Clinical Study of Chidamide Combined With Chemotherapy in Neoadjuvant Treatment of HR+/ HER2-BC

A Multicenter, Single-arm Prospective Phase II Study of Chidamide in Combination With Chemotherapy for Neoadjuvant Treatment of HR-positive/HER2-negative Breast Cancer

Neoadjuvant therapy for HR+/HER2- breast cancer is dominated by anthracycline combined with paclitaxel chemotherapy. Aggressive neoadjuvant chemotherapy can only achieve pCR in about 10% of PATIENTS with HR-positive breast cancer. The emergence of new targeted drugs brings new life and hope to HR-positive breast cancer patients.Basic studies have shown that the abnormal state of epigenetics is associated with the metastasis of drug resistance and recurrence of tumor histone deacetylase (HDAC) is an important regulator of epigenetic regulation, and drugs targeting HDAC provide a new strategy for tumor therapy. The ACE study suggests that selective HDAC inhibitor chidamide in combination with endocrine therapy significantly improves survival benefit in patients with hr-positive HER2-negative advanced breast cancer who relapsed or progressed after endocrine therapy, providing a new treatment option for these patients.In conclusion, we hypothesize that neoadjuvant therapy with chidamide combination therapy provides a better strategy for patients with HR + /HER2 - breast adenocarcinoma.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Combination product: Chidamide

Detailed Description

A total of 59 patients with stage Ii-III HR + / HER2 - breast cancer were enrolled in a multi-center, single-arm prospective design. The main purpose of the study was to observe the efficacy and safety of chidamide combined with chemotherapy in neoadjuvant treatment of stage II-III HR + / HER2 - breast cancer Breast MRI and other imaging examinations were reviewed every 2 cycles to evaluate the efficacy. If the efficacy was accurate, surgical treatment was performed within 4 weeks after the 8th cycle of neoadjuvant therapy. If the efficacy was SD+/PD, the study would be withdrawn Within 4 weeks after surgical treatment, the resected tumor tissue and lymph nodes were histopathologically examined (including the pathology of the tumor resection margin). The pathological sections were uniformly lent to the master research unit for unified review

• Study Type: Interventional
• Enrollment (Anticipated): 59
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Caigang Liu, doctoral; Phone Number: 18940264967; Email: liucg@sj-hospital.org

Study Locations

• China
  • Heilongjiang
    • Haerbin, Heilongjiang, China
      • Recruiting
      • Cancer Hospital Affiliated to Harbin Medical University
      • Contact: Zhigao Li, professor
  • Jilin
    • Changchun, Jilin, China
      • Recruiting
      • Bethune First Hospital Of Jilin University
      • Contact: Dong Song, professor
  • Liaoning
    • Benxi, Liaoning, China
      • Recruiting
      • Health Science and Technology Information Center of Liaoning Health Industry Group Co., LTD
      • Contact: Honglu Li, professor
    • Dalian, Liaoning, China
      • Recruiting
      • Affiliated Zhongshan Hospital Dalian University
      • Contact: Dianlong Zhang, professor
    • Shenyang, Liaoning, China, 110004
      • Recruiting
      • Shengjing Hospital of China Medical University
      • Contact: Cai-Gang Liu, PHD; Phone Number: +86 18940254967; Email: liucg@sj-hospital.org
      • Principal Investigator: Cai-Gang Liu, PHD
    • Shenyang, Liaoning, China
      • Recruiting
      • The First Affiliated Hospital of China Medical University
      • Contact: Xinyu Zheng, professor
    • Shenyang, Liaoning, China
      • Recruiting
      • Liaoning Cancer Hospital
      • Contact: Hong Xu, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Women aged 18 years or older and 75 years or younger;
2. All patients were histopathologically confirmed to be estrogen receptor (ER) positive (& GT; 10%),HER2 receptor negative follows the 2018 ASCO-CAP HER2 negative interpretation guideline criteria;
3. Newly treated patients with stage II-III tumor staging meeting AJCC Version 8 criteria;
4. KPS score ≥70;

5. The functional level of the organ must meet the following requirements:

   • Bone marrow function
   • ANC ≥ 1.5×10 9 /L (growth factor not used within 14 days);
   • PLT ≥ 100×10 9 /L (no corrective treatment within 7 days);
   • Hb ≥ 100 g/L (no corrective treatment within 7 days);
   • Liver and kidney function
   • TBIL ≤1.5 x ULN;
   • ALT and AST≤3×ULN;
   • BUN and Cr≤1.5×ULN and creatinine clearance ≥50 mL/min (Cockcroft-Gault formula);
6. Able to undergo needle biopsy;
7. Volunteered to participate in the study, signed informed consent, had good compliance and was willing to cooperate with follow-up.

Exclusion Criteria:

-

Participants are not allowed to participate in the clinical study under any of the following conditions:

1. Have received any other form of anti-tumor therapy (chemotherapy, radiotherapy, molecular targeted therapy, endocrine therapy, etc.);
2. Receiving any other antitumor therapy;
3. Bilateral breast cancer, inflammatory breast cancer or ocessive breast cancer;
4. Stage IV breast cancer;
5. Breast cancer without histopathological diagnosis;
6. Other malignant tumors within the past 5 years, except cured carcinoma in situ of the cervix;
7. Severe heart, liver, kidney and other important organ dysfunction;
8. Inability to swallow, chronic diarrhea and intestinal obstruction, there are many factors affecting drug taking and absorption;
9. Participated in clinical trials of other drugs within 4 weeks before enrollment;
10. Known history of allergy to the drug components of this regimen; History of immunodeficiency, including HIV positive, HCV, live active hepatitis B or other acquired or congenital immune deficiency diseases, or a history of organ transplantation;
11. History of any heart disease, including :(1) medically required or clinically significant arrhythmia; (2) myocardium infarction; (3) heart failure; (4) Any other heart disease deemed unsuitable for the study by the investigator;
12. Pregnant, lactating women, fertile women with positive baseline pregnancy test or in the entire women of reproductive age who were unwilling to use effective contraception during the trial;
13. According to the investigator's judgment, there are comorbidities (including but) that seriously endanger the patient's safety or affect the patient's ability to complete the study not limited to severe hypertension, severe diabetes, active infection, etc., which cannot be controlled by drugs);
14. A clear past history of neurological or psychiatric disorders, including epilepsy or dementia. The investigator considered the patient unsuitable for the study in any other case.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: treatment group; Chidamide combined with EC -- T regimen was treated with 1 cycle every 21 days, followed by 4 cycles of EC followed by 4 cycles of T, a total of 8 cycles

Combination product: Chidamide; Chidamide: take orally twice a week,4 tablets/time (20mg/ time), the interval between two doses should not be less than 3 days (such as Monday and Thursday, Tuesday and Friday, Wednesday and Saturday, etc.), the day before chemotherapy, 30 minutes after breakfast； Chidamide: 20mg, orally, twice a week, oral for two weeks and one week, a total of 8 cycles； Epirubicin 90mg/m2 , ivgtt, d1 Cyclophosphamide 600mg/m 2, ivgtt, d1 Q3w, 4 cycle； sequential Docetaxel 100 mg/m 2, IVGtt, D1 Q3w, 4 cycle。; Other Names: Cyclophosphamide; Docetaxel; pharmorubicin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RCB 0-1 points ratio	Residual tumor burden	One month after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR（ypT0/is、ypN0）	There was no residual tumor	One month after surgery
bpCR（ypT0/is）	Breast pCRwith ypT0/is carcinoma in situ	One month after surgery
ORR	Proportion of patients who had a 30% reduction in tumor volume and maintained it for more than four weeks	Period of neoadjuvant therapy (treatment 1-6 months)
Breast retention rate	Percentage of patients with successful breast preservation	One month after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AE) and Serious Adverse Events (SAE)	Any adverse events	Period of neoadjuvant therapy (treatment 1-6 months)And chidamide 3 weeks after withdrawal

Collaborators and Investigators

• Sponsor: Shengjing Hospital
• Investigators: Principal Investigator: Caigang Liu, doctoral, Shengjing Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2022
• Primary Completion (Anticipated): May 23, 2023
• Study Completion (Anticipated): May 23, 2024

Study Registration Dates

• First Submitted: May 27, 2022
• First Submitted That Met QC Criteria: May 27, 2022
• First Posted (Actual): June 2, 2022

Study Record Updates

• Last Update Posted (Actual): June 6, 2022
• Last Update Submitted That Met QC Criteria: June 1, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Docetaxel; Cyclophosphamide; Epirubicin
• Other Study ID Numbers: CSIIT-C25

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No