Kumorixilib Plus Capecitabine and Letrozole for Neoadjuvant Treatment of HR-Positive HER2-Negative Breast Cancer

Официальное название

An Exploratory Study to Evaluate the Efficacy and Safety of Kumorixilib Combined With Capecitabine and Letrozole as Neoadjuvant Therapy for HR-Positive, HER2-Negative Breast Cancer

Обзор

This study is a single-center, prospective, open-label exploratory clinical study to assess the efficacy and safety of kumorixilib combined with capecitabine and letrozole as neoadjuvant therapy in patients with HR+/HER2- stage II-III invasive breast cancer. The study plans to enroll 35 eligible patients, and all participants will receive the triple-drug combination regimen without randomization. The treatment regimen: kumorixilib 180 mg orally once daily, capecitabine 500 mg orally three times daily, and letrozole 2.5 mg orally once daily; each cycle lasts 28 days, for a total of 6 cycles. Breast MRI will be used to evaluate radiological tumor response. Surgical resection will be arranged 2-4 weeks after neoadjuvant treatment ends. The primary endpoint is the percentage change in Ki-67 score from baseline to Cycle 1 Day 28. Secondary endpoints include the complete cell cycle arrest rate (CCCA, Ki-67 ≤ 2.7%) on Day 28, the reduction rate of functional tumor volume (FTV), the proportion of patients with RCB 0-1, objective response rate (ORR), and treatment safety. Treatment will be discontinued upon disease progression, intolerable adverse events, withdrawal of consent, or investigator judgment.

Вмешательства

• Препарат Kumorixilib 180mg
  Kumorixilib: 180 mg orally once daily. One cycle lasts 28 consecutive days. The total treatment duration is 6 cycles.
• Препарат Capecitabine 500mg
  Capecitabine: 500 mg orally three times daily. One cycle lasts 28 consecutive days. The total treatment duration is 6 cycles.
• Препарат Letrozole 2.5mg
  Letrozole: 2.5 mg orally once daily. One cycle lasts 28 consecutive days. The total treatment duration is 6 cycles.

Первичные конечные точки

• Percentage change in Ki-67 score from baseline to Cycle 1 Day 28 [Срок оценки: At the end of Cycle 1 (each cycle is 28 days)]

Вторичные конечные точки (5)

• Complete cell cycle arrest (CCCA) rate at Cycle 1 Day 28 [Срок оценки: At the end of Cycle 1 (each cycle is 28 days)]
• Reduction rate of functional tumor volume (FTV) [Срок оценки: At the end of Cycle 6 (each cycle is 28 days), before breast surgery]
• Incidence of Residual Cancer Burden (RCB) 0-1 [Срок оценки: After surgical resection (end of neoadjuvant treatment)]
• Objective Response Rate (ORR) [Срок оценки: At the end of Cycle 6 (each cycle is 28 days), before breast surgery]
• Treatment-related adverse events [Срок оценки: From treatment initiation up to 30 days after the last dose]

Критерии участия

Критерии включения

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Patients who meet all of the following inclusion criteria are eligible for enrollment in this trial:

• Female patients with breast cancer aged ≥18 and ≤75 years, satisfying one of the following menopausal status criteria: (1) Bilateral oophorectomy in medical history, or age ≥60 years; (2) Age <60 years with natural menopause (defined as spontaneous cessation of regular menses for at least 12 consecutive months without other pathological or physiological causes), with postmenopausal levels of E2 and FSH; (3) Pre-menopausal or peri-menopausal female patients who are willing to receive LHRH agonist therapy throughout the study period.
• Histopathologically confirmed estrogen receptor (ER)-positive (>10%) and/or progesterone receptor (PR)-positive (>10%), HER2-negative breast cancer, assessed in accordance with the 2018 ASCO-CAP guidelines. HER2 negativity is defined as immunohistochemistry (IHC) score of 0+, or IHC 2+ with negative in situ hybridization (ISH) test (ISH amplification ratio <2.0), verified by the pathological laboratory.
• Accept core needle biopsy to provide initial tissue samples with Ki-67 ≥10% tested on the initial specimen; agree to provide tissue samples for tumor biomarker testing and peripheral blood samples for biomarker analysis.
• Treatment-naïve breast cancer patients staged as Stage II-III per the 8th edition of the AJCC staging system.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Adequate organ function as defined below: Hematologic function: ① Absolute neutrophil count (ANC) ≥1.5×10⁹/L (no growth factor administered within 14 days prior to screening); ② Platelet count ≥100×10⁹/L (no corrective hematologic therapy within 7 days prior to screening); ③ Hemoglobin ≥100 g/L (no corrective hematologic therapy within 7 days prior to screening).

Hepatic and renal function: ① Total bilirubin ≤1×upper limit of normal (ULN); ② Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3×ULN (ALT and AST ≤5×ULN for patients with liver metastases); ③ Blood urea nitrogen and serum creatinine ≤1.5×ULN, with creatinine clearance ≥50 mL/min (calculated by the Cockcroft-Gault formula).

• Cardiac function on echocardiogram: left ventricular ejection fraction (LVEF) ≥50%. 12-lead electrocardiogram (ECG): QT interval ≤480 ms.
• Able to provide written informed consent prior to any study-related procedures.

Критерии исключения

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Patients presenting with any of the following conditions are ineligible for enrollment in this study:

• Prior receipt of any form of anti-tumor therapy (including chemotherapy, radiotherapy, molecular targeted therapy, endocrine therapy, etc.).
• Concurrent administration of other anti-tumor agents.
• Bilateral breast cancer, inflammatory breast cancer, or occult breast cancer.
• Stage IV breast cancer.
• Breast cancer without histopathological confirmation, or refusal to undergo breast core needle biopsy before or during study treatment.
• History of other malignant tumors within the previous 5 years, except for cured carcinoma in situ of the cervix.
• Severe dysfunction of vital organs including the heart, liver and kidneys.
• Conditions interfering with oral drug intake and absorption, such as inability to swallow, chronic diarrhea, or intestinal obstruction.
• Participation in another interventional clinical trial within 4 weeks prior to enrollment.
• Known hypersensitivity to any components of the study regimen; history of immunodeficiency diseases, including positive human immunodeficiency virus (HIV) test, hepatitis C virus infection, active hepatitis B virus infection, other acquired or congenital immunodeficiency disorders, or a history of organ transplantation.
• Prior diagnosis of any cardiac disease, including clinically significant arrhythmias requiring medical intervention, myocardial infarction, heart failure, or any other cardiac disease judged by the investigator to render the patient unsuitable for trial participation.
• Pregnant or breastfeeding female patients; fertile women with a positive baseline pregnancy test result, or fertile women unwilling to use effective contraception throughout the entire trial period.
• Coexisting severe medical conditions that may compromise patient safety or interfere with study completion as assessed by the investigator, including but not limited to uncontrolled severe hypertension, uncontrolled severe diabetes, active infections, etc.
• Confirmed prior history of neurological or psychiatric disorders, including epilepsy or dementia.
• Any other conditions deemed by the investigator to make the patient unsuitable 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

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 3 центра

• Fujian Cancer Hospital — Фучжоу
• Fujian Provincial Hospital — Фучжоу
• The Second Affiliated Hospital of Fujian Medical University — Quanzhou

Идентификаторы

NCT: NCT07691333 · K2026-277-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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