trilaciclib in patients with early-stage hr-negative breast cancer receiving adjuvant chemotherapy

Conditions: Breast Neoplasms

Summary: the goal of this multicenter, two-cohort, exploratory clinical trial is to evaluate patients with early stage hormone receptor-negative breast cancer receiving standard adjuvant chemotherapy after surgery. the main question it aims to answer is: • the efficacy and safety of trilaciclib administered before standard adjuvant chemotherapy regimen using the incidence of grade 3/4 neutropenia as the primary efficacy endpoint. participants will divide into two treatment cohorts according to molecular typing type: * cohort a will be planned to include post-operative triple-negative breast cancer(tnbc) patients with lymph node positive or tumor \> 2 cm treated with trilaciclib combined with epirubicin and cyclophosphamide followed by weekly paclitaxel; * cohort b will be planned to include her2-positive/hr-negative breast cancer patients with axillary node positive or tumor \> 2 cm treated with trilaciclib combined with docetaxel, carboplatin and trastuzumab with or without pertuzumab.


Eligibility criteria:
inclusion criteria: * age ≥ 18 years; * breast cancer meets the following criteria: * histologically or cytologically confirmed and adequately resected non-metastatic primary invasive breast cancer; * cohort a only: er, pr negative (\< 1% nuclear staining as assessed by immunohistochemistry \[ihc\]), her2 negative (her2/cep17 ratio \< 2.0 or mean her2 gene copy number \< 4 signals/nucleus detected by ihc 0 or 1 + or in situ hybridization \[ish\]); patients with concurrent bilateral invasive disease met the inclusion criteria if both lesions were hr negative/her2 negative. * cohort b only: er, pr negative (\< 1% nuclear staining as assessed by immunohistochemistry \[ihc\]); her2 positive: her2/cep17 ratio ≥ 2.0 or her2 gene copy number ≥ 4 signals/nucleus detected by ihc 3 + and ish; her2 gene copy number ≥ 6 signals/nucleus detected by ihc 3 + or 2 + and ish); patients with concurrent bilateral invasive disease met the inclusion criteria if both lesions were hr negative/her2 positive. * subjects must have positive lymph nodes or tumors \> 2 cm; * the interval between radical surgery and the first dose ≤ 60 days; * eastern cooperative oncology group (ecog) performance score 0-1; * have appropriate organ function, meet the following criteria: (1) have appropriate bone marrow function: hb ≥ 100 g/l (no esa and blood transfusion within 14 days before the first dose); absolute neutrophil count (anc) ≥ 2 × 10\^9/l (no g-csf within 14 days before the first dose); platelet count ≥ 100 × 10\^9/l (no rhtpo/rhil-11 and platelet transfusion within 14 days before the first dose); (2) appropriate liver and kidney function: alanine aminotransferase (alt) ≤ 2.5 × upper limit of normal (uln), aspartate aminotransferase (ast) ≤ 2.5 × uln, total bilirubin (tbil) ≤ 1.5 × uln, serum creatinine ≤ 1.5 × uln, endogenous creatinine clearance \> 50 ml/min (cockcroft-gault formula); (3) appropriate cardiac function: left ventricular ejection fraction (lvef) ≥ 55%; * non-hematologic toxicities from prior surgical procedures recovered to ≤ grade 1 or baseline (except alopecia); * females of childbearing potential agree to practice reliable contraception during the clinical trial and have a negative serum or urine pregnancy test within 7 days prior to dosing; * voluntarily join this study and sign informed consent, have good compliance and are willing to cooperate with follow-up. exclusion criteria: * prior neoadjuvant therapy (including chemotherapy, targeted therapy, immunotherapy, or radiotherapy); * history of other malignancy within 5 years prior to first dose, except basal cell carcinoma and cervical carcinoma in situ; * any t4 or n2 or known n3 or m1 breast cancer; * subjects who cannot receive or tolerate postoperative chemotherapy for various reasons; * heart disease ineligible for epirubicin, docetaxel, trastuzumab/pertuzumab: * any documented history of myocardial infarction, congestive heart failure * angina pectoris requiring antianginal medication * grade 3 or 4 cardiac arrhythmia (nci ctcaev5.0) * clinically significant valvular heart disease; * poorly controlled hypertension (systolic blood pressure \> 180 mmhg and/or diastolic blood pressure \> 100 mmhg) * known history of hypersensitivity to the drug components of this protocol; * any other condition that, in the opinion of the investigator, would make the patient inappropriate for participation in this study.

Keywords: trilaciclib; hr-negative breast cancer; adjuvant therapy