Breast Neoplasms
Conditions
Keywords
Trilaciclib; HR-Negative Breast Cancer; Adjuvant Therapy
Brief 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.
Interventions
DRUGTrilaciclib
240 mg/m2, intravenous drip over 30 min within 4 hours before chemotherapy administration on the same day
DRUGEpirubicin
90 mg/m2, intravenous drip, d1, Q3W, 4 cycles.
DRUGCyclophosphamide
600 mg/m2, intravenous drip, d1, Q3W, 4 cycles.
DRUGPaclitaxel
80 mg/m2, intravenous drip, d1,8,15, Q3W, 4 cycles.
DRUGDocetaxel
75 mg/m2, intravenous drip, d1, Q3W, 6 cycles.
DRUGCarboplatin
area under curve(AUC) = 6, intravenous drip, d1, Q3W, 6 cycles.
DRUGTrastuzumab
8 mg/kg in Cycle 1, 6 mg/kg in subsequent cycles, intravenous drip, d1, Q3W, for 1 year.
DRUGPertuzumab
840mg in Cycle 1, 420mg in subsequent cycles, intravenous drip, d1, Q3W, for 1 year.
Sponsors
wang shusen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Grade 3/4 neutropenia | Up to 24 weeks | Proportion of subjects with at least one absolute neutrophil count (ANC) \< 1.0 × 10\^9/L enrolled and treated with at least one dose of trilaciclib |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neutrophil-related myeloprotective effects | Up to 24 weeks | Occurrence of febrile neutropenia adverse events(AEs) , and occurrence of Granulocyte colony-stimulating factor(G-CSF) administration |
| Red blood cell(RBC) -related myeloprotective effects | Up to 24 weeks | Occurrence of Grade 3/4 decrease of hemoglobin, occurrence and number of RBC transfusions on/after Week 5, and occurrence of erythropoiesis-stimulating agent(ESA) administration |
| Platelet-related myeloprotective effects | Up to 24 weeks | Occurrence of Grade 3/4 decrease of platelets, occurrence and number of platelet transfusions, and occurrence of rhTPO/Recombinant human interleukin-11(rhIL-11) administration |
| Myeloprotective Effects | Up to 24 months | Hospitalization due to chemotherapy-induced myelosuppression, dose reductions and delays, relative dose intensity(RDI) of chemotherapeutic agents |
| Safety and tolerability | Up to 24 months | Incidence of Treatment-Emergent Adverse Events as per CTCAE version 5.0 |
Countries
China
Contacts
Primary ContactShusen Wang, MD
Outcome results
None listed