Tucidinostat and Fulvestrant in Hormone-receptor Positive Advanced Breast Cancer

Breast Cancer Clinical Trial

Official title:

Trial of Tucidinostat in Combination With Fulvestrant in Patients With Hormone-receptor Positive Advanced Breast Cancer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04999540
• Other study ID #: GDWCH-001
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: November 1, 2021
• Est. completion date: December 30, 2024

Study information

• Verified date: August 2021
• Source: Guangdong Women and Children Hospital
• Contact: Anqin Zhang
• Phone: 020-39151519
• Email: sfyrxzx[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 73
• Est. completion date: December 30, 2024
• Est. primary completion date: December 1, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Tucidinostat
30 mg, administered orally twice per week (BIW)
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Guangdong Women and Children Hospital

References & Publications (10)

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. Review. — View Citation

Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, Park IH, Trédan 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. — View Citation

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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Turner NC, Ro J, André 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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	PFS was defined as the time from treatment until objective disease progression according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1), or death by any cause, whichever is first met.	From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years.
Secondary	overall survival (OS)	Defined as from the date of treatment to date of death, irrespective of cause.	Time from treatment to death from any cause, assessed up to 3 years.
Secondary	Objectivel response rate (ORR)	Defined as numbers of patients achieved complete response and partial response of treatment.	Response is assessed once every 8 weeks, from the day of treatment to the date of first documented progression, assessed up to 3 years.
Secondary	Duration of response (DOR)	Defined as from the first date when criteria for response is met until the first date when the criteria for progression or death is met.	From the day of treatment to the date of first documented progression, assessed up to 3 years.
Secondary	4.Clinical Benefit Rate (CBR)	ORR is defined as percentage of participants with Complete Response, Partial Response or Stable Disease=24 weeks, assessed by the investigators according to the RECIST v1.1.	From the day of treatment to the date of first documented progression, assessed up to 3 years.
Secondary	Adverse event(AE)	Adverse event related to treatment.	From the day of treatment to the date of first documented progression, assessed up to 3 years.