Effects of GnRHa on Ovarian Function Against Chemotherapy-induced-gonadotoxicity

NCT02518191 | Completed Phase 3 Results DMC

• 1 other identifier: JTU-6H-20150731001
• Study Type: interventional
• Target: 345
• Locations: 1 country
• Sites: 2

Brief Summary

This prospective randomized controlled study is conducted to analyze the effect of Goserelin on ovarian function in women with breast cancer in China.

Conditions

Breast Cancer

Keywords

GnRHa; ovarian function; anti-mullerian hormone

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Premature Ovarian Insufficiency

  The serum levels of anti-Müllerian hormone (AMH) were measured using human AMH ELISA kit (11351, Biofine)). POI (premature ovarian insufficiency) was defined as AMH\<0.5ng/mL in this study.

  1 years

Secondary Outcomes (1)

• Survival Rate

  5 years

Study Arms (2)

GnRHa group

EXPERIMENTAL

Eligible patients with breast cancer treated with GnRHa while receiving chemotherapy.

Drug: GnRHa

None GnRHa group

NO INTERVENTION

Eligible patients with breast cancer treated without GnRHa while receiving chemotherapy.

Interventions

GnRHa DRUG

3.6mg subcutaneous injection every 28 days.Initiated 1-2 weeks before chemotherapy and ended 4-8 weeks after chemotherapy.

Also known as: goserelin

GnRHa group

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Premenopausal women 18 to 49 years of age are eligible for enrollment
• Patients have operable stage I to IIIA breast cancer for which treatment with adjuvant or neoadjuvant cyclophosphamide-containing chemotherapy was planned.
• Eligible participants had taken no estrogens, antiestrogens, selective estrogen-receptor modulators, aromatase inhibitors, or hormonal contraceptives within the month before enrollment.
• Human chorionic gonadotropin negative by urine test before entering the group.
• Informed consent, understanding and compliance with the requirements of the study.
• No significant chronic disease and any organ dysfunction.

You may not qualify if:

• Exceptions were made for the use of hormonal contraception in women younger than 35 years of age that was discontinued before randomization.
• Use of hormonal treatment for up to 2 months for the purposes of in vitro fertilization and cryopreservation of embryos or oocytes before randomization.
• Patients with metastatic lesions or history of bilateral ovariectomy,ovarian radiation were excluded.
• Patients received previous adjuvant endocrine therapy for breast cancer are not suitable to this trial.
• Patients with uterine and/or adnexal diseases needing medical or surgical treatment are not suitable.

Sponsors & Collaborators

• Xiangyun Zong: lead
• Zhejiang Cancer Hospital: collaborator

Study Sites (2)

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

Location

Shanghai Jiao Tong University Affiliated Sixth People's Hospital

Shanghai, 200233, China

Location

Related Publications (21)

• Baum M, Hackshaw A, Houghton J, Rutqvist, Fornander T, Nordenskjold B, Nicolucci A, Sainsbury R; ZIPP International Collaborators Group. Adjuvant goserelin in pre-menopausal patients with early breast cancer: Results from the ZIPP study. Eur J Cancer. 2006 May;42(7):895-904. doi: 10.1016/j.ejca.2005.12.013. Epub 2006 Mar 20.

  PMID: 16545560 BACKGROUND

• Kaufmann M, Jonat W, Blamey R, Cuzick J, Namer M, Fogelman I, de Haes JC, Schumacher M, Sauerbrei W; Zoladex Early Breast Cancer Research Association (ZEBRA) Trialists' Group. Survival analyses from the ZEBRA study. goserelin (Zoladex) versus CMF in premenopausal women with node-positive breast cancer. Eur J Cancer. 2003 Aug;39(12):1711-7. doi: 10.1016/s0959-8049(03)00392-7.

  PMID: 12888366 BACKGROUND

• Davidson NE, O'Neill AM, Vukov AM, Osborne CK, Martino S, White DR, Abeloff MD. Chemoendocrine therapy for premenopausal women with axillary lymph node-positive, steroid hormone receptor-positive breast cancer: results from INT 0101 (E5188). J Clin Oncol. 2005 Sep 1;23(25):5973-82. doi: 10.1200/JCO.2005.05.551. Epub 2005 Aug 8.

  PMID: 16087950 BACKGROUND

• LHRH-agonists in Early Breast Cancer Overview group; Cuzick J, Ambroisine L, Davidson N, Jakesz R, Kaufmann M, Regan M, Sainsbury R. Use of luteinising-hormone-releasing hormone agonists as adjuvant treatment in premenopausal patients with hormone-receptor-positive breast cancer: a meta-analysis of individual patient data from randomised adjuvant trials. Lancet. 2007 May 19;369(9574):1711-23. doi: 10.1016/S0140-6736(07)60778-8.

  PMID: 17512856 BACKGROUND

• Yang H, Zong X, Yu Y, Shao G, Zhang L, Qian C, Bian Y, Xu X, Sun W, Meng X, Ding X, Chen D, Zou D, Xie S, Zheng Y, Zhang J, He X, Sun C, Yu X, Ni J. Combined effects of goserelin and tamoxifen on estradiol level, breast density, and endometrial thickness in premenopausal and perimenopausal women with early-stage hormone receptor-positive breast cancer: a randomised controlled clinical trial. Br J Cancer. 2013 Aug 6;109(3):582-8. doi: 10.1038/bjc.2013.324. Epub 2013 Jul 16.

  PMID: 23860520 BACKGROUND

• Sarafoglou K, Boulad F, Gillio A, Sklar C. Gonadal function after bone marrow transplantation for acute leukemia during childhood. J Pediatr. 1997 Feb;130(2):210-6. doi: 10.1016/s0022-3476(97)70345-7.

  PMID: 9042122 BACKGROUND

• Chemaitilly W, Mertens AC, Mitby P, Whitton J, Stovall M, Yasui Y, Robison LL, Sklar CA. Acute ovarian failure in the childhood cancer survivor study. J Clin Endocrinol Metab. 2006 May;91(5):1723-8. doi: 10.1210/jc.2006-0020. Epub 2006 Feb 21.

  PMID: 16492690 BACKGROUND

• Green DM, Sklar CA, Boice JD Jr, Mulvihill JJ, Whitton JA, Stovall M, Yasui Y. Ovarian failure and reproductive outcomes after childhood cancer treatment: results from the Childhood Cancer Survivor Study. J Clin Oncol. 2009 May 10;27(14):2374-81. doi: 10.1200/JCO.2008.21.1839. Epub 2009 Apr 13.

  PMID: 19364956 BACKGROUND

• Wallace WH, Thomson AB, Saran F, Kelsey TW. Predicting age of ovarian failure after radiation to a field that includes the ovaries. Int J Radiat Oncol Biol Phys. 2005 Jul 1;62(3):738-44. doi: 10.1016/j.ijrobp.2004.11.038.

  PMID: 15936554 BACKGROUND

• Oktem O, Oktay K. Quantitative assessment of the impact of chemotherapy on ovarian follicle reserve and stromal function. Cancer. 2007 Nov 15;110(10):2222-9. doi: 10.1002/cncr.23071.

  PMID: 17932880 BACKGROUND

• Blumenfeld Z, Avivi I, Ritter M, Rowe JM. Preservation of fertility and ovarian function and minimizing chemotherapy-induced gonadotoxicity in young women. J Soc Gynecol Investig. 1999 Sep-Oct;6(5):229-39. doi: 10.1016/s1071-5576(99)00028-3.

  PMID: 10554760 BACKGROUND

• Blumenfeld Z. How to preserve fertility in young women exposed to chemotherapy? The role of GnRH agonist cotreatment in addition to cryopreservation of embrya, oocytes, or ovaries. Oncologist. 2007 Sep;12(9):1044-54. doi: 10.1634/theoncologist.12-9-1044.

  PMID: 17914074 BACKGROUND

• Meirow D, Assad G, Dor J, Rabinovici J. The GnRH antagonist cetrorelix reduces cyclophosphamide-induced ovarian follicular destruction in mice. Hum Reprod. 2004 Jun;19(6):1294-9. doi: 10.1093/humrep/deh257. Epub 2004 Apr 29.

  PMID: 15117898 BACKGROUND

• Osborne SE, Detti L. GnRH-analogues for ovarian protection in childhood cancer patients: how adult hypotheses are relevant in prepubertal females. Curr Drug Targets. 2013 Jul;14(8):856-63. doi: 10.2174/1389450111314080005.

  PMID: 23614679 BACKGROUND

• Decanter C, Morschhauser F, Pigny P, Lefebvre C, Gallo C, Dewailly D. Anti-Mullerian hormone follow-up in young women treated by chemotherapy for lymphoma: preliminary results. Reprod Biomed Online. 2010 Feb;20(2):280-5. doi: 10.1016/j.rbmo.2009.11.010. Epub 2009 Dec 3.

  PMID: 20113967 BACKGROUND

• Maltaris T, Beckmann MW, Binder H, Mueller A, Hoffmann I, Koelbl H, Dittrich R. The effect of a GnRH agonist on cryopreserved human ovarian grafts in severe combined immunodeficient mice. Reproduction. 2007 Feb;133(2):503-9. doi: 10.1530/REP-06-0061.

  PMID: 17307918 BACKGROUND

• Browne HN, Moon KS, Mumford SL, Schisterman EF, Decherney AH, Segars JH, Armstrong AY. Is anti-Mullerian hormone a marker of acute cyclophosphamide-induced ovarian follicular destruction in mice pretreated with cetrorelix? Fertil Steril. 2011 Jul;96(1):180-186.e2. doi: 10.1016/j.fertnstert.2011.04.008. Epub 2011 May 7.

  PMID: 21550044 BACKGROUND

• Detti L, Uhlmann RA, Zhang J, Diamond MP, Saed GM, Fletcher NM, Lu M, Williams LJ. Goserelin fosters bone elongation but does not prevent ovarian damage in cyclophosphamide-treated prepubertal mice. Fertil Steril. 2014 Apr;101(4):1157-64.e1. doi: 10.1016/j.fertnstert.2013.12.028. Epub 2014 Jan 23.

  PMID: 24462062 BACKGROUND

• Moore HC, Unger JM, Phillips KA, Boyle F, Hitre E, Porter D, Francis PA, Goldstein LJ, Gomez HL, Vallejos CS, Partridge AH, Dakhil SR, Garcia AA, Gralow J, Lombard JM, Forbes JF, Martino S, Barlow WE, Fabian CJ, Minasian L, Meyskens FL Jr, Gelber RD, Hortobagyi GN, Albain KS; POEMS/S0230 Investigators. Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy. N Engl J Med. 2015 Mar 5;372(10):923-32. doi: 10.1056/NEJMoa1413204.

  PMID: 25738668 BACKGROUND

• Zong X, Yu Y, Chen W, Zong W, Yang H, Chen X. Ovarian reserve in premenopausal women with breast cancer. Breast. 2022 Aug;64:143-150. doi: 10.1016/j.breast.2022.05.009. Epub 2022 Jun 2.

  PMID: 35691250 DERIVED

• Zong X, Yu Y, Yang H, Chen W, Ding X, Liu S, Li X, Chen X, Jiang C, Xia X, Huang R, Zhu M, Hu J, Liang C. Effects of Gonadotropin-Releasing Hormone Analogs on Ovarian Function Against Chemotherapy-Induced Gonadotoxic Effects in Premenopausal Women With Breast Cancer in China: A Randomized Clinical Trial. JAMA Oncol. 2022 Feb 1;8(2):252-258. doi: 10.1001/jamaoncol.2021.6214.

  PMID: 34967844 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Goserelin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: Dr. ZONG
• Organization: Shanghai 6th People's Hospital Affiliated to Shanghai Jiao Tong University

tigerzong@msn.com

86 (21) 24058549

Study Officials

• XIANGYUN ZONG, MD, PhD

  Shanghai Jiao Tong University affiliated 6th Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief

Study Record Dates

• First Submitted: August 5, 2015
• First Posted: August 7, 2015
• Study Start: September 1, 2015
• Primary Completion: January 12, 2021
• Study Completion: January 12, 2021
• Last Updated: June 11, 2021
• Results First Posted: May 3, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)