Bicalutamide Plus Aromatase Inhibitors in ER(+)/AR(+)/HER2(-) Metastatic Breast Cancer

NCT02910050 | Unknown Phase 2 DMC

• 1 other identifier: SYSU5010-2016
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

This study is aim to evaluate the efficacy and safety of bicalutamide and aromatase inhibitor in ER(+)/AR(+)/HER2(-) metastatic breast cancer patients who have disease progression after treatment of an aromatase inhibitor.

Conditions

Breast Cancer

Keywords

androgen receptor; bicalutamide; aromatase inhibitors; advanced breast cancer; letrozole; anastrozole; exemestane

Outcome Measures

Primary Outcomes (1)

• clinical benefit rate（CBR）

  Response and progression will be evaluated using RECIST 1.1. Evaluation will occur every 2 months for the first 6 months and then every 3 months till progression or termination of the study.CBR is defined as ratio of participants who have stable disease for over 24 weeks.

  24 weeks

Secondary Outcomes (3)

• progression free survival

  baseline up to approximately 6 months

• objective response rate of bicalutamide plus another AI in participants with measurable disease

  24 weeks

• tolerability of bicalutamide plus an Aromatase inhibitor

  2 years

Study Arms (1)

bicalutamide+ Aromatase Inhibitor

EXPERIMENTAL

ER(+)/AR(+)/HER2(+) metastatic breast cancer patients that previously treated by an aromatase inhibitor

Drug: Bicalutamide; Drug: Aromatase Inhibitor

Interventions

Bicalutamide DRUG

50mg once a day orally

Also known as: Casodex

bicalutamide+ Aromatase Inhibitor

Aromatase Inhibitor DRUG

participants will receive any kind of aromatase inhibitor which has not been received before (steroidal AI change to nonsteroidal AI and vice versa), Letrozole 2.5mg once a day orally, Anastrozole 1mg once a day orally, Exemestane 25mg once a day orally

Also known as: letrozole, anastrozole, exemestane

bicalutamide+ Aromatase Inhibitor

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically confirmed estrogen receptor positive, androgen positive and HER2 negative breast cancer
• Metastatic or unresectable locally advanced disease
• Age over 18 years
• Postmenopausal status （continuous using luteinizing hormone releasing hormone(LHRH) analogue is available）
• Patient must have disease progression after treatment of an Aromatase inhibitor.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS)0-2
• Life expectancy over 3 months.
• Measurable disease according to RECIST version 1.1 or only bone metastasis
• Adequate hematological, hepatic function.
• Voluntarily signed and dated written informed consent prior to any study specific procedure.

You may not qualify if:

• Patient with life-threatening visceral metastasis, such as extensive liver metastasis, brain or meningeal metastasis
• Concomitant diseases/conditions that is not controllable, and Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.
• History of other primary malignancy
• Resistant to steroidal or nonsteroidal aromatase Inhibitor

Sponsors & Collaborators

• Xu fei: lead
• Sun Yat-sen University: collaborator

Study Sites (1)

State Key Laboratory of Oncology in South China,Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Related Publications (13)

• Kuenen-Boumeester V, Van der Kwast TH, Claassen CC, Look MP, Liem GS, Klijn JG, Henzen-Logmans SC. The clinical significance of androgen receptors in breast cancer and their relation to histological and cell biological parameters. Eur J Cancer. 1996 Aug;32A(9):1560-5. doi: 10.1016/0959-8049(96)00112-8.

  PMID: 8911118 BACKGROUND

• Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P, Evans RM. The nuclear receptor superfamily: the second decade. Cell. 1995 Dec 15;83(6):835-9. doi: 10.1016/0092-8674(95)90199-x. No abstract available.

  PMID: 8521507 BACKGROUND

• Grogg A, Trippel M, Pfaltz K, Ladrach C, Droeser RA, Cihoric N, Salhia B, Zweifel M, Tapia C. Androgen receptor status is highly conserved during tumor progression of breast cancer. BMC Cancer. 2015 Nov 9;15:872. doi: 10.1186/s12885-015-1897-2.

  PMID: 26552477 BACKGROUND

• Brys M. Androgens and androgen receptor: do they play a role in breast cancer? Med Sci Monit. 2000 Mar-Apr;6(2):433-8.

  PMID: 11208351 BACKGROUND

• Witzel I, Graeser M, Karn T, Schmidt M, Wirtz R, Schutze D, Rausch A, Janicke F, Milde-Langosch K, Muller V. Androgen receptor expression is a predictive marker in chemotherapy-treated patients with endocrine receptor-positive primary breast cancers. J Cancer Res Clin Oncol. 2013 May;139(5):809-16. doi: 10.1007/s00432-013-1382-8. Epub 2013 Feb 8.

  PMID: 23392859 BACKGROUND

• Fujii R, Hanamura T, Suzuki T, Gohno T, Shibahara Y, Niwa T, Yamaguchi Y, Ohnuki K, Kakugawa Y, Hirakawa H, Ishida T, Sasano H, Ohuchi N, Hayashi S. Increased androgen receptor activity and cell proliferation in aromatase inhibitor-resistant breast carcinoma. J Steroid Biochem Mol Biol. 2014 Oct;144 Pt B:513-22. doi: 10.1016/j.jsbmb.2014.08.019. Epub 2014 Aug 29.

  PMID: 25178713 BACKGROUND

• Ciupek A, Rechoum Y, Gu G, Gelsomino L, Beyer AR, Brusco L, Covington KR, Tsimelzon A, Fuqua SA. Androgen receptor promotes tamoxifen agonist activity by activation of EGFR in ERalpha-positive breast cancer. Breast Cancer Res Treat. 2015 Nov;154(2):225-37. doi: 10.1007/s10549-015-3609-7. Epub 2015 Oct 20.

  PMID: 26487496 BACKGROUND

• Cuenca-Lopez MD, Montero JC, Morales JC, Prat A, Pandiella A, Ocana A. Phospho-kinase profile of triple negative breast cancer and androgen receptor signaling. BMC Cancer. 2014 Apr 30;14:302. doi: 10.1186/1471-2407-14-302.

  PMID: 24779793 BACKGROUND

• Garay JP, Karakas B, Abukhdeir AM, Cosgrove DP, Gustin JP, Higgins MJ, Konishi H, Konishi Y, Lauring J, Mohseni M, Wang GM, Jelovac D, Weeraratna A, Sherman Baust CA, Morin PJ, Toubaji A, Meeker A, De Marzo AM, Lewis G, Subhawong A, Argani P, Park BH. The growth response to androgen receptor signaling in ERalpha-negative human breast cells is dependent on p21 and mediated by MAPK activation. Breast Cancer Res. 2012 Feb 9;14(1):R27. doi: 10.1186/bcr3112.

  PMID: 22321971 BACKGROUND

• Tarulli GA, Butler LM, Tilley WD, Hickey TE. Bringing androgens up a NOTCH in breast cancer. Endocr Relat Cancer. 2014 Aug;21(4):T183-202. doi: 10.1530/ERC-14-0248. Epub 2014 Jul 7.

  PMID: 25001242 BACKGROUND

• Ueda T, Bruchovsky N, Sadar MD. Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways. J Biol Chem. 2002 Mar 1;277(9):7076-85. doi: 10.1074/jbc.M108255200. Epub 2001 Dec 19.

  PMID: 11751884 BACKGROUND

• Gucalp A, Tolaney S, Isakoff SJ, Ingle JN, Liu MC, Carey LA, Blackwell K, Rugo H, Nabell L, Forero A, Stearns V, Doane AS, Danso M, Moynahan ME, Momen LF, Gonzalez JM, Akhtar A, Giri DD, Patil S, Feigin KN, Hudis CA, Traina TA; Translational Breast Cancer Research Consortium (TBCRC 011). Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic Breast Cancer. Clin Cancer Res. 2013 Oct 1;19(19):5505-12. doi: 10.1158/1078-0432.CCR-12-3327. Epub 2013 Aug 21.

  PMID: 23965901 BACKGROUND

• Lu Q, Xia W, Lee K, Zhang J, Yuan H, Yuan Z, Shi Y, Wang S, Xu F. Bicalutamide plus Aromatase Inhibitor in Patients with Estrogen Receptor-Positive/Androgen Receptor-Positive Advanced Breast Cancer. Oncologist. 2020 Jan;25(1):21-e15. doi: 10.1634/theoncologist.2019-0564. Epub 2019 Aug 21.

  PMID: 31434793 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Bulbo-Spinal Atrophy, X-Linked

Interventions

bicalutamide; Aromatase Inhibitors; Letrozole; Anastrozole; exemestane

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Muscular Atrophy, Spinal; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Motor Neuron Disease; Neuromuscular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Fei Xu, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fei Xu, MD

CONTACT

+86-13711277870; xiawen@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: associate chief physician,associate professor,MD

Study Record Dates

• First Submitted: September 6, 2016
• First Posted: September 21, 2016
• Study Start: January 1, 2016
• Primary Completion: September 1, 2018
• Study Completion: December 1, 2018
• Last Updated: December 22, 2017

Record last verified: 2017-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)