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

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of trilaciclib combined with standard treatment project as a neoadjuvant treatment for triple negative breast cancer

Detailed Description
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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.

Official Title
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A Prospective, Randomized, Controlled Phase II Clinical Study of Trilaciclib Combined With Standard Treatment Project As a Neoadjuvant Treatment For Triple Negative Breast Cancer

Conditions
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Breast Neoplasm

Intervention / Treatment
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* Drug: Trilaciclib plus chemotherapy
* Drug: Chemotherapy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trilaciclib plus chemotherapy (Trilaciclib+AC-T)<br>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 | Drug: Trilaciclib plus chemotherapy<br>* 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<br>* Other names: Trilaciclib+AC-T;|
| Experimental: Chemotherapy (AC-T)<br>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 | Drug: Chemotherapy<br>* 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<br>* Other names: AC-T;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of CIN | The incidence of ≥3 grade neutropenia | From date of randomization until the date of surgery, assessed up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of CIT | The incidence of ≥3 grade thrombopenia | From date of randomization until the date of surgery, assessed up to 6 months | 
| The incidence of CIA | The incidence of ≥3 grade anemia | From date of randomization until the date of surgery, assessed up to 6 months | 
| pCR rate | Rate of pCR using the definition of ypT0/Tis ypN0 as assessed by the local pathologist. | From date of randomization until the date of surgery, assessed up to 6 months. | 
| ORR | Objective Response Rate | From date of randomization until the date of PD (up to 24 months) | 
| OS | Overall survival | From date of randomization until the date of death(up to 24 months) | 
| DFS | Disease-free survival | From date of randomization until the date of toxicity or PD (up to 24 months) | 
| Adverse event | Number of participants with adverse events as a measure of safety and tolerability | Frame:From date of randomization until the date of toxicity or PD (up to 24 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Trilaciclib/TNBC/Neoadjuvant