier: 2017-30-1
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

To see if megestrol acetate plus Levonorgestrel-releasing intrauterine system (LNG-IUS) will not be inferior to returning the endometrial tissue to a normal state than megestrol acetate or LNG-IUS alone in patients with endometrial atypical hyperplasia.

Conditions

Atypical Endometrial Hyperplasia

Keywords

Levonorgestrel-releasing intrauterine system; megestrol acetate; Atypical Endometrial Hyperplasia

Outcome Measures

Primary Outcomes (2)

• Pathological response rate

  the proportion of histologic regression from endometrial atypical hyperplasia to benign endometrium

  From date of randomization until the date of CR or date of hysterectomy, whichever came first, assessed up to 12 months

• Pathological response time

  time of histologic regression from endometrial atypical hyperplasia to benign endometrium

  From date of randomization until the date of CR or date of hysterectomy, whichever came first, assessed up to 12 months

Secondary Outcomes (4)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  up to 2 years after the treatment for each patient

• Rate of relapse

  up to 2 years after the treatment for each patient

• Rate of pregnancy

  up to 2 years after the treatment for each patient

• Compliance

  up to 2 years after the treatment for each patient

Other Outcomes (1)

• Economic consequences through study completion

  From date of randomization until the date of CR or date of hysterectomy, whichever came first, assessed up to 12 months

Study Arms (3)

MA

ACTIVE COMPARATOR

Patients will receive megestrol acetate 160 mg by mouth daily for at least 3 months.Then every 3 months, an hysteroscope will be used to evaluate the endometrial condition, and the findings will be recorded.

Drug: Megestrol Acetate

LNG-IUS

ACTIVE COMPARATOR

Patients will receive LNG-IUS insertion for at least 3 months. Then every 3 months, an hysteroscope will be used to evaluate the endometrial condition, and the findings will be recorded.

Device: Levonorgestrel-releasing Intrauterine System(LNG-IUS)

MA+LNG-IUS

EXPERIMENTAL

Patients will receive MA (160mg po qd) plus LNG-IUS insertion for at least 3 months. Then every 3 months, an hysteroscope will be used to evaluate the endometrial condition, and the findings will be recorded.

Drug: Megestrol Acetate; Device: Levonorgestrel-releasing Intrauterine System(LNG-IUS)

Interventions

Megestrol Acetate DRUG

At a dosage of 160 mg/day

Also known as: Megace

MA; MA+LNG-IUS

Levonorgestrel-releasing Intrauterine System(LNG-IUS) DEVICE

Active ingredient: levonorgestrel 52mg. It is a hormone-releasing T-shaped intrauterine system.

Also known as: Mirena Intrauterine Device, Mirena

LNG-IUS; MA+LNG-IUS

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Primarily have a confirmed diagnosis of endometrial atypical hyperplasia based upon hysteroscopy
• Have a desire for remaining reproductive function or uterus
• Need to be able to undergo correlative treatment and follow-up

You may not qualify if:

• Acute liver disease or liver tumor (benign or malignant) or renal dysfunction
• Pregnancy or suspicion of pregnancy
• Have a history of EAH and have disease relapse during Merina insertion
• Under treatment of high-dose progestin therapy more than 3 months in recent 6 months
• Congenital or acquired uterine anomaly including fibroids if they distort the uterine cavity
• Confirmed diagnosis of malignant tumor in genital system
• Acute severe disease such as stroke or heart infarction or a history of thrombosis disease
• Hypersensitivity or contradiction to any component of this product
• Ask for removal of the uterus or other conservative treatment
• Smoker(\>15 cigarettes a day)

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Obstetrics and Gynecology Hospital, Fudan University

Shanghai, Shanghai Municipality, 200011, China

Location

Related Publications (8)

• Gressel GM, Parkash V, Pal L. Management options and fertility-preserving therapy for premenopausal endometrial hyperplasia and early-stage endometrial cancer. Int J Gynaecol Obstet. 2015 Dec;131(3):234-9. doi: 10.1016/j.ijgo.2015.06.031. Epub 2015 Sep 8.

  PMID: 26384790 BACKGROUND

• Park JY, Kim DY, Kim JH, Kim YM, Kim KR, Kim YT, Seong SJ, Kim TJ, Kim JW, Kim SM, Bae DS, Nam JH. Long-term oncologic outcomes after fertility-sparing management using oral progestin for young women with endometrial cancer (KGOG 2002). Eur J Cancer. 2013 Mar;49(4):868-74. doi: 10.1016/j.ejca.2012.09.017. Epub 2012 Oct 13.

  PMID: 23072814 BACKGROUND

• Orbo A, Vereide A, Arnes M, Pettersen I, Straume B. Levonorgestrel-impregnated intrauterine device as treatment for endometrial hyperplasia: a national multicentre randomised trial. BJOG. 2014 Mar;121(4):477-86. doi: 10.1111/1471-0528.12499. Epub 2013 Nov 28.

  PMID: 24286192 BACKGROUND

• Wildemeersch D, Janssens D, Pylyser K, De Wever N, Verbeeck G, Dhont M, Tjalma W. Management of patients with non-atypical and atypical endometrial hyperplasia with a levonorgestrel-releasing intrauterine system: long-term follow-up. Maturitas. 2007 Jun 20;57(2):210-3. doi: 10.1016/j.maturitas.2006.12.004. Epub 2007 Jan 31.

  PMID: 17270370 BACKGROUND

• Montz FJ, Bristow RE, Bovicelli A, Tomacruz R, Kurman RJ. Intrauterine progesterone treatment of early endometrial cancer. Am J Obstet Gynecol. 2002 Apr;186(4):651-7. doi: 10.1067/mob.2002.122130.

  PMID: 11967486 BACKGROUND

• Chen M, Jin Y, Li Y, Bi Y, Shan Y, Pan L. Oncologic and reproductive outcomes after fertility-sparing management with oral progestin for women with complex endometrial hyperplasia and endometrial cancer. Int J Gynaecol Obstet. 2016 Jan;132(1):34-8. doi: 10.1016/j.ijgo.2015.06.046. Epub 2015 Oct 1.

  PMID: 26493012 BACKGROUND

• Xu Z, Yang B, Shan W, Liao J, Shao W, Wu P, Zhou S, Ning C, Luo X, Zhu Q, Zhang H, Ma F, Guan J, Chen X. Comparison of the effect of levonorgestrel-intrauterine system with or without oral megestrol acetate on fertility-preserving treatment in patients with atypical endometrial hyperplasia: A prospective, open-label, randomized controlled phase II study. Gynecol Oncol. 2023 Jul;174:133-141. doi: 10.1016/j.ygyno.2023.05.001. Epub 2023 May 12.

  PMID: 37182434 DERIVED

• Mittermeier T, Farrant C, Wise MR. Levonorgestrel-releasing intrauterine system for endometrial hyperplasia. Cochrane Database Syst Rev. 2020 Sep 6;9(9):CD012658. doi: 10.1002/14651858.CD012658.pub2.

  PMID: 32909630 DERIVED

MeSH Terms

Conditions

Endometrial Hyperplasia

Interventions

Megestrol Acetate

Condition Hierarchy (Ancestors)

Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Megestrol; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 12, 2017
• First Posted: August 8, 2017
• Study Start: July 4, 2017
• Primary Completion: June 18, 2020
• Study Completion: June 18, 2020
• Last Updated: September 26, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: The data are available since the publication of the study paper.
• Access Criteria: The data can be accessed through email request.

Locations

CN (1)