Tucidinostat and Fulvestrant in Hormone-receptor Positive Advanced Breast Cancer

NCT ID: NCT04999540

Last Updated: 2021-08-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

73 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-01

Study Completion Date

2024-12-30

Brief Summary

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The purpose of the study is evaluate the efficacy and safety of tucidinostat in combination with fulvestrant in patients with hormone-receptor positive advanced breast cancer.

Detailed Description

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Hormone-receptor positive breast cancer is the most common subtype in breast cancer. Tucidinostat is an oral subtype-selective histone deacetylase inhibitor, which showed preliminary signs of encouraging anti-tumour activity in patients with advanced hormone-receptor positive breast cancer in the previous studies. The aim of this study is to evaluate the efficacy and safety of Tucidinostat in combination with fulvestrant in patients with recurrent or metastatic hormone-receptor positive breast cancer.

Conditions

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Breast Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Tucidinostat + Fulvestrant

Patients receive 30 mg Chidamide twice per week. Fulvestrant 500mg (2 syringes of Fulvestrant 250mg), Fulvestrant 500 mg i.m. every 28 (+/- 3) days plus an additional 500 mg on day 14 (+/-3) of first month only.

Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Tucidinostat

Intervention Type DRUG

30 mg, administered orally twice per week (BIW)

Fulvestrant

Intervention Type DRUG

Fulvestrant was supplied as a castor oil based solution in clear neutral glass pre-filled syringes. Each syringe will contain 250 mg of fulvestrant in 5 ml.

Interventions

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Tucidinostat

30 mg, administered orally twice per week (BIW)

Intervention Type DRUG

Fulvestrant

Fulvestrant was supplied as a castor oil based solution in clear neutral glass pre-filled syringes. Each syringe will contain 250 mg of fulvestrant in 5 ml.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Female patients aged 18-75 years (including cutoff value);
2. The disease condition is inoperable, recurrent breast cancer, or metastatic breast cancer;
3. Histological or cytological confirmation of hormone receptor-positive \[estrogen receptor (ER) positive and progesterone receptors (PgR) positive or negative\] breast cancer;
4. At least one measurable lesion according to RECIST 1.1;
5. Prior treatment: have not received systemic chemotherapy for recurrent or metastatic breast cancer;
6. Eastern Cooperative Oncology Group Performance Status of 0-1;
7. Adequate function of major organs meets the following requirements):

Absolute Neutrophils count≥ 1.5×10\^9/L; Platelets count≥ 90×10\^9/L; Hemoglobin ≥ 90g/L; Total bilirubin≤ 1.5 × the upper limit of normal (ULN); ALT and AST ≤ 2.5 × ULN; BUN and Cr ≤ 1.5 × ULN; Left ventricular ejection fraction (LVEF) ≥ 50%; QTcF(Fridericia correction) ≤ 470 ms; International normalized ratio(INR)≤1.5 × ULN; activated partial thromboplastin time(APTT) ≤ 1.5 × ULN;
8. Life expectancy ≥ 3 months;
9. Have signed informed consent.

Exclusion Criteria

1. Patients have untreated central nervous system (CNS) metastases;
2. Patients with no measurable lesion according to RECIST 1.1;
3. Patients with bilateral breast cancer;
4. Patients with human epidermal growth factor receptor-2 (Her-2) positive;
5. Recurrent or metastatic disease occurs within 2 years during adjuvant endocrine therapy;
6. Patients previously received systemic chemotherapy for recurrent or metastatic breast cancer;
7. Patients previously received any HDAC inhibitor or fulvestrant treatment;
8. There are ascites, pleural effusion, pericardial effusion with clinical symptoms at baseline, those who need drainage, or those who have undergone drainage of serous effusion within 4 weeks before the first dose;
9. Inability to swallow, intestinal obstruction or other factors affecting the administration and absorption of the drug;
10. Patients with other invasive malignancies within 5 years or at the same time, with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ;
11. Patients with a history of allergies to the drug components of this regimen;
12. Patients with active HBV and HCV infection; stable hepatitis B after drug treatment (HBV virus copy number is higher than the upper limit of reference value) and cured hepatitis C patients (HCV virus copy number exceeds the lower limit of detection method) can be included;
13. Patients with a history of immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency disease, history of organ transplantation;
14. Patients have uncontrolled or significant cardiovascular disease, including: Myocardial infarction (\< the last 12 months); Uncontrolled angina (\< the last 6 months); Congestive heart failure (\< the last 6 months), or Left Ventricular Ejection Fraction (LVEF) \< 50% prior to study entry;
15. Any mental or cognitive disorder, that would interfere the ability to understand the informed consent document or the operation and compliance of study;
16. Any other condition which is inappropriate for the study in the opinion of the investigators.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Guangdong Women and Children Hospital

OTHER

Sponsor Role lead

Responsible Party

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Anqin Zhang

Chief Physician

Responsibility Role PRINCIPAL_INVESTIGATOR

Central Contacts

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Anqin Zhang

Role: CONTACT

020-39151519

References

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Osborne CK, Schiff R. Mechanisms of endocrine resistance in breast cancer. Annu Rev Med. 2011;62:233-47. doi: 10.1146/annurev-med-070909-182917.

Reference Type BACKGROUND
PMID: 20887199 (View on PubMed)

Saxena NK, Sharma D. Epigenetic Reactivation of Estrogen Receptor: Promising Tools for Restoring Response to Endocrine Therapy. Mol Cell Pharmacol. 2010;2(5):191-202.

Reference Type BACKGROUND
PMID: 21499573 (View on PubMed)

Turner NC, Ro J, Andre F, Loi S, Verma S, Iwata H, Harbeck N, Loibl S, Huang Bartlett C, Zhang K, Giorgetti C, Randolph S, Koehler M, Cristofanilli M; PALOMA3 Study Group. Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2015 Jul 16;373(3):209-19. doi: 10.1056/NEJMoa1505270. Epub 2015 Jun 1.

Reference Type BACKGROUND
PMID: 26030518 (View on PubMed)

Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, Park IH, Tredan O, Chen SC, Manso L, Freedman OC, Garnica Jaliffe G, Forrester T, Frenzel M, Barriga S, Smith IC, Bourayou N, Di Leo A. MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. J Clin Oncol. 2017 Nov 10;35(32):3638-3646. doi: 10.1200/JCO.2017.75.6155. Epub 2017 Oct 2.

Reference Type BACKGROUND
PMID: 28968163 (View on PubMed)

Falkenberg KJ, Johnstone RW. Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nat Rev Drug Discov. 2014 Sep;13(9):673-91. doi: 10.1038/nrd4360. Epub 2014 Aug 18.

Reference Type BACKGROUND
PMID: 25131830 (View on PubMed)

Jones PA, Issa JP, Baylin S. Targeting the cancer epigenome for therapy. Nat Rev Genet. 2016 Sep 15;17(10):630-41. doi: 10.1038/nrg.2016.93.

Reference Type BACKGROUND
PMID: 27629931 (View on PubMed)

Shi Y, Dong M, Hong X, Zhang W, Feng J, Zhu J, Yu L, Ke X, Huang H, Shen Z, Fan Y, Li W, Zhao X, Qi J, Huang H, Zhou D, Ning Z, Lu X. Results from a multicenter, open-label, pivotal phase II study of chidamide in relapsed or refractory peripheral T-cell lymphoma. Ann Oncol. 2015 Aug;26(8):1766-71. doi: 10.1093/annonc/mdv237. Epub 2015 Jun 23.

Reference Type BACKGROUND
PMID: 26105599 (View on PubMed)

Zhang Q, Wang T, Geng C, Zhang Y, Zhang J, Ning Z, Jiang Z. Exploratory clinical study of chidamide, an oral subtype-selective histone deacetylase inhibitor, in combination with exemestane in hormone receptor-positive advanced breast cancer. Chin J Cancer Res. 2018 Dec;30(6):605-612. doi: 10.21147/j.issn.1000-9604.2018.06.05.

Reference Type BACKGROUND
PMID: 30700929 (View on PubMed)

Jiang Z, Li W, Hu X, Zhang Q, Sun T, Cui S, Wang S, Ouyang Q, Yin Y, Geng C, Tong Z, Cheng Y, Pan Y, Sun Y, Wang H, Ouyang T, Gu K, Feng J, Wang X, Wang S, Liu T, Gao J, Cristofanilli M, Ning Z, Lu X. Tucidinostat plus exemestane for postmenopausal patients with advanced, hormone receptor-positive breast cancer (ACE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Jun;20(6):806-815. doi: 10.1016/S1470-2045(19)30164-0. Epub 2019 Apr 27.

Reference Type BACKGROUND
PMID: 31036468 (View on PubMed)

Sabnis GJ, Goloubeva OG, Kazi AA, Shah P, Brodie AH. HDAC inhibitor entinostat restores responsiveness of letrozole-resistant MCF-7Ca xenografts to aromatase inhibitors through modulation of Her-2. Mol Cancer Ther. 2013 Dec;12(12):2804-16. doi: 10.1158/1535-7163.MCT-13-0345. Epub 2013 Oct 3.

Reference Type BACKGROUND
PMID: 24092810 (View on PubMed)

Other Identifiers

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GDWCH-001

Identifier Type: -

Identifier Source: org_study_id

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