Gonadotropin-releasing Hormone Agonist (GnRHa) Plus Letrozole In Young Women With Early Endometrial Cancer

NCT05247268 | Recruiting Phase 2

• 1 other identifier: 53211032
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

To see if Gonadotropin-releasing hormone analogue (GnRHa) combined with aromatase inhibitors (AIs) will achieve better complete response rate than megestrol acetate or medroxyprogesterone acetate (MA/MPA) alone as fertility-sparing treatment for patients with early endometrial carcinoma.

Conditions

Endometrial Neoplasm Malignant Stage I

Keywords

early endometrial carcinoma; fertility-preserving treatment; gonadotropin-releasing hormone analogue; aromatase inhibitors

Outcome Measures

Primary Outcomes (1)

• Complete response rates within 16 weeks of treatment

  The cumulative 16-week CR rates will be calculated in two groups

  From date of treatment initiation until the date of CR, assessed up to 16 weeks.

Secondary Outcomes (7)

• Complete response rates within 28 weeks of treatment

  From date of treatment initiation until the date of CR, assessed up to 28 weeks.

• Time to achieve complete response

  From date of treatment initiation until the date of CR or date of hysterectomy,From date of randomization until the date of CR, assessed up to 2 years

• Adverse events

  From date of treatment initiation until the date of CR, assessed up to 2 years

• Quality of life during the treatment accessed by WHOQOL-BREF

  From date of randomization until 12 weeks after treatment is over.

• Relapse rates

  up to 2 years after the treatment for each patient

Study Arms (2)

GnRHa+letrozole

EXPERIMENTAL

Patients will be stratified into BMI≥28kg/m2 group and BMI\<28kg/m2 group. Patients in BMI≥28kg/m2 or BMI\<28kg/m2 group will be randomly assigned (1:1) to GnRHa+letrozole group or MA/MPA group. Patients who will be assigned to GnRHa+letrozole group will receive triprorelin acetate (intramuscular injection of 3.75mg was given 4 weeks apart and the maximum use are 6 courses) plus letrozole (2.5mg oral daily and no more than 24 weeks). Then every 3 months, an hysteroscope will be used to evaluate the endometrial condition, and the findings will be recorded.

Drug: Triprorelin Acetate; Drug: Letrozole 2.5mg

MA/MPA

ACTIVE COMPARATOR

Patients will be stratified into BMI≥28kg/m2 group and BMI\<28kg/m2 group. Patients in BMI≥28kg/m2 or BMI\<28kg/m2 group were randomly assigned (1:1) to GnRHa+letrozole group or MA/MPA group.Patients assigned to MA/MPA group will receive MA/MPA (160 mg oral MA daily or 500 mg oral MPA daily).Then every 3 months, an hysteroscopy will be used to evaluate the endometrial condition, and the findings will be recorded.

Drug: Megestrol Acetate 160 MG Oral Tablet; Drug: Medroxyprogesterone Acetate 500 MG

Interventions

Megestrol Acetate 160 MG Oral Tablet DRUG

At a dosage of 160 mg/day

Also known as: Megestrol Acetate

MA/MPA

Medroxyprogesterone Acetate 500 MG DRUG

At a dosage of 500 mg/day

Also known as: Medroxyprogesterone Acetate

MA/MPA

Triprorelin Acetate DRUG

Intramuscular injection of 3.75mg was given 4 weeks apart and the maximum use are 6 courses

GnRHa+letrozole

Letrozole 2.5mg DRUG

At a dosage of 2.5mg/day and no more than 24 weeks

Also known as: Letrozole

GnRHa+letrozole

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Consent informed and signed
• Primarily have a confirmed diagnosis of early-stage endometrial cancer (endometrioid, grade I, without myometrial inva- sion) ) based upon endometrial biopsy, diagnostic curettage or hysteroscopy
• No signs of suspicious myometrial invasion or extrauterine metastasis by enhanced magnetic resonance imaging (MRI), enhanced computed tomography (CT) or transvaginal ultrasonography (TVUS)
• Have a strong desire for remaining reproductive function or uterus
• Have good compliance and follow-up conditions, and patients are willing to follow up in Obstetrics and Gynecology Hospital of Fudan University in time

You may not qualify if:

• Pathologically confirmed as endometrial cancer with suspicious myometrial invasion or extrauterine metastasis
• Recurrent endometrial cancer
• Combined with severe medical disease or severely impaired liver and kidney function
• Patients with other types of endometrial cancer or other malignant tumors of the reproductive system; patients with breast cancer or other hormone- dependent tumors that cannot be used with progesterone
• Those who require hysterectomy or other methods other than conservative treatment with drugs
• Known or suspected pregnancy
• Contraindication for Medroxyprogesterone Acetate, Megestrol Acetate, Triprorelin Acetate, Letrozole or pregnancy
• Hormone treatment within 3 months before entering the trial;
• Acute severe disease such as stroke or heart infarction or a history of thrombosis disease
• Smoker(\>15 cigarettes a day)

Sponsors & Collaborators

• Fudan University: lead
• Peking Union Medical College Hospital: collaborator

Study Sites (1)

Obstetrics and Gynecology Hospital, Fudan University

Shanghai, 200011, China

RECRUITING

Related Publications (22)

• Zhou H, Cao D, Yang J, Shen K, Lang J. Gonadotropin-Releasing Hormone Agonist Combined With a Levonorgestrel-Releasing Intrauterine System or Letrozole for Fertility-Preserving Treatment of Endometrial Carcinoma and Complex Atypical Hyperplasia in Young Women. Int J Gynecol Cancer. 2017 Jul;27(6):1178-1182. doi: 10.1097/IGC.0000000000001008.

  PMID: 28562472 BACKGROUND

• Rackow BW, Arici A. Endometrial cancer and fertility. Curr Opin Obstet Gynecol. 2006 Jun;18(3):245-52. doi: 10.1097/01.gco.0000193012.11523.c5.

  PMID: 16735822 BACKGROUND

• Trimble CL, Kauderer J, Zaino R, Silverberg S, Lim PC, Burke JJ 2nd, Alberts D, Curtin J. Concurrent endometrial carcinoma in women with a biopsy diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study. Cancer. 2006 Feb 15;106(4):812-9. doi: 10.1002/cncr.21650.

  PMID: 16400639 BACKGROUND

• Corzo C, Barrientos Santillan N, Westin SN, Ramirez PT. Updates on Conservative Management of Endometrial Cancer. J Minim Invasive Gynecol. 2018 Feb;25(2):308-313. doi: 10.1016/j.jmig.2017.07.022. Epub 2017 Aug 3.

  PMID: 28782618 BACKGROUND

• 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

• Baek JS, Lee WH, Kang WD, Kim SM. Fertility-preserving treatment in complex atypical hyperplasia and early endometrial cancer in young women with oral progestin: Is it effective? Obstet Gynecol Sci. 2016 Jan;59(1):24-31. doi: 10.5468/ogs.2016.59.1.24. Epub 2016 Jan 15.

  PMID: 26866032 BACKGROUND

• Gunderson CC, Fader AN, Carson KA, Bristow RE. Oncologic and reproductive outcomes with progestin therapy in women with endometrial hyperplasia and grade 1 adenocarcinoma: a systematic review. Gynecol Oncol. 2012 May;125(2):477-82. doi: 10.1016/j.ygyno.2012.01.003. Epub 2012 Jan 11.

  PMID: 22245711 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

• Yang B, Xu Y, Zhu Q, Xie L, Shan W, Ning C, Xie B, Shi Y, Luo X, Zhang H, Chen X. Treatment efficiency of comprehensive hysteroscopic evaluation and lesion resection combined with progestin therapy in young women with endometrial atypical hyperplasia and endometrial cancer. Gynecol Oncol. 2019 Apr;153(1):55-62. doi: 10.1016/j.ygyno.2019.01.014. Epub 2019 Jan 21.

  PMID: 30674421 BACKGROUND

• Mitsuhashi A, Habu Y, Kobayashi T, Kawarai Y, Ishikawa H, Usui H, Shozu M. Long-term outcomes of progestin plus metformin as a fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer patients. J Gynecol Oncol. 2019 Nov;30(6):e90. doi: 10.3802/jgo.2019.30.e90.

  PMID: 31576686 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

• Ignatov A, Ortmann O. Endocrine Risk Factors of Endometrial Cancer: Polycystic Ovary Syndrome, Oral Contraceptives, Infertility, Tamoxifen. Cancers (Basel). 2020 Jul 2;12(7):1766. doi: 10.3390/cancers12071766.

  PMID: 32630728 BACKGROUND

• Emons G, Schally AV. The use of luteinizing hormone releasing hormone agonists and antagonists in gynaecological cancers. Hum Reprod. 1994 Jul;9(7):1364-79. doi: 10.1093/oxfordjournals.humrep.a138714.

  PMID: 7962452 BACKGROUND

• Grundker C, Volker P, Schulz KD, Emons G. Luteinizing hormone-releasing hormone agonist triptorelin and antagonist cetrorelix inhibit EGF-induced c-fos expression in human gynecological cancers. Gynecol Oncol. 2000 Aug;78(2):194-202. doi: 10.1006/gyno.2000.5863.

  PMID: 10926802 BACKGROUND

• Grundker C, Emons G. The Role of Gonadotropin-Releasing Hormone in Cancer Cell Proliferation and Metastasis. Front Endocrinol (Lausanne). 2017 Aug 4;8:187. doi: 10.3389/fendo.2017.00187. eCollection 2017.

  PMID: 28824547 BACKGROUND

• Azim A, Oktay K. Letrozole for ovulation induction and fertility preservation by embryo cryopreservation in young women with endometrial carcinoma. Fertil Steril. 2007 Sep;88(3):657-64. doi: 10.1016/j.fertnstert.2006.12.068. Epub 2007 Apr 10.

  PMID: 17428480 BACKGROUND

• Barker LC, Brand IR, Crawford SM. Sustained effect of the aromatase inhibitors anastrozole and letrozole on endometrial thickness in patients with endometrial hyperplasia and endometrial carcinoma. Curr Med Res Opin. 2009 May;25(5):1105-9. doi: 10.1185/03007990902860549.

  PMID: 19301987 BACKGROUND

• Minig L, Franchi D, Boveri S, Casadio C, Bocciolone L, Sideri M. Progestin intrauterine device and GnRH analogue for uterus-sparing treatment of endometrial precancers and well-differentiated early endometrial carcinoma in young women. Ann Oncol. 2011 Mar;22(3):643-649. doi: 10.1093/annonc/mdq463. Epub 2010 Sep 28.

  PMID: 20876910 BACKGROUND

• Zhang Z, Huang H, Feng F, Wang J, Cheng N. A pilot study of gonadotropin-releasing hormone agonist combined with aromatase inhibitor as fertility-sparing treatment in obese patients with endometrial cancer. J Gynecol Oncol. 2019 Jul;30(4):e61. doi: 10.3802/jgo.2019.30.e61. Epub 2019 Feb 26.

  PMID: 31074242 BACKGROUND

• Yin J, Ma S, Shan Y, Wang Y, Li Y, Jin Y, Pan L. Risk Factors for Recurrence in Patients with Atypical Endometrial Hyperplasia and Endometrioid Adenocarcinoma after Fertility-Sparing Treatments. Cancer Prev Res (Phila). 2020 Apr;13(4):403-410. doi: 10.1158/1940-6207.CAPR-19-0399. Epub 2020 Feb 3.

  PMID: 32015095 BACKGROUND

• Tock S, Jadoul P, Squifflet JL, Marbaix E, Baurain JF, Luyckx M. Fertility Sparing Treatment in Patients With Early Stage Endometrial Cancer, Using a Combination of Surgery and GnRH Agonist: A Monocentric Retrospective Study and Review of the Literature. Front Med (Lausanne). 2018 Aug 27;5:240. doi: 10.3389/fmed.2018.00240. eCollection 2018.

  PMID: 30211167 BACKGROUND

• McCaig FM, Renshaw L, Williams L, Young O, Murray J, Macaskill EJ, McHugh M, Hannon R, Dixon JM. A study of the effects of the aromatase inhibitors anastrozole and letrozole on bone metabolism in postmenopausal women with estrogen receptor-positive breast cancer. Breast Cancer Res Treat. 2010 Feb;119(3):643-51. doi: 10.1007/s10549-009-0646-0.

  PMID: 19941160 BACKGROUND

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

Megestrol Acetate; Tablets; Medroxyprogesterone Acetate; Letrozole

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; 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; Dosage Forms; Pharmaceutical Preparations; Medroxyprogesterone; Hydroxyprogesterones; Progesterone; Pregnenediones; Pregnenes; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.Dr.

Study Record Dates

• First Submitted: January 16, 2022
• First Posted: February 18, 2022
• Study Start: March 11, 2022
• Primary Completion (Estimated): March 10, 2027
• Study Completion (Estimated): September 10, 2027
• Last Updated: April 6, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will be avaliable since this research being published
• Access Criteria: Institutes or researchers who require the data should contact the principle investigator Prof.Xiaojun Chen via email that after this study being published.

Locations

CN (1)