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

Официальное название

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

Обзор

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.

Вмешательства

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

Первичные конечные точки

• Occurrence of Grade 3/4 neutropenia [Срок оценки: Up to 24 weeks]

Вторичные конечные точки (5)

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

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Sun-yat sen university cancer center — Гуанчжоу

Идентификаторы

NCT: NCT05978648 · SMA-BC-002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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