AR-inhibitor Bicalutamide in Treating Patients With TNBC

NCT02353988 | Unknown Phase 2 DMC

• 1 other identifier: JinlingH-001
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

Growing studies demonstrated that Androgen Receptor (AR) has an oncogenic role for the patients with AR-positive Triple Negative Breast Cancer (TNBC). AR antagonists in therapy, such as bicalutamide, completely binds to the AR, increasing AR degradation, thus are investigated for the efficacy of the treatment of patients with AR-positive TNBC in the study.

Conditions

Breast Neoplasms

Keywords

AR-positive; Androgen Antagonists; Bicalutamide; TNBC; metastatic

Outcome Measures

Primary Outcomes (2)

• Clinical benefit rate(CBR)

  The proportion of stability, partial response and complete response in patients who receive bicalutamide as second-, or third-line therapy for estrogen receptor (ER)/ progesterone receptor (PgR)-negative, human epidermal growth factor receptor (HER-2)-negative and AR-positive Metastatic Breast Cancer

  1 Year

• Progression-free survival

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months

Secondary Outcomes (2)

• Quality of life

  1 Year

• Number of adverse events (AE) and serious adverse events (SAE) during the course of the study

  1 Year

Study Arms (2)

bicalutamide

EXPERIMENTAL

This is a multi-center, open-label, phase II study to evaluate the anti-tumor activity and safety of bicalutamide administered orally daily to patients with estrogen receptor (ER)-negative/ progesterone receptor (PgR)-negative/ androgen receptor (AR)-positive metastatic breast cancer. Eligible patients will receive bicalutamide at a dose of 150mg PO daily.

Drug: Bicalutamide

Physician's Choice

ACTIVE COMPARATOR

Treatment of the Physician's Choice defined as any single agent chemotherapy, hormonal treatment or biological therapy approved for the treatment of cancer; or palliative treatment or radiotherapy, administered according to local practice, if applicable

Other: Physician's Choice

Interventions

Bicalutamide DRUG

Patients in experimental group are designated to take bicalutamide orally, 150mg on a continuous schedule. The investigator should pay attention to the patients' adverse event. Every month, the patients will be evaluated for the adverse event by the criterion National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 3.0. Every 2 months, the patients will be evaluated for the clinical effects. If disease progressed, the patients would be ruled out. Treatment continued until disease progression, unacceptable toxic effects, patient or physician request to discontinue, or serious protocol non-compliance. A maximum of 2 dose reductions for grade \>= 3 toxicity were allowed (100 and 50 mg). A maximum of 2 weeks was permitted for treatment delays due to toxicity.

Also known as: immunohistochemistry staining method

bicalutamide

Physician's Choice OTHER

The comparator group, treatment of physician's choice (TPC), represented a mix of agents (both approved and non-approved for metastatic breast cancer) to mirror clinical practice at the time in this setting. The 60 patients are enrolled in the study, before randomized to the two arms, each of them will be assessed for eligibility and then their proposed TPC. Treatment continued until disease progression, unacceptable toxic effects, patient or physician request to discontinue, or serious protocol non-compliance.

Physician's Choice

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients with histologically or cytologically confirmed carcinoma of the breast. Every effort should be made to make paraffin embedded tissue or slides from the diagnostic biopsy or surgical specimen available for confirmation of diagnosis.
• Receptor status: Estrogen receptor- and progesterone receptor-negative,HER-2-negative, Androgen receptor-positive\* NOTE: Samples are considered positive if greater than 10% of cell nuclei are immunoreactive.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2. Life expectancy of \>= 3 months.
• Adequate organ and marrow function as defined below:
• leukocytes \>3,000/mL; absolute neutrophil count \>1,500/ml; platelets \>100,000/mL; total bilirubin within normal institutional limits; aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) \<2.5×institutional upper limit of normal (ULN); creatinine within normal institutional limits OR creatinine clearance \>60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
• Patients with metastatic disease progressed after one therapeutic regimen for metastatic disease, and there is no limit for the regimens of prior therapy.
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
• Women of childbearing potential, but using (1) surgically sterile or (2) adequate measures of contraception in the opinion of the Investigator. Peri-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
• Patients have no other malignancy, except breast cancer.
• Patients willing and able to comply with the study protocol for the duration of the study.
• Written informed consent prior to any study-specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice.

You may not qualify if:

• Patients who have received any of the following treatments within four weeks before Bicalutamide or TPC treatment start: chemotherapy, radiation, trastuzumab, hormonal therapy, surgery, or any investigational drug within four weeks.
• Patients with a hypersensitivity to Bicalutamide or selected TPC treatment.
• Women who are pregnant or breast-feeding; women of childbearing potential refuse to use any measures of contraception.
• Patients have active brain metastases or leptomeningeal disease.
• Patients have important organ failure or serious marrow suppression.
• Severe/uncontrolled intercurrent illness/infection.
• Significant cardiovascular impairment (history of congestive heart failure \> New York Heart Association grade II, severe valvular heart disease，unstable angina or myocardial infarction within the past six months, or serious cardiac arrhythmia, or resistant hypertension).
• Patients can't comply with the study protocol for the duration of the study.
• Patients have had a prior malignancy within five years, other than previous breast cancer.
• Participation in another clinical trial with any investigational agents within 3 weeks prior to study screening.
• Patients with known Central Nervous System (CNS) disease (primary or secondary) or leptomeningeal disease because of their poor prognosis and because they often develop progressive neurological dysfunction that would confound the evaluation of neurological and other adverse events.
• Gastrointestinal disorders interfering with absorption of the study drug.
• Difficulties with swallowing study capsules/tablets.
• Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies.

Sponsors & Collaborators

• Jinling Hospital, China: lead
• Wenzhou Medical University: collaborator
• The First People's Hospital of Lianyungang: collaborator
• Wuxi People's Hospital: collaborator
• Nanning Second People's Hospital: collaborator
• Jiangsu Province Hospital of Traditional Chinese Medicine: collaborator
• The Second Hospital of Nanjing Medical University: collaborator

Related Publications (8)

• Hu R, Dawood S, Holmes MD, Collins LC, Schnitt SJ, Cole K, Marotti JD, Hankinson SE, Colditz GA, Tamimi RM. Androgen receptor expression and breast cancer survival in postmenopausal women. Clin Cancer Res. 2011 Apr 1;17(7):1867-74. doi: 10.1158/1078-0432.CCR-10-2021. Epub 2011 Feb 15.

  PMID: 21325075 BACKGROUND

• Robinson JL, Macarthur S, Ross-Innes CS, Tilley WD, Neal DE, Mills IG, Carroll JS. Androgen receptor driven transcription in molecular apocrine breast cancer is mediated by FoxA1. EMBO J. 2011 Jun 24;30(15):3019-27. doi: 10.1038/emboj.2011.216.

  PMID: 21701558 BACKGROUND

• McGhan LJ, McCullough AE, Protheroe CA, Dueck AC, Lee JJ, Nunez-Nateras R, Castle EP, Gray RJ, Wasif N, Goetz MP, Hawse JR, Henry TJ, Barrett MT, Cunliffe HE, Pockaj BA. Androgen receptor-positive triple negative breast cancer: a unique breast cancer subtype. Ann Surg Oncol. 2014 Feb;21(2):361-7. doi: 10.1245/s10434-013-3260-7. Epub 2013 Sep 18.

  PMID: 24046116 BACKGROUND

• Fioretti FM, Sita-Lumsden A, Bevan CL, Brooke GN. Revising the role of the androgen receptor in breast cancer. J Mol Endocrinol. 2014 Jun;52(3):R257-65. doi: 10.1530/JME-14-0030. Epub 2014 Apr 16.

  PMID: 24740738 BACKGROUND

• Shah PD, Gucalp A, Traina TA. The role of the androgen receptor in triple-negative breast cancer. Womens Health (Lond). 2013 Jul;9(4):351-60. doi: 10.2217/whe.13.33.

  PMID: 23826776 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

• Park S, Koo J, Park HS, Kim JH, Choi SY, Lee JH, Park BW, Lee KS. Expression of androgen receptors in primary breast cancer. Ann Oncol. 2010 Mar;21(3):488-492. doi: 10.1093/annonc/mdp510. Epub 2009 Nov 3.

  PMID: 19887463 BACKGROUND

• Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, Pietenpol JA. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011 Jul;121(7):2750-67. doi: 10.1172/JCI45014.

  PMID: 21633166 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

bicalutamide; Immunohistochemistry

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Immunologic Techniques

Central Study Contacts

Xiaoxiang Guan, MD; PhD

CONTACT

+86 13512510329; xguan@nju.edu.cn

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: Bicalutamide in Treating Patients With AR-positive Metastatic Triple Negative Breast Cancer

Study Record Dates

• First Submitted: January 26, 2015
• First Posted: February 3, 2015
• Study Start: January 1, 2015
• Primary Completion: January 1, 2017
• Study Completion: May 1, 2017
• Last Updated: February 3, 2015

Record last verified: 2015-01