Trilaciclib in Patients With Early-Stage HR-negative Breast Cancer Receiving Adjuvant Chemotherapy

Official title

A Prospective, Multi-cohort, Exploratory Phase II Study of Trilaciclib Combined With Standard Chemotherapy in The Adjuvant Treatment of Hormone Receptor (HR) Negative Breast Cancer

Overview

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

• Drug Trilaciclib
  240 mg/m2, intravenous drip over 30 min within 4 hours before chemotherapy administration on the same day
• Drug Epirubicin
  90 mg/m2, intravenous drip, d1, Q3W, 4 cycles.
• Drug Cyclophosphamide
  600 mg/m2, intravenous drip, d1, Q3W, 4 cycles.
• Drug Paclitaxel
  80 mg/m2, intravenous drip, d1,8,15, Q3W, 4 cycles.
• Drug Docetaxel
  75 mg/m2, intravenous drip, d1, Q3W, 6 cycles.
• Drug Carboplatin
  area under curve(AUC) = 6, intravenous drip, d1, Q3W, 6 cycles.
• Drug Trastuzumab
  8 mg/kg in Cycle 1, 6 mg/kg in subsequent cycles, intravenous drip, d1, Q3W, for 1 year.
• Drug Pertuzumab
  840mg in Cycle 1, 420mg in subsequent cycles, intravenous drip, d1, Q3W, for 1 year.

Primary outcome measures

• Occurrence of Grade 3/4 neutropenia [Time frame: Up to 24 weeks]

Secondary outcome measures (5)

• Neutrophil-related myeloprotective effects [Time frame: Up to 24 weeks]
• Red blood cell(RBC) -related myeloprotective effects [Time frame: Up to 24 weeks]
• Platelet-related myeloprotective effects [Time frame: Up to 24 weeks]
• Myeloprotective Effects [Time frame: Up to 24 months]
• Safety and tolerability [Time frame: Up to 24 months]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sun-yat sen university cancer center — Guangzhou

Identifiers

NCT: NCT05978648 · SMA-BC-002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗