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The Study of Trilaciclib Combined With Chemotherapy On The Neoadjuvant Therapy of TNBC

Primary Purpose

Breast Neoplasm

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Trilaciclib plus chemotherapy
Chemotherapy
Sponsored by
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Neoplasm focused on measuring Trilaciclib/TNBC/Neoadjuvant

Eligibility Criteria

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

Inclusion Criteria: Newly treated patients aged ≥ 18 years; ECOG score 0-1; Breast cancer meets the following standards: Histologically confirmed invasive breast cancer Tumor staging: cT2-4, cNany, cM0 or cT1, cN1-3, cM0; Hormone (estrogen and progesterone) receptor negative tumors confirmed by histological or cytological records (defined as nuclear staining rate<1% based on immunohistochemistry [IHC] evaluation) and Her-2 negative, non overexpressing tumors (based on IHC [0 or 1+] or in situ hybridization [ratio<2.0] or average Her-2 gene copy number<4 signals/nucleus); Within the first two weeks of the screening period, no G-CSF, TPO, IL-11, ESA, iron, platelet transfusion, or blood transfusion have been used. The functional level of the main organs must meet the following requirements: Blood routine: Neutrophils (ANC)≥1.5×109/L, platelet count (PLT)≥90×109/L, hemoglobin (Hb)≥90g/L Blood biochemistry: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN, serum creatinine (Cr)≤1.5×ULN, bilirubin<1.5 ULN; For female patients who have not undergone menopause or surgical sterilization: During the treatment period and at least 7 months after the last dose in the study treatment, consent to abstinence or use effective contraceptive methods. Volunteer join this study, sign an informed consent form, have good compliance, and are willing to cooperate with follow-up. Exclusion Criteria: Previously received anti-tumor treatment for any malignant tumor; Subjects who are unable to accept or tolerate preoperative chemotherapy due to various reasons; The patient has undergone major surgical procedures unrelated to breast cancer within 4 weeks before enrollment, or has not fully recovered from such surgical procedures; Serious heart disease or discomfort, including but not limited to the following diseases: A confirmed history of heart failure or systolic dysfunction (LVEF<50%); High risk uncontrolled arrhythmias, such as atrial tachycardia, resting heart rate>100bpm, significant ventricular arrhythmias (such as ventricular tachycardia) or higher-level atrioventricular block (such as Mobitz II second degree atrioventricular block or third degree atrioventricular block); Angina pectoris requiring treatment with anti angina drugs; Heart valve disease with clinical significance; ECG shows transmural myocardial infarction; Poor control of hypertension (systolic blood pressure>180mmHg and/or diastolic blood pressure>100mmHg) Those with a known history of allergies to the drug components of this protocol; Breastfeeding female patients, those with fertility and positive baseline pregnancy test results, or those of childbearing age who are unwilling to take effective contraceptive measures during the entire trial period and within 7 months after the last study medication; Any other circumstances in which the researcher believes that the patient is not suitable to participate in this study.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Trilaciclib plus chemotherapy (Trilaciclib+AC-T)

    Chemotherapy (AC-T)

    Arm Description

    Trilaciclib: 240mg/m2 IV d1,within 4h before chemotherapy epirubicin: 100mg/m2 IV d1,Q2W/Q3W (decided by researchers),4 cycles cyclophosphamide:600mg/m2 IV d1,Q2W/Q3W (decided by researchers),4 cycles albumin-bound paclitaxel:100mg/m2 IV d1,8,15,Q3W,4cycles

    epirubicin: 100mg/m2 IV d1,Q2W/Q3W (decided by researchers),4 cycles cyclophosphamide:600mg/m2 IV d1,Q2W/Q3W (decided by researchers),4 cycles albumin-bound paclitaxel:100mg/m2 IV d1,8,15,Q3W,4cycles

    Outcomes

    Primary Outcome Measures

    The incidence of CIN
    The incidence of ≥3 grade neutropenia

    Secondary Outcome Measures

    The incidence of CIT
    The incidence of ≥3 grade thrombopenia
    The incidence of CIA
    The incidence of ≥3 grade anemia
    pCR rate
    Rate of pCR using the definition of ypT0/Tis ypN0 as assessed by the local pathologist.
    ORR
    Objective Response Rate
    OS
    Overall survival
    DFS
    Disease-free survival
    Adverse event
    Number of participants with adverse events as a measure of safety and tolerability

    Full Information

    First Posted
    May 8, 2023
    Last Updated
    July 21, 2023
    Sponsor
    Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05862610
    Brief Title
    The Study of Trilaciclib Combined With Chemotherapy On The Neoadjuvant Therapy of TNBC
    Official Title
    A Prospective, Randomized, Controlled Phase II Clinical Study of Trilaciclib Combined With Standard Treatment Project As a Neoadjuvant Treatment For Triple Negative Breast Cancer
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    July 30, 2023 (Anticipated)
    Primary Completion Date
    December 30, 2026 (Anticipated)
    Study Completion Date
    June 30, 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Sun Yat-Sen Memorial Hospital of 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
    To evaluate the efficacy and safety of trilaciclib combined with standard treatment project as a neoadjuvant treatment for triple negative breast cancer
    Detailed Description
    Trilaciclib indication: Trilaciclib, a CDK4/6 inhibitor, was used before chemotherapy to reduce the incidence of bone marrow suppression and approved by the FDA for small cell lung cancer patients in 2021.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Breast Neoplasm
    Keywords
    Trilaciclib/TNBC/Neoadjuvant

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    150 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Trilaciclib plus chemotherapy (Trilaciclib+AC-T)
    Arm Type
    Experimental
    Arm Description
    Trilaciclib: 240mg/m2 IV d1,within 4h before chemotherapy epirubicin: 100mg/m2 IV d1,Q2W/Q3W (decided by researchers),4 cycles cyclophosphamide:600mg/m2 IV d1,Q2W/Q3W (decided by researchers),4 cycles albumin-bound paclitaxel:100mg/m2 IV d1,8,15,Q3W,4cycles
    Arm Title
    Chemotherapy (AC-T)
    Arm Type
    Experimental
    Arm Description
    epirubicin: 100mg/m2 IV d1,Q2W/Q3W (decided by researchers),4 cycles cyclophosphamide:600mg/m2 IV d1,Q2W/Q3W (decided by researchers),4 cycles albumin-bound paclitaxel:100mg/m2 IV d1,8,15,Q3W,4cycles
    Intervention Type
    Drug
    Intervention Name(s)
    Trilaciclib plus chemotherapy
    Other Intervention Name(s)
    Trilaciclib+AC-T
    Intervention Description
    Trilaciclib: 240mg/m2 IV d1,within 4h before chemotherapy epirubicin: 100mg/m2 IV d1,Q2W/Q3W (decided by researchers),4 cycles cyclophosphamide:600mg/m2 IV d1,Q2W/Q3W (decided by researchers),4 cycles albumin-bound paclitaxel:100mg/m2 IV d1,8,15,Q3W,4cycles
    Intervention Type
    Drug
    Intervention Name(s)
    Chemotherapy
    Other Intervention Name(s)
    AC-T
    Intervention Description
    epirubicin: 100mg/m2 IV d1,Q2W/Q3W (decided by researchers),4 cycles cyclophosphamide:600mg/m2 IV d1,Q2W/Q3W (decided by researchers),4 cycles albumin-bound paclitaxel:100mg/m2 IV d1,8,15,Q3W,4cycles
    Primary Outcome Measure Information:
    Title
    The incidence of CIN
    Description
    The incidence of ≥3 grade neutropenia
    Time Frame
    From date of randomization until the date of surgery, assessed up to 6 months
    Secondary Outcome Measure Information:
    Title
    The incidence of CIT
    Description
    The incidence of ≥3 grade thrombopenia
    Time Frame
    From date of randomization until the date of surgery, assessed up to 6 months
    Title
    The incidence of CIA
    Description
    The incidence of ≥3 grade anemia
    Time Frame
    From date of randomization until the date of surgery, assessed up to 6 months
    Title
    pCR rate
    Description
    Rate of pCR using the definition of ypT0/Tis ypN0 as assessed by the local pathologist.
    Time Frame
    From date of randomization until the date of surgery, assessed up to 6 months.
    Title
    ORR
    Description
    Objective Response Rate
    Time Frame
    From date of randomization until the date of PD (up to 24 months)
    Title
    OS
    Description
    Overall survival
    Time Frame
    From date of randomization until the date of death(up to 24 months)
    Title
    DFS
    Description
    Disease-free survival
    Time Frame
    From date of randomization until the date of toxicity or PD (up to 24 months)
    Title
    Adverse event
    Description
    Number of participants with adverse events as a measure of safety and tolerability
    Time Frame
    Frame:From date of randomization until the date of toxicity or PD (up to 24 months)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Newly treated patients aged ≥ 18 years; ECOG score 0-1; Breast cancer meets the following standards: Histologically confirmed invasive breast cancer Tumor staging: cT2-4, cNany, cM0 or cT1, cN1-3, cM0; Hormone (estrogen and progesterone) receptor negative tumors confirmed by histological or cytological records (defined as nuclear staining rate<1% based on immunohistochemistry [IHC] evaluation) and Her-2 negative, non overexpressing tumors (based on IHC [0 or 1+] or in situ hybridization [ratio<2.0] or average Her-2 gene copy number<4 signals/nucleus); Within the first two weeks of the screening period, no G-CSF, TPO, IL-11, ESA, iron, platelet transfusion, or blood transfusion have been used. The functional level of the main organs must meet the following requirements: Blood routine: Neutrophils (ANC)≥1.5×109/L, platelet count (PLT)≥90×109/L, hemoglobin (Hb)≥90g/L Blood biochemistry: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN, serum creatinine (Cr)≤1.5×ULN, bilirubin<1.5 ULN; For female patients who have not undergone menopause or surgical sterilization: During the treatment period and at least 7 months after the last dose in the study treatment, consent to abstinence or use effective contraceptive methods. Volunteer join this study, sign an informed consent form, have good compliance, and are willing to cooperate with follow-up. Exclusion Criteria: Previously received anti-tumor treatment for any malignant tumor; Subjects who are unable to accept or tolerate preoperative chemotherapy due to various reasons; The patient has undergone major surgical procedures unrelated to breast cancer within 4 weeks before enrollment, or has not fully recovered from such surgical procedures; Serious heart disease or discomfort, including but not limited to the following diseases: A confirmed history of heart failure or systolic dysfunction (LVEF<50%); High risk uncontrolled arrhythmias, such as atrial tachycardia, resting heart rate>100bpm, significant ventricular arrhythmias (such as ventricular tachycardia) or higher-level atrioventricular block (such as Mobitz II second degree atrioventricular block or third degree atrioventricular block); Angina pectoris requiring treatment with anti angina drugs; Heart valve disease with clinical significance; ECG shows transmural myocardial infarction; Poor control of hypertension (systolic blood pressure>180mmHg and/or diastolic blood pressure>100mmHg) Those with a known history of allergies to the drug components of this protocol; Breastfeeding female patients, those with fertility and positive baseline pregnancy test results, or those of childbearing age who are unwilling to take effective contraceptive measures during the entire trial period and within 7 months after the last study medication; Any other circumstances in which the researcher believes that the patient is not suitable to participate in this study.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Qiang Liu, Doc
    Phone
    020-81332199
    Email
    victorlq@hotmail.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Yudong Li, Doc
    Phone
    020-81332199
    Email
    nihao_0105@163.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Qiang Liu, Doc
    Organizational Affiliation
    Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    31504118
    Citation
    Weiss JM, Csoszi T, Maglakelidze M, Hoyer RJ, Beck JT, Domine Gomez M, Lowczak A, Aljumaily R, Rocha Lima CM, Boccia RV, Hanna W, Nikolinakos P, Chiu VK, Owonikoko TK, Schuster SR, Hussein MA, Richards DA, Sawrycki P, Bulat I, Hamm JT, Hart LL, Adler S, Antal JM, Lai AY, Sorrentino JA, Yang Z, Malik RK, Morris SR, Roberts PJ, Dragnev KH; G1T28-02 Study Group. Myelopreservation with the CDK4/6 inhibitor trilaciclib in patients with small-cell lung cancer receiving first-line chemotherapy: a phase Ib/randomized phase II trial. Ann Oncol. 2019 Oct 1;30(10):1613-1621. doi: 10.1093/annonc/mdz278.
    Results Reference
    background
    PubMed Identifier
    33348420
    Citation
    Daniel D, Kuchava V, Bondarenko I, Ivashchuk O, Reddy S, Jaal J, Kudaba I, Hart L, Matitashvili A, Pritchett Y, Morris SR, Sorrentino JA, Antal JM, Goldschmidt J. Trilaciclib prior to chemotherapy and atezolizumab in patients with newly diagnosed extensive-stage small cell lung cancer: A multicentre, randomised, double-blind, placebo-controlled Phase II trial. Int J Cancer. 2020 Dec 21;148(10):2557-70. doi: 10.1002/ijc.33453. Online ahead of print.
    Results Reference
    background
    PubMed Identifier
    33123968
    Citation
    Hart LL, Ferrarotto R, Andric ZG, Beck JT, Subramanian J, Radosavljevic DZ, Zaric B, Hanna WT, Aljumaily R, Owonikoko TK, Verhoeven D, Xiao J, Morris SR, Antal JM, Hussein MA. Myelopreservation with Trilaciclib in Patients Receiving Topotecan for Small Cell Lung Cancer: Results from a Randomized, Double-Blind, Placebo-Controlled Phase II Study. Adv Ther. 2021 Jan;38(1):350-365. doi: 10.1007/s12325-020-01538-0. Epub 2020 Oct 29.
    Results Reference
    background
    PubMed Identifier
    33895103
    Citation
    Weiss J, Goldschmidt J, Andric Z, Dragnev KH, Gwaltney C, Skaltsa K, Pritchett Y, Antal JM, Morris SR, Daniel D. Effects of Trilaciclib on Chemotherapy-Induced Myelosuppression and Patient-Reported Outcomes in Patients with Extensive-Stage Small Cell Lung Cancer: Pooled Results from Three Phase II Randomized, Double-Blind, Placebo-Controlled Studies. Clin Lung Cancer. 2021 Sep;22(5):449-460. doi: 10.1016/j.cllc.2021.03.010. Epub 2021 Mar 26.
    Results Reference
    background
    PubMed Identifier
    33004541
    Citation
    Lai AY, Sorrentino JA, Dragnev KH, Weiss JM, Owonikoko TK, Rytlewski JA, Hood J, Yang Z, Malik RK, Strum JC, Roberts PJ. CDK4/6 inhibition enhances antitumor efficacy of chemotherapy and immune checkpoint inhibitor combinations in preclinical models and enhances T-cell activation in patients with SCLC receiving chemotherapy. J Immunother Cancer. 2020 Oct;8(2):e000847. doi: 10.1136/jitc-2020-000847.
    Results Reference
    background

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    The Study of Trilaciclib Combined With Chemotherapy On The Neoadjuvant Therapy of TNBC

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