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

Atypical Endometrial Hyperplasia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03241888
• Other study ID #: 2017-30-1
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: July 4, 2017
• Est. completion date: June 18, 2020

Study information

• Verified date: June 2020
• Source: Fudan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

After diagnosed of endometrial atypical hyperplasia (EAH) by hysteroscopy, patients will be enrolled. Age, waist circumstances, blood pressure, basic history of infertility, blood pressure, serum lipid level and side effects will be collected. Blood tests, including fasting blood glucose (FBG), postprandial blood glucose (PBG), fasting insulin (FINS), SHBG, sex hormone levels, blood lipids and anti-müllerian hormone(AMH) will be performed before treatment to evacuate their metabolic conditions.

Patients are randomized to 1 of 3 treatment groups. Patients will receive MA (megestrol acetate) 160 mg by mouth daily for at least 3 months on Arm I. Patients will receive LNG-IUS insertion on Arm II and MA 160 mg plus LNG-IUS insertion on Arm III. Then an hysteroscope will be used to evaluate the endometrial condition every 3 months, and the findings will be recorded. For patients with EAH, complete response (CR) is defined as the reversion of endometrial atypical hyperplasia to proliferative or secretory endometrium; partial response (PR) is defined as regression to simple or complex hyperplasia without atypia; no response (NR) is defined as the persistence of the disease; and progressive disease (PD) is defined as the appearance of endometrial cancer in patients. Continuous therapies will be needed in PR, NR or PD.

After completion of study treatment, 2 months of maintenance treatment will be recommended for patients with CR, and participants will be followed up for 2 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: June 18, 2020
• Est. primary completion date: June 18, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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)

Related Conditions & MeSH terms

• Atypical Endometrial Hyperplasia
• Endometrial Hyperplasia
• Hyperplasia

Intervention

Drug:
• Megestrol Acetate
At a dosage of 160 mg/day

Device:
• Levonorgestrel-releasing Intrauterine System(LNG-IUS)
Active ingredient: levonorgestrel 52mg. It is a hormone-releasing T-shaped intrauterine system.

Locations

Country	Name	City	State
China	Obstetrics and Gynecology Hospital, Fudan University	Shanghai	Shanghai

Sponsors (4)

Lead Sponsor	Collaborator
Fudan University	Shanghai 6th People's Hospital, Shanghai Changning Maternity & Infant Health Hospital, Zhejiang Cancer Hospital

Country where clinical trial is conducted

China, 

References & Publications (6)

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Epub 2007 Jan 31. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Economic consequences through study completion	The investigators will evaluate whether the combination could shorten the therapeutic period, so that bring economic benefits.	From date of randomization until the date of CR or date of hysterectomy, whichever came first, assessed up to 12 months
Primary	Pathological response rate		From date of randomization until the date of CR or date of hysterectomy, whichever came first, assessed up to 12 months
Primary	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	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Common side effects from these drugs include weight gain, vaginal spotting and descent of sexuality. Severe side effects include thrombus and diseases related. The investigators will record any mental or body symptoms and evaluate the correlation.	up to 2 years after the treatment for each patient
Secondary	Rate of relapse		up to 2 years after the treatment for each patient
Secondary	Rate of pregnancy		up to 2 years after the treatment for each patient
Secondary	Compliance	The investigators designed a questionnaire to evaluate the compliance through treatment as side effects of oral megestrol acetate may be more common than LNG-IUS. Self Efficacy, physical activity and social support will be scored (1 to 5) and compared among each arm.	up to 2 years after the treatment for each patient