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

• ClinicalTrials.gov Identifier: NCT02482753
• Recruitment Status: Completed
• First Posted: June 26, 2015
• Last Update Posted: January 12, 2022
• Sponsor: Chipscreen Biosciences, Ltd.
• Information provided by (Responsible Party): Chipscreen Biosciences, Ltd.

Tracking Information

• First Submitted Date: June 17, 2015
• First Posted Date: June 26, 2015
• Last Update Posted Date: January 12, 2022
• Actual Study Start Date: July 2015
• Actual Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 23, 2015)

• progression-free survival (PFS), double-blinded period [ Time Frame: 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
• pharmacokinetic profiles of Chidamide, open-label period [ Time Frame: 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)
• pharmacokinetic profiles of exemestane, open-label period [ Time Frame: 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)
• acetylation level of histone H3, open-label period [ Time Frame: 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).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 23, 2015)

• overall survival, double-blinded period [ Time Frame: Time from randomization to death from any cause, assessed up to 6 years ]
  OS is measured from the date of randomization until death
• duration of response (DOR), double-blinded period [ Time Frame: 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
• objective response rate (ORR), open-label period and double-blinded period [ Time Frame: 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)
• clinical benefit rate (CBR), open-label period and double-blinded period [ Time Frame: 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)
• PFS, open-label period [ Time Frame: 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Trial of Chidamide in Combination With Exemestane in Patients With Advanced Breast Cancer
• Official Title: A Phase III Trial of Chidamide in Combination With Exemestane in Patients With Hormone Receptor-Positive Advanced Breast Cancer (ACE)
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Breast Cancer

Intervention

• Drug: Chidamide
  30 mg, administered orally twice per week (BIW)
  Other Name: CS055
• Drug: exemestane
  25 mg, PO daily
  Other Name: Aromasin
• Drug: placebo
  Administered orally twice per week (BIW)
  Other Name: Simulation tablet of Chidamide

Study Arms

• 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.
  Interventions:

  • Drug: Chidamide
  • Drug: exemestane
• 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.
  Interventions:

  • Drug: Chidamide
  • Drug: exemestane
• 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.
  Interventions:

  • Drug: exemestane
  • Drug: placebo

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 11, 2018): 365
• Original Estimated Enrollment (submitted: June 23, 2015): 348
• Actual Study Completion Date: February 2021
• Actual Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT02482753
• Other Study ID Numbers: CDM301
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Chipscreen Biosciences, Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Chipscreen Biosciences, Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Zefei Jiang; 307 Hospital of PLA

• PRS Account: Chipscreen Biosciences, Ltd.
• Verification Date: January 2022