Optimal Application Timing of ADC Drugs for Advanced Breast Cancer

Официальное название

A Prospective, Randomized Controlled Phase II Trial Investigating the Optimal Timing of Antibody Drug Conjugates in Advanced HER2-Negative Breast Cancer Patients

Обзор

This study plans to initiate a prospective, randomized controlled trial to investigate the optimal timing of antibody drug conjugate (ADC) therapy in the management of advanced Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer. Primary Objective: To compare the difference in PFS2 (Time from randomization to disease progression after second therapy) between antibody-drug conjugate (ADC) followed by chemotherapy versus chemotherapy followed by ADC in the treatment of advanced HER2-negative breast cancer. Secondary Objectives: To compare overall survival (OS), adverse events, patient-reported outcomes, and cost-effectiveness between the two treatment sequences. Additionally, to identify potential biomarkers predictive of benefit from frontline ADC therapy.

Вмешательства

• Препарат Antibody drug conjugate
  The selection of ADC agents will be based on the patient's molecular subtype. For Hormone receptor (HR)+/HER2-low patients, anti-HER2 ADCs such as trastuzumab deruxtecan may be used. For HR+/HER2-zero patients, TROP-2-targeted ADCs such as sacituzumab govitecan are preferred. For HR-/HER2-low patients, either anti-HER2 ADCs or Trophoblast cell surface antigen 2 (TROP-2) ADCs may be considered. For HR-/HER2-zero patients, TROP-2 ADCs will be used. The specific ADC regimen will be determined at th
• Препарат Chemotherapy
  The chemotherapy regimen will consist of standard second-line agents such as capecitabine, eribulin, vinorelbine, or gemcitabine. The specific chemotherapy regimen will be determined at the discretion of the investigators.

Первичные конечные точки

• Progression-free survival 2 (PFS2) [Срок оценки: Up to approximately 20 months]

Вторичные конечные точки (4)

• Overall Survival (OS) [Срок оценки: Up to approximately 40 months]
• Patient-Reported Outcomes (PROs) [Срок оценки: Up to approximately 20 months]
• Time to Progression (TTP) [Срок оценки: Up to approximately 20 months]
• Adverse event [Срок оценки: Up to approximately 20 months]

Критерии участия

Критерии включения

• Female patients aged 18-75 years;
• Histologically confirmed advanced HER2-negative breast cancer, including IHC 2+/ISH-, IHC 1+/ISH-, and IHC 0/ISH- subtypes;
• Completed first-line combination chemotherapy for advanced/metastatic disease (specific regimen not restricted), with disease progression (PD) evaluated per RECIST criteria (HR-positive patients must have received at least one line of endocrine therapy);
• Electrocorticography (ECOG) performance status < 2;
• Estimated life expectancy ≥ 12 weeks;
• Adequate bone marrow function, defined as:

• ANC ≥ 1.5 × 10⁹/L
• Platelets ≥ 90 × 10⁹/L
• Hemoglobin ≥ 90 g/L
• Adequate hepatic and renal function, defined as:

• Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
• AST or ALT ≤ 2.5 × ULN (≤ 5 × ULN for patients with liver metastases)
• Creatinine clearance ≥ 60 mL/min
• Signed informed consent obtained prior to any study-related procedures or treatments, confirming the patient's willingness to participate and comply with study requirements.

Критерии исключения

• Prior treatment with an ADC after disease recurrence or metastasis;
• Pregnant or breastfeeding women;
• No evaluable recurrent or metastatic lesions as defined by RECIST 1.1 criteria;
• Symptomatic brain parenchymal and/or leptomeningeal metastases with symptoms not adequately controlled by treatment;
• History of other malignancies within the past 5 years, except for adequately treated carcinoma in situ of the cervix, cutaneous squamous cell carcinoma, or well-controlled localized basal cell carcinoma of the skin;
• Psychiatric disorders or other conditions that may interfere with patient compliance;
• Recent history of serious and uncontrolled systemic diseases, such as clinically significant cardiovascular disease, pulmonary disease, metabolic disorders, or arterial/venous thromboembolic events;
• Concurrent use of other investigational drugs, or participation in another clinical trial within 30 days prior to enrollment;
• Known or suspected allergy to any study drug or its excipients;
• Any other condition that, in the opinion of the investigator, renders the patient unsuitable for participation in this trial.

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

• Liaoning Cancer Hospital & Institute — Шэньян

Идентификаторы

NCT: NCT07657130 · OPTIMA-BC

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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