Back to resultsEffects of GnRHa on Ovarian Function Against Chemotherapy-induced-gonadotoxicity
Primary Purpose
Breast Cancer
Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
GnRHa
Sponsored by
About this trial
This is an interventional prevention trial for Breast Cancer focused on measuring GnRHa, ovarian function, anti-mullerian hormone
Eligibility Criteria
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.
Sites / Locations
- Zhejiang Cancer Hospital
- Shanghai Jiao Tong University Affiliated Sixth People's Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
GnRHa group
None GnRHa group
Arm Description
Eligible patients with breast cancer treated with GnRHa while receiving chemotherapy.
Eligible patients with breast cancer treated without GnRHa while receiving chemotherapy.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Survival Rate
Overall Survival & Tumor Free Survival
Full Information
NCT ID
NCT02518191
First Posted
August 5, 2015
Last Updated
May 14, 2021
Sponsor
Xiangyun Zong
Collaborators
Zhejiang Cancer Hospital
1. Study Identification
Unique Protocol Identification Number
NCT02518191
Brief Title
Effects of GnRHa on Ovarian Function Against Chemotherapy-induced-gonadotoxicity
Official Title
Effects of GnRHa on Ovarian Function Against Chemotherapy-induced-gonadotoxicity in Women With Breast Cancer in China
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
September 1, 2015 (Actual)
Primary Completion Date
January 12, 2021 (Actual)
Study Completion Date
January 12, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Xiangyun Zong
Collaborators
Zhejiang Cancer Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
GnRHa, ovarian function, anti-mullerian hormone
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
345 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GnRHa group
Arm Type
Experimental
Arm Description
Eligible patients with breast cancer treated with GnRHa while receiving chemotherapy.
Arm Title
None GnRHa group
Arm Type
No Intervention
Arm Description
Eligible patients with breast cancer treated without GnRHa while receiving chemotherapy.
Intervention Type
Drug
Intervention Name(s)
GnRHa
Other Intervention Name(s)
goserelin
Intervention Description
3.6mg subcutaneous injection every 28 days.Initiated 1-2 weeks before chemotherapy and ended 4-8 weeks after chemotherapy.
Primary Outcome Measure Information:
Title
Number of Participants With Premature Ovarian Insufficiency
Description
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.
Time Frame
1 years
Secondary Outcome Measure Information:
Title
Survival Rate
Description
Overall Survival & Tumor Free Survival
Time Frame
5 years
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
49 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
XIANGYUN ZONG, MD, PhD
Organizational Affiliation
Shanghai Jiao Tong University affiliated 6th Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Zhejiang Cancer Hospital
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310022
Country
China
Facility Name
Shanghai Jiao Tong University Affiliated Sixth People's Hospital
City
Shanghai
ZIP/Postal Code
200233
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
16545560
Citation
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.
Results Reference
background
PubMed Identifier
12888366
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. doi: 10.1016/s0959-8049(03)00392-7.
Results Reference
background
PubMed Identifier
16087950
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. doi: 10.1200/JCO.2005.05.551. Epub 2005 Aug 8.
Results Reference
background
PubMed Identifier
17512856
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. doi: 10.1016/S0140-6736(07)60778-8.
Results Reference
background
PubMed Identifier
23860520
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.
Results Reference
background
PubMed Identifier
9042122
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. doi: 10.1016/s0022-3476(97)70345-7.
Results Reference
background
PubMed Identifier
16492690
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. doi: 10.1210/jc.2006-0020. Epub 2006 Feb 21.
Results Reference
background
PubMed Identifier
19364956
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.
Results Reference
background
PubMed Identifier
15936554
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. doi: 10.1016/j.ijrobp.2004.11.038.
Results Reference
background
PubMed Identifier
17932880
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. doi: 10.1002/cncr.23071.
Results Reference
background
PubMed Identifier
10554760
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. doi: 10.1016/s1071-5576(99)00028-3.
Results Reference
background
PubMed Identifier
17914074
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. doi: 10.1634/theoncologist.12-9-1044.
Results Reference
background
PubMed Identifier
15117898
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. doi: 10.1093/humrep/deh257. Epub 2004 Apr 29.
Results Reference
background
PubMed Identifier
23614679
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. doi: 10.2174/1389450111314080005.
Results Reference
background
PubMed Identifier
20113967
Citation
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.
Results Reference
background
PubMed Identifier
17307918
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. doi: 10.1530/REP-06-0061.
Results Reference
background
PubMed Identifier
21550044
Citation
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.
Results Reference
background
PubMed Identifier
24462062
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.
Results Reference
background
PubMed Identifier
25738668
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.
Results Reference
background
PubMed Identifier
35691250
Citation
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.
Results Reference
derived
PubMed Identifier
34967844
Citation
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.
Results Reference
derived
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Effects of GnRHa on Ovarian Function Against Chemotherapy-induced-gonadotoxicity
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