Neoadjuvant Treatment Pegylated Liposomal Doxorubicin Plus Cyclophosphamide Sequential Docetaxel Plus Trastuzumab and Pertuzumab Versus Docetaxel Plus Carboplatin Combined With Trastuzumab and Pertuzumab in HER-2 Positive Breast Cancer

Официальное название

A Multicentre, Open-label, Randomised Trial of Neoadjuvant Pegylated Liposomal Doxorubicin Plus Cyclophosphamide Sequential Docetaxel Plus Trastuzumab and Pertuzumab Versus Docetaxel Plus Carboplatin Combined With Trastuzumab and Pertuzumab in HER-2 Positive Breast Cancer

Обзор

This is a multicenter, open label, non-inferiority, randomized controlled clinical study. The aim of this study is to evaluate the efficacy and safety of a pegylated liposomal doxorubicin + cyclophosphamide followed by docetaxel plus trastuzumab and pertuzumab (PLD + C + HP followed by THP) regimen compared with a docetaxel + carboplatin plus trastuzumab and pertuzumab (TCbHP) regimen in the neoadjuvant treatment of HER-2-positive breast cancer.

Вмешательства

• Препарат pegylated liposomal doxorubicin (PLD)
  pegylated liposomal doxorubicin (PLD) 30 mg/m\^2, i.v., d1, q3w
• Препарат cyclophosphamide (C)
  cyclophosphamide (C) 600 mg/m\^2, i.v., d1, q3w
• Препарат trastuzumab (H)
  trastuzumab (H) 8 mg/kg loading dose, 6 mg/kg maintenance doses, i.v., d1, q3w
• Препарат pertuzumab (P)
  pertuzumab (P) 840 mg loading dose, 420 mg maintenance doses, i.v., d1, q3w
• Препарат docetaxel (T)
  docetaxel (T) 90\~100 mg/m\^2, i.v., d1, q3w
• Препарат docetaxel (T)
  docetaxel (T) 75 mg/m\^2, i.v., d1, q3w
• Препарат carboplatin (Cb)
  carboplatin (Cb) AUC 6, i.v., d1, q3w
• Препарат trastuzumab (H)
  trastuzumab (H) 8 mg/kg loading dose, 6 mg/kg maintenance doses, i.v., d1, q3w
• Препарат pertuzumab (P)
  pertuzumab (P) 840 mg loading dose, 420 mg maintenance doses, i.v., d1, q3w

Первичные конечные точки

• Pathological complete response (pCR) rate [Срок оценки: Within 2 to 5 weeks after completion of neoadjuvant therapy]

Вторичные конечные точки (7)

• Objective response rate (ORR) at the end of neoadjuvant chemotherapy [Срок оценки: After the last dose to before surgery or within 21 days]
• 5-year disease-free survival (DFS) rate [Срок оценки: 5 years]
• Breast conservation rate at surgery [Срок оценки: Within 2 to 5 weeks after completion of neoadjuvant therapy]
• Number of participants with treatment-related adverse events as assessed by NCI-CTCAE V5.0, including overall and Grade 3/4 adverse events. [Срок оценки: 5 years]
• Percentage of Participants with dose reductions of chemotherapy due to Grade 3/4 adverse events as assessed by NCI-CTCAE V5.0 [Срок оценки: 1 year]
• Percentage of Participants with chemotherapy delay due to Grade 3/4 adverse events as assessed by NCI-CTCAE V5.0 [Срок оценки: 1 year]
• Relative dose intensity (RDI) [Срок оценки: 1 year]

Критерии участия

Критерии включения

• Female patients aged from 18 to 70 years old;
• Histologically confirmed as invasive breast cancer and without previous treatment.;
• HER-2 Positive (defined by IHC 3+ or ISH positive);
• Tumor > 2cm;
• Biopsy pathology (FNAB or CNB) diagnosed regional lymph node metastasis within 28 days prior to randomization;
• Participants must have at least one measurable disease according to RECIST 1.1.
• Participants with multifocal tumors (more than one tumor confined to the same quadrant as the primary tumor) are eligible provided all discrete lesions are sampled and centrally confirmed as HER2 positive.
• Operable breast cancer with cT2-cT4/cN1-cN3/cM0, according to the AJCC tumor staging manual (8th Edition).
• The HR(ER and PR) status of the primary tumor and the expression level of Ki-67 are clear.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• LVEF ≥ 55%;
• Brain natriuretic peptide (BNP) (or N-terminal pro brain natriuretic peptide (NT proBNP)) and cardiac troponin assays were within normal values.
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and serum total bilirubin are all ≤2 ULN. Serum creatinine ≤ 1.5 ULN.
• Bone marrow function: white blood cell counts ≥ 3.0x10\^9/L, absolute neutrophil counts (ANC) ≥ 1.5x10\^9/L, platelets ≥ 100x10\^9/L, hemoglobin ≥ 90g/L;
• Participants had good compliance with the planned treatment and follow-up, understood the study procedures of this study, and signed informed consent form.

Критерии исключения

• Breast cancer with distant metastasis;
• Participants with multiple lesions (in different quadrants) or bilateral breast cancer;
• Participants who have received prior anti-cancer therapy for breast cancer except those participants with a history of breast lobular carcinoma in situ (LCIS) that was surgically managed or ductal carcinoma in situ (DCIS) treated exclusively with mastectomy. In case of prior history of LCIS/DCIS, >5 years must have passed from surgery until diagnosis of current breast cancer;
• In the past and present, participants with severe cardiac disease or discomfort , including but not limited: 1)High-risk uncontrolled arrhythmia, atrial tachycardia (heart rate > 100/min in resting state), significant ventricular arrhythmia (ventricular arrhythmia) or higher atrioventricular block (second-degree type 2 \[Mobitz 2\] atrioventricular block or third-degree atrioventricular block); 2)Angina pectoris requiring anti-angina medication; 3)Clinically significant valvular heart disease; 4)ECG showing transmural myocardial infarction; 5)Uncontrolled hypertension (eg systolic blood pressure > 180mm Hg or diastolic blood pressure > 100mmHg); 6)Myocardial infarction; 7)Congestive heart failure;
• Participants have the following serious illnesses or medical conditions, including but not limited: 1)History of serious neurological or psychiatric disorders, including psychosis, dementia, or epilepsy, that prevent understanding and informed consent; 2)Active uncontrolled infection; 3)Active peptic ulcer, unstable diabetes;
• A history of other malignancies within the previous 5 years, except for adequately treated carcinoma in situ of the cervix or basal cell carcinoma of the skin;
• Treatment with any investigational drug within 28 days prior to randomization;
• Participants who are known to be allergic to the active or other components of the study treatment or have contraindications for surgery;
• Participants who are pregnant, breastfeeding, or refuse to use adequate contraception prior to study entry and for the duration of study participation;
• Participants who were judged by the investigator to be unsuitable for this study.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Sunyat-sen Memorial Hospital — Guandong

Идентификаторы

NCT: NCT05159193 · CSPC-DMS-BC-K07

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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