Trial of Chidamide in Combination With Exemestane in Patients With Advanced Breast Cancer

Breast Cancer Clinical Trial

Official title:

A Phase III Trial of Chidamide in Combination With Exemestane in Patients With Hormone Receptor-Positive Advanced Breast Cancer (ACE)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02482753
• Other study ID #: CDM301
• Status: Completed
• Phase: Phase 3
• Start date: July 2015
• Est. completion date: February 2021

Study information

• Verified date: January 2022
• Source: Chipscreen Biosciences, Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study was to evaluate the efficacy and safety of Chidamide in combination with exemestane in postmenopausal patients with hormone-receptor positive advanced breast cancer.

Description:

This study including two parts: (1) Part A, open-label design, 20 patients will be enrolled and receive 30 mg Chidamide BIW and 25 mg exemestane QD. The main object of part A is to evaluate the pharmacokinetic and pharmacodynamic profile of Chidamide when in combination with exemestane. (2) Part B, randomized and double-blinded design, 328 patients will be assigned randomly in a 2:1 ratio to experiment group (30 mg Chidamide BIW + 25 mg exemestane QD) and control group (placebo BIW + 25 mg exemestane QD), to evaluate the efficacy and safety of Chidamide when in combination with exemestane in patients with locally advanced or metastatic estrogen receptor-positive breast cancer progressing on endocrine therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 365
• Est. completion date: February 2021
• Est. primary completion date: March 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. 18 ~ 75 years old, postmenopausal women;

2. Histological or cytological confirmation of hormone receptor-positive [estrogen receptor (ER) positive and progesterone receptors (PgR) positive or negative] breast cancer;

3. Disease progression or recurrence after at least one endocrine therapy (either in advanced/metastatic setting or adjuvant setting);

4. =4 prior therapies (either in advanced/metastatic setting or adjuvant setting), patients may have received one prior chemotherapy;

5. The disease condition is inoperable, stage III or stage IV, at least one measurable lesion or simple bone metastases with no measurable lesions;

6. Last prior therapy intervals: (a) if the last treatment was endocrine therapy, the interval must = 2 weeks; (b) if the last treatment was chemotherapy therapy, the interval must = 4 weeks;

7. Eastern Cooperative Oncology Group Performance Status: 0~1;

8. Absolute neutrophil count = 1.5×109 / L, platelet count = 100×109 / L, hemoglobin = 90 g/L;

9. Life expectancy = 3 months;

10. Have signed informed consent.

Exclusion Criteria:

1. Patients have known central nervous system (CNS) metastases or a history of CNS metastases , or with leptomeningeal disease;

2. Patients with human epidermal growth factor receptor-2 (Her-2) positive;

3. Patients previously received treatment with exemestane;

4. Patients received radiotherapy = 4 weeks prior to study entry;

5. Patients with no measurable lesion (except simple bone metastasis), such as pleural or pericardial effusion, ascites, et al;

6. Patients have uncontrolled or significant cardiovascular disease, including:

1. Myocardial infarction (< the last 12 months)

2. Uncontrolled angina (< the last 6 months)

3. Congestive heart failure (< the last 6 months), or Left Ventricular Ejection Fraction (LVEF) < 50% prior to study entry

4. History of any significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or TdP)

5. History of significant QT interval prolongation, or Corrected QT Interval (QTc) > 450 ms prior to study entry

6. History of cerebrovascular accident

7. Symptomatic coronary heart disease requiring treatment with agents

7. The size of fluid area detected by cardiac ultrasonography in cavum pericardium is =10mm during diastolic period;

8. History of organ transplantation;

9. Patients have not recovered from all clinically relevant toxicities to grade 1 due to prior therapies;

10. Patients have clinical significant gastrointestinal abnormality, e.g., unable to swallow, chronic diarrhea, ileus, that would interfere the ingestion,transportation or absorption of oral agents;

11. Active infection [Suffered from active infection of bacteria, virus, fungi, mycobacteria, parasites, or other infections (excluding nail bed fungal infections), or require intravenous antibiotic therapy, or antiviral therapy, or hospitalization due to any significant infection events], or persistent fever within 14 days prior to study entry;

12. Patients had organ surgery < 6 weeks prior to study entry;

13. Abnormal liver function [total bilirubin > 1.5×upper limit of normal (> 3×upper limit of normal in case of Gilbert syndrome); Transaminases (ALT, AST) >2.5×upper limit of normal (>5x upper limit of normal patients with liver metastases), abnormal renal function (serum creatinine > 1.5×upper limit of normal);

14. Patients with prior invasive malignancies with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ, unless received curative treatment and with documented evidence of no recurrence in the past five years;

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. Patients are currently enrolled in another investigational drug study, or completed within 4 weeks prior to study entry, with the exception of patients only in overall survival follow-up;

17. 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:
• Chidamide
30 mg, administered orally twice per week (BIW)
• exemestane
25 mg, PO daily
• placebo
Administered orally twice per week (BIW)

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	The 307th Hospital of Chinese people's Liberation Army	Beijing	Beijing
China	Cangzhou Central Hospital	Cangzhou	Hebei
China	Jilin Cancer Hospital	Changchun	Jilin
China	The First Hospital of Jilin University	Changchun	Jilin
China	Hunan Cancer Hospital	Changsha	Hunan
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	Harbin Medical University Cancer Hospital	Ha'erbin	Heilongjiang
China	Zhejiang Cancer Hospital	Hangzhou	Jiangsu
China	Anhui Provincial Hospital	Hefei	Anhui
China	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	Jinan Central Hospital	Jinan	Shandong
China	The Third Hospital of Nanchang	Nanchang	Jiangxi
China	Jiangsu Cancer Hospital	Nanjing	Jiangsu
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Fudan University ZhongShan Hospital	Shanghai	Shanghai
China	Liaoning Cancer Hospital & Institute	Shenyang	Liaoning
China	Peking University Shenzhen Hospital	Shenzhen	Guangdong
China	Tumor Hospital of Hebei Province	Shijiazhuang	Hebei
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Chipscreen Biosciences, Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	progression-free survival (PFS), double-blinded period	PFS is measured from the date of randomization until progression or death, whichever is first met	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years
Primary	pharmacokinetic profiles of Chidamide, open-label period	The pharmacokinetic parameters include Area under the plasma concentration versus time curve (AUC) , Peak Plasma Concentration (Cmax), time to reach Cmax (Tmax), mean concentration at steady state (Css)	0,1,2,4,8,12,24,48,72 hours after the first dose of Chidamide on day 2 at induced stage (4 days in total); 0,1,2,4,8,12,24,48,72 hours post-dose on day 1 of cycle 1 at combination treatment stage
Primary	pharmacokinetic profiles of exemestane, open-label period	The pharmacokinetic parameters include Area under the plasma concentration versus time curve (AUC) , Peak Plasma Concentration (Cmax), time to reach Cmax (Tmax), mean concentration at steady state (Css)	0,1,2,4,8,12,24 hours after the first dose of exemestane on day 1 at induced stage (4 days in total); 0,1,2,4,8,12,24,48,72 hours post-dose on day 1 of cycle 1 at combination treatment stage
Primary	acetylation level of histone H3, open-label period	The acetylation level of histone H3 is assayed by enzyme-linked immuno sorbent assay (ELISA).	pre-dose of Chidamide on day 2 at induced stage (4 days in total); pre-dose of Chidamide on day 1 of cycle 2 at combination treatment stage
Secondary	overall survival, double-blinded period	OS is measured from the date of randomization until death	Time from randomization to death from any cause, assessed up to 6 years
Secondary	duration of response (DOR), double-blinded period	DOR is measured from the first date when criteria for response is met until the first date when the criteria for progression is met	From the first date of response until the date of first documented progression, assessed up to 3years
Secondary	objective response rate (ORR), open-label period and double-blinded period	ORR is defined as percentage of participants with Complete Response and Partial Response, assessed by the investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST)	Response is assessed once every 6 weeks, assessed up to 3 years
Secondary	clinical benefit rate (CBR), open-label period and double-blinded period	ORR is defined as percentage of participants with Complete Response, Partial Response or Stable Disease = 24 weeks, assessed by the investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST)	Response is assessed once every 6 weeks, assessed up to 3 years
Secondary	PFS, open-label period	PFS is measured from the start of treatment until progression or death, whichever is first met	Time from the start of treatment to the earliest of documented disease progression, or death, assessed up to 3 years