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

NCT02482753 | Completed Phase 3 DMC

• 1 other identifier: CDM301
• Study Type: interventional
• Target: 365
• Locations: 1 country
• Sites: 22

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.

Conditions

Breast Cancer

Keywords

Chidamide; breast cancer; exemestane; Estrogen Receptor

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• 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 Outcomes (5)

• overall survival, double-blinded period

  Time from randomization to death from any cause, assessed up to 6 years

• duration of response (DOR), double-blinded period

  From the first date of response until the date of first documented progression, assessed up to 3years

• objective response rate (ORR), open-label period and double-blinded period

  Response is assessed once every 6 weeks, assessed up to 3 years

• clinical benefit rate (CBR), open-label period and double-blinded period

  Response is assessed once every 6 weeks, assessed up to 3 years

• PFS, open-label period

  Time from the start of treatment to the earliest of documented disease progression, or death, assessed up to 3 years

Study Arms (3)

Chidamide + exemestane, open-label

EXPERIMENTAL

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.

Drug: Chidamide; Drug: exemestane

Chidamide + exemestane, double-blinded

EXPERIMENTAL

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.

Drug: Chidamide; Drug: exemestane

placebo + exemestane, double-blinded

PLACEBO COMPARATOR

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.

Drug: exemestane; Drug: placebo

Interventions

Chidamide DRUG

30 mg, administered orally twice per week (BIW)

Also known as: CS055

Chidamide + exemestane, double-blinded; Chidamide + exemestane, open-label

exemestane DRUG

25 mg, PO daily

Also known as: Aromasin

Chidamide + exemestane, double-blinded; Chidamide + exemestane, open-label; placebo + exemestane, double-blinded

placebo DRUG

Administered orally twice per week (BIW)

Also known as: Simulation tablet of Chidamide

placebo + exemestane, double-blinded

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \~ 75 years old, postmenopausal women;
• Histological or cytological confirmation of hormone receptor-positive \[estrogen receptor (ER) positive and progesterone receptors (PgR) positive or negative\] breast cancer;
• Disease progression or recurrence after at least one endocrine therapy (either in advanced/metastatic setting or adjuvant setting);
• ≤4 prior therapies (either in advanced/metastatic setting or adjuvant setting), patients may have received one prior chemotherapy;
• The disease condition is inoperable, stage III or stage IV, at least one measurable lesion or simple bone metastases with no measurable lesions;
• 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;
• Eastern Cooperative Oncology Group Performance Status: 0\~1;
• Absolute neutrophil count ≥ 1.5×109 / L, platelet count ≥ 100×109 / L, hemoglobin ≥ 90 g/L;
• Life expectancy ≥ 3 months;
• Have signed informed consent.

You may not qualify if:

• Patients have known central nervous system (CNS) metastases or a history of CNS metastases , or with leptomeningeal disease;
• Patients with human epidermal growth factor receptor-2 (Her-2) positive;
• Patients previously received treatment with exemestane;
• Patients received radiotherapy ≤ 4 weeks prior to study entry;
• Patients with no measurable lesion (except simple bone metastasis), such as pleural or pericardial effusion, ascites, et al;
• 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
• History of any significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or TdP)
• History of significant QT interval prolongation, or Corrected QT Interval (QTc) \> 450 ms prior to study entry
• History of cerebrovascular accident
• Symptomatic coronary heart disease requiring treatment with agents
• The size of fluid area detected by cardiac ultrasonography in cavum pericardium is ≥10mm during diastolic period;
• History of organ transplantation;

Sponsors & Collaborators

• Chipscreen Biosciences, Ltd.: lead

Study Sites (22)

Anhui Provincial Hospital

Hefei, Anhui, 230001, China

Location

The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, 230022, China

Location

The 307th Hospital of Chinese people's Liberation Army

Beijing, Beijing Municipality, 100021, China

Location

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100036, China

Location

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

Location

Cangzhou Central Hospital

Cangzhou, Hebei, 061001, China

Location

Tumor Hospital of Hebei Province

Shijiazhuang, Hebei, 050019, China

Location

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150081, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

Location

Hunan Cancer Hospital

Changsha, Hunan, China

Location

Zhejiang Cancer Hospital

Hangzhou, Jiangsu, 310022, China

Location

Jiangsu Cancer Hospital

Nanjing, Jiangsu, 210009, China

Location

Jiangsu Province Hospital

Nanjing, Jiangsu, 210029, China

Location

The Third Hospital of Nanchang

Nanchang, Jiangxi, 330009, China

Location

Jilin Cancer Hospital

Changchun, Jilin, 130012, China

Location

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

Liaoning Cancer Hospital & Institute

Shenyang, Liaoning, 110042, China

Location

Jinan Central Hospital

Jinan, Shandong, 250013, China

Location

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

Location

Fudan University ZhongShan Hospital

Shanghai, Shanghai Municipality, 200032, China

Location

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, 300060, China

Location

Related Publications (1)

• 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.

  PMID: 31036468 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide; exemestane

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Zefei Jiang

  307 Hospital of PLA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2015
• First Posted: June 26, 2015
• Study Start: July 1, 2015
• Primary Completion: March 1, 2018
• Study Completion: February 1, 2021
• Last Updated: January 12, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (22)