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

Sponsor
Chipscreen Biosciences, Ltd. (Industry)
Overall Status
Completed
CT.gov ID
NCT02482753
Collaborator
(none)
365
22
3
67.1
16.6
0.2

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
365 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase III Trial of Chidamide in Combination With Exemestane in Patients With Hormone Receptor-Positive Advanced Breast Cancer (ACE)
Actual Study Start Date :
Jul 1, 2015
Actual Primary Completion Date :
Mar 1, 2018
Actual Study Completion Date :
Feb 1, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: Chidamide
30 mg, administered orally twice per week (BIW)
Other Names:
  • CS055
  • Drug: exemestane
    25 mg, PO daily
    Other Names:
  • Aromasin
  • Experimental: 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.

    Drug: Chidamide
    30 mg, administered orally twice per week (BIW)
    Other Names:
  • CS055
  • Drug: exemestane
    25 mg, PO daily
    Other Names:
  • Aromasin
  • Placebo Comparator: 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.

    Drug: exemestane
    25 mg, PO daily
    Other Names:
  • Aromasin
  • Drug: placebo
    Administered orally twice per week (BIW)
    Other Names:
  • Simulation tablet of Chidamide
  • Outcome Measures

    Primary Outcome Measures

    1. progression-free survival (PFS), double-blinded period [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]

      PFS is measured from the date of randomization until progression or death, whichever is first met

    2. pharmacokinetic profiles of Chidamide, open-label period [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]

      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)

    3. pharmacokinetic profiles of exemestane, open-label period [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]

      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)

    4. acetylation level of histone H3, open-label period [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]

      The acetylation level of histone H3 is assayed by enzyme-linked immuno sorbent assay (ELISA).

    Secondary Outcome Measures

    1. overall survival, double-blinded period [Time from randomization to death from any cause, assessed up to 6 years]

      OS is measured from the date of randomization until death

    2. duration of response (DOR), double-blinded period [From the first date of response until the date of first documented progression, assessed up to 3years]

      DOR is measured from the first date when criteria for response is met until the first date when the criteria for progression is met

    3. objective response rate (ORR), open-label period and double-blinded period [Response is assessed once every 6 weeks, assessed up to 3 years]

      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)

    4. clinical benefit rate (CBR), open-label period and double-blinded period [Response is assessed once every 6 weeks, assessed up to 3 years]

      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)

    5. PFS, open-label period [Time from the start of treatment to the earliest of documented disease progression, or death, assessed up to 3 years]

      PFS is measured from the start of treatment until progression or death, whichever is first met

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    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:

    7. Myocardial infarction (< the last 12 months)

    8. Uncontrolled angina (< the last 6 months)

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

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

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

    12. History of cerebrovascular accident

    13. Symptomatic coronary heart disease requiring treatment with agents

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

    15. History of organ transplantation;

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

    17. 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;

    18. 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;

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

    20. 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);

    21. 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;

    22. Any mental or cognitive disorder, that would interfere the ability to understand the informed consent document or the operation and compliance of study;

    23. 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;

    24. Any other condition which is inappropriate for the study in the opinion of the investigators.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Anhui Provincial Hospital Hefei Anhui China 230001
    2 The First Affiliated Hospital of Anhui Medical University Hefei Anhui China 230022
    3 The 307th Hospital of Chinese people's Liberation Army Beijing Beijing China 100021
    4 Beijing Cancer Hospital Beijing Beijing China 100036
    5 Sun Yat-sen University Cancer Center Guangzhou Guangdong China 510060
    6 Peking University Shenzhen Hospital Shenzhen Guangdong China 518036
    7 Cangzhou Central Hospital Cangzhou Hebei China 061001
    8 Tumor Hospital of Hebei Province Shijiazhuang Hebei China 050019
    9 Harbin Medical University Cancer Hospital Ha'erbin Heilongjiang China 150081
    10 Henan Cancer Hospital Zhengzhou Henan China 450008
    11 Hunan Cancer Hospital Changsha Hunan China
    12 Zhejiang Cancer Hospital Hangzhou Jiangsu China 310022
    13 Jiangsu Cancer Hospital Nanjing Jiangsu China 210009
    14 Jiangsu Province Hospital Nanjing Jiangsu China 210029
    15 The Third Hospital of Nanchang Nanchang Jiangxi China 330009
    16 Jilin Cancer Hospital Changchun Jilin China 130012
    17 The First Hospital of Jilin University Changchun Jilin China 130021
    18 Liaoning Cancer Hospital & Institute Shenyang Liaoning China 110042
    19 Jinan Central Hospital Jinan Shandong China 250013
    20 Fudan University Shanghai Cancer Center Shanghai Shanghai China 200032
    21 Fudan University ZhongShan Hospital Shanghai Shanghai China 200032
    22 Tianjin Medical University Cancer Institute and Hospital Tianjin Tianjin China 300060

    Sponsors and Collaborators

    • Chipscreen Biosciences, Ltd.

    Investigators

    • Principal Investigator: Zefei Jiang, 307 Hospital of PLA

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Chipscreen Biosciences, Ltd.
    ClinicalTrials.gov Identifier:
    NCT02482753
    Other Study ID Numbers:
    • CDM301
    First Posted:
    Jun 26, 2015
    Last Update Posted:
    Jan 12, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Chipscreen Biosciences, Ltd.
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jan 12, 2022