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

NCT ID: NCT02482753

Last Updated: 2022-01-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 365 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2021-02-28

Brief 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.

Detailed 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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Chidamide + exemestane, open-label

Patients receive 30 mg Chidamide per week and 25 mg exemestane QD. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Chidamide

Intervention Type: DRUG

30 mg, administered orally twice per week (BIW)

exemestane

Intervention Type: DRUG

25 mg, PO daily

Chidamide + exemestane, double-blinded

Patients receive 30 mg Chidamide twice per week and 25 mg exemestane QD. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Chidamide

Intervention Type: DRUG

30 mg, administered orally twice per week (BIW)

exemestane

Intervention Type: DRUG

25 mg, PO daily

placebo + exemestane, double-blinded

Patients receive placebo twice per week and 25 mg exemestane PO QD. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Group Type: PLACEBO_COMPARATOR

exemestane

Intervention Type: DRUG

25 mg, PO daily

placebo

Intervention Type: DRUG

Administered orally twice per week (BIW)

Interventions

Chidamide

30 mg, administered orally twice per week (BIW)

Intervention Type: DRUG

exemestane

25 mg, PO daily

Intervention Type: DRUG

placebo

Administered orally twice per week (BIW)

Intervention Type: DRUG

Other Intervention Names

CS055; Aromasin; Simulation tablet of Chidamide

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Chipscreen Biosciences, Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zefei Jiang

Role: PRINCIPAL_INVESTIGATOR

307 Hospital of PLA

Locations

Anhui Provincial Hospital

Hefei, Anhui, China

The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, China

The 307th Hospital of Chinese people's Liberation Army

Beijing, Beijing Municipality, China

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Peking University Shenzhen Hospital

Shenzhen, Guangdong, China

Cangzhou Central Hospital

Cangzhou, Hebei, China

Tumor Hospital of Hebei Province

Shijiazhuang, Hebei, China

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China

Henan Cancer Hospital

Zhengzhou, Henan, China

Hunan Cancer Hospital

Changsha, Hunan, China

Zhejiang Cancer Hospital

Hangzhou, Jiangsu, China

Jiangsu Cancer Hospital

Nanjing, Jiangsu, China

Jiangsu Province Hospital

Nanjing, Jiangsu, China

The Third Hospital of Nanchang

Nanchang, Jiangxi, China

Jilin Cancer Hospital

Changchun, Jilin, China

The First Hospital of Jilin University

Changchun, Jilin, China

Liaoning Cancer Hospital & Institute

Shenyang, Liaoning, China

Jinan Central Hospital

Jinan, Shandong, China

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Fudan University ZhongShan Hospital

Shanghai, Shanghai Municipality, China

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, China

Countries

China

References

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: DERIVED

PMID: 31036468 (View on PubMed)

Other Identifiers

CDM301

Identifier Type: -

Identifier Source: org_study_id