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Chidamide Plus PD-1 Plus Paclitaxel of Neoadjuvant Treatment in Low HR Expression,HER2-negative Early Breast Cancer.

Primary Purpose

Breast Cancer

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Chidamide Plus Toripalimab Plus Paclitaxel
Sponsored by
Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 1.18-75 years old. 2.ECOG whole-body status (performance status , PS) grade 0 to 1. 3.ER and PR IHC showed <10% staining and HER2 negative. 4.The patients who receive at least 2 neoadjuvant sessions with anthracycline are assessed to SD (4 anthracycline-containing sessions) or PD with breast MRI, CT or ultrasound according to the RECIST standard. 5.The patients refuse prior surgical treatment (the patient requires breast preservation, but it cannot be performed by surgical consultation), or it is not suitable for prior surgical treatment. 6.The main organ function is normal, that is, to meet the following criteria: the criteria for blood routine examination: ANC≥1.5×109/L; PLT≥100×109/L; Hb≥90g/L; the criteria for biochemical examination: TBIL<1.5×ULN; ALT and AST<2.5×ULN; BUN and Cr ≤ 1.5 × ULN or endogenous creatinine clearance rate ≥ 50ml/min (Cockcroft-Gault formula). 7.No malabsorption or other gastrointestinal disorders that affect drug absorption 8.Serum pregnancy tests for women of childbearing age must be negative within 7 days before treatment; all enrolled patients (whether male or female) should have adequate barrier contraception throughout the treatment period and within 4 weeks of treatment. 9.The subjects volunteer to join the study and sign informed consent, with good compliance and cooperated with follow-up. Exclusion Criteria: Previous use of investigational drugs such as PD-1 or PD-L1 mAb; sidabamine or other HDAC inhibitors, and taxane-based chemotherapies (including paclitaxel or docetaxel). Distant metastases, but enrollment could be considered if the distant metastatic lesion is confined to the ipsilateral cervical lymph exclusion criteria node only. Unstable systemic disease (including active infection, poorly controlled hypertension, unstable angina pectoris, congestive heart failure, hepatic, renal, or metabolic disease, etc). Any other malignancy within five years (except completely cured cervical carcinoma in situ or basal or squamous epithelial skin carcinoma). For known human immunodeficiency virus (HIV) infection, hepatitis B virus carriers must be treated for anti-hepatitis B virus replication during antitumor therapy. Prior history of clear neurological or psychiatric disorders, including epilepsy or dementia. Pregnant or lactating women. Any unstable or potentially jeopardizing patient safety and its compliance to the study. Other situations that investigators think it is unsuitable for enrollment.

Sites / Locations

  • Sun Yat-sen University Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Chidamide Plus Toripalimab Plus Paclitaxel

Arm Description

Cedaramine: 20mg, twice a week.Toripalimab: 240mg, once in 3 weeks,intravenous.Paclitaxel: 175mg / m2, once in 3 weeks, routine preventive anti-allergy treatment, surgery after 4 cycles of IV infusion.

Outcomes

Primary Outcome Measures

Pathology tpCR (ypT0/is, ypN0) rate
After completion of neoadjuvant therapy and surgery, there was no residual invasive carcinoma in the pathological evaluation of hematoxylin-and eosin-stained resected breast cancer samples and all ipsilateral lymph node samples. Count pCR rate in patients undergoing surgery.

Secondary Outcome Measures

Objective response rate (ORR)
The proportion of subjects who achieved CR or PR as optimal tumor response in the ITT population, as assessed by the efficacy evaluation criteria for solid tumors (RECIST1.1).
Disease-free survival (DFS)
Defined as the time interval from the first day of no disease (the date of surgery) to the first recording of a related event, including postoperative disease recurrence or metastasis and death from any cause.
Disease-free survival in 3 years
Defined as disease-free survival for all patients undergoing surgery from the first day of no disease ( the date of surgery) to 3 years.
Event-free survival (EFS)
Defined as the time interval from the first day of no disease (the date of surgery) to the first recording of related events, including postoperative disease recurrence or metastasis.

Full Information

First Posted
February 19, 2023
Last Updated
February 19, 2023
Sponsor
Sun Yat-sen University
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1. Study Identification

Unique Protocol Identification Number
NCT05749575
Brief Title
Chidamide Plus PD-1 Plus Paclitaxel of Neoadjuvant Treatment in Low HR Expression,HER2-negative Early Breast Cancer.
Official Title
A Prospective, Open-label, Phase II Clinical Trial of Chidamide, PD-1 Monoclonal Antibody and Paclitaxel in Neoadjuvant Therapy for Low Hormone Receptor(HR) Expression,HER2-negative Early Breast Cancer.
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 2023 (Anticipated)
Primary Completion Date
August 2023 (Anticipated)
Study Completion Date
August 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Triple-negative breast cancer has always been a difficult problem in clinical practice because of its young onset age, high aggressiveness, no clear therapeutic target and poor clinical prognosis. The treatment of triple-negative breast cancer is mainly chemotherapy, and in order to break the current dilemma, new treatments must be introduced. Immunotherapy is one of the most high-profile treatments. The KEYNOTE-522 study and Impassion 031 Study have found that immunotherapy can significantly improve the pCR of patients with triple yin breast cancer, rate, independent of PD-L1 expression status, and good safety.Cedardenamine is a histone deacetylation (HDAC) inhibitor developed in China.Many studies suggest that the use of sidabamine will likely enhance the efficacy of PD-1 / PD-L1 mAb in breast cancer and expand the use of PD-1 / PD-L1 mAb in the beneficiary population of breast cancer
Detailed Description
Cedaramine can effectively inhibit subtypes 1,2,3 of HDAC class I and type 10 of class IIb. Sidabamide can directly induce cycle arrest and apoptosis in tumors and has demonstrated its clinical role in lymphoma and breast cancer.besides, In recent years, many studies have found that HDAC inhibitors also have their functions in regulating immunity, Such as: 1) upregulated tumor antigen / co-stimulatory molecule / receptor levels of tumor cells (such as MHC I / II, PRAME, MIC A/B, PDL-1, etc.), Make it easier to be recognized by the immune system; 2) Initialize the natural immune system, Activating NK cell activity; 3) Initialize the acquired immune system, Activating initial T cells (Naive T cells) to target tumor antigen; 4) Increase the CD8 + effector cells that kill tumor cells, Downregulation of the immunosuppressive cells, Such as the Treg 6 7 and MDSC, Promote the formation and maintenance of acquired immune memory T cells. Preclinical studies suggested that HDAC was synergistic with PD-1 / PD-L1 antibodies and could serve as a sensitizer for PD-1 / PD-L1 antibodies. A phase I study in solid tumors found that sitabenamine combined with natureumab had an objective response rate (ORR) of 48% and a disease control rate (DCR) of 87%.Therefore, we conduct this study to observe the efficacy and safety of neoadjuvant therapy in early HR low-expression ,HER2-negative breast cancer patients treated with PD-1 mAb and paclitaxel.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Chidamide Plus Toripalimab Plus Paclitaxel
Arm Type
Experimental
Arm Description
Cedaramine: 20mg, twice a week.Toripalimab: 240mg, once in 3 weeks,intravenous.Paclitaxel: 175mg / m2, once in 3 weeks, routine preventive anti-allergy treatment, surgery after 4 cycles of IV infusion.
Intervention Type
Drug
Intervention Name(s)
Chidamide Plus Toripalimab Plus Paclitaxel
Intervention Description
Each participant receives chidamide plus toripalimab plus paclitaxel
Primary Outcome Measure Information:
Title
Pathology tpCR (ypT0/is, ypN0) rate
Description
After completion of neoadjuvant therapy and surgery, there was no residual invasive carcinoma in the pathological evaluation of hematoxylin-and eosin-stained resected breast cancer samples and all ipsilateral lymph node samples. Count pCR rate in patients undergoing surgery.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
The proportion of subjects who achieved CR or PR as optimal tumor response in the ITT population, as assessed by the efficacy evaluation criteria for solid tumors (RECIST1.1).
Time Frame
1 year
Title
Disease-free survival (DFS)
Description
Defined as the time interval from the first day of no disease (the date of surgery) to the first recording of a related event, including postoperative disease recurrence or metastasis and death from any cause.
Time Frame
1 year
Title
Disease-free survival in 3 years
Description
Defined as disease-free survival for all patients undergoing surgery from the first day of no disease ( the date of surgery) to 3 years.
Time Frame
3 year
Title
Event-free survival (EFS)
Description
Defined as the time interval from the first day of no disease (the date of surgery) to the first recording of related events, including postoperative disease recurrence or metastasis.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 1.18-75 years old. 2.ECOG whole-body status (performance status , PS) grade 0 to 1. 3.ER and PR IHC showed <10% staining and HER2 negative. 4.The patients who receive at least 2 neoadjuvant sessions with anthracycline are assessed to SD (4 anthracycline-containing sessions) or PD with breast MRI, CT or ultrasound according to the RECIST standard. 5.The patients refuse prior surgical treatment (the patient requires breast preservation, but it cannot be performed by surgical consultation), or it is not suitable for prior surgical treatment. 6.The main organ function is normal, that is, to meet the following criteria: the criteria for blood routine examination: ANC≥1.5×109/L; PLT≥100×109/L; Hb≥90g/L; the criteria for biochemical examination: TBIL<1.5×ULN; ALT and AST<2.5×ULN; BUN and Cr ≤ 1.5 × ULN or endogenous creatinine clearance rate ≥ 50ml/min (Cockcroft-Gault formula). 7.No malabsorption or other gastrointestinal disorders that affect drug absorption 8.Serum pregnancy tests for women of childbearing age must be negative within 7 days before treatment; all enrolled patients (whether male or female) should have adequate barrier contraception throughout the treatment period and within 4 weeks of treatment. 9.The subjects volunteer to join the study and sign informed consent, with good compliance and cooperated with follow-up. Exclusion Criteria: Previous use of investigational drugs such as PD-1 or PD-L1 mAb; sidabamine or other HDAC inhibitors, and taxane-based chemotherapies (including paclitaxel or docetaxel). Distant metastases, but enrollment could be considered if the distant metastatic lesion is confined to the ipsilateral cervical lymph exclusion criteria node only. Unstable systemic disease (including active infection, poorly controlled hypertension, unstable angina pectoris, congestive heart failure, hepatic, renal, or metabolic disease, etc). Any other malignancy within five years (except completely cured cervical carcinoma in situ or basal or squamous epithelial skin carcinoma). For known human immunodeficiency virus (HIV) infection, hepatitis B virus carriers must be treated for anti-hepatitis B virus replication during antitumor therapy. Prior history of clear neurological or psychiatric disorders, including epilepsy or dementia. Pregnant or lactating women. Any unstable or potentially jeopardizing patient safety and its compliance to the study. Other situations that investigators think it is unsuitable for enrollment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Fei Xu, MD
Phone
+86-13711277870
Email
xufei@sysucc.org.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Kuikui Jiang, MD
Phone
+86-15210589011
Email
jiangkk@sysucc.org.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fei Xu, MD
Organizational Affiliation
Sun Yat-sen University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sun Yat-sen University Cancer Center
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fei Xu, MD
Phone
+86-13711277870
Email
xufei@sysucc.org.cn
First Name & Middle Initial & Last Name & Degree
Fei Xu, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Chidamide Plus PD-1 Plus Paclitaxel of Neoadjuvant Treatment in Low HR Expression,HER2-negative Early Breast Cancer.

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