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

Breast Cancer Clinical Trial

Official title:

Effects of GnRHa on Ovarian Function Against Chemotherapy-induced-gonadotoxicity in Women With Breast Cancer in China

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02518191
• Other study ID #: JTU-6H-20150731001
• Status: Completed
• Phase: Phase 3
• Start date: September 1, 2015
• Est. completion date: January 12, 2021

Study information

• Verified date: May 2021
• Source: Shanghai Jiao Tong University Affiliated Sixth People's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 345
• Est. completion date: January 12, 2021
• Est. primary completion date: January 12, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 49 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

• Allergic to active or inactive excipients of GnRHa is an exclusion criterion.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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

Locations

Country	Name	City	State
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Shanghai Jiao Tong University Affiliated Sixth People's Hospital	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Xiangyun Zong	Zhejiang Cancer Hospital

Country where clinical trial is conducted

China, 

References & Publications (19)

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. Epub 2006 Mar 20. — View Citation

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. Review. — View Citation

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. Review. — View Citation

Browne HN, Moon KS, Mumford SL, Schisterman EF, Decherney AH, Segars JH, Armstrong AY. Is anti-Müllerian 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. — View Citation

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. Epub 2006 Feb 21. — View Citation

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. Epub 2005 Aug 8. — View Citation

Decanter C, Morschhauser F, Pigny P, Lefebvre C, Gallo C, Dewailly D. Anti-Müllerian 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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Epub 2004 Apr 29. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Survival Rate	Overall Survival & Tumor Free Survival	5 years