Posaconazole Plus PD-1 Inhibitors and Chemotherapy vs PD-1 Inhibitors and Chemotherapy in Neoadjuvant Therapy for Triple Negative Breast Cancer

Официальное название

A Phase II, Randomised, Open-label, Multicentre Study of Posaconazole Plus PD-1 Inhibitors and Chemotherapy Versus PD-1 Inhibitors and Chemotherapy as Neoadjuvant Therapy for Triple Negative Breast Cancer

Обзор

Triple-negative breast cancer (TNBC) is as sociated with shorter overall survival than other breast cancer subtypes, despite the use of curative-intent anthracycline- and taxane-based systemic chemotherapy. Neoadjuvant therapy is now also recognized as the standard treatment for patients with high-risk TNBC. The Keynote-522 study demonstrated that the application of pembrolizumab has raised the pathological Complete Response (pCR) rate in TNBC to over 60%, but nearly 40% of patients still do not achieve pCR. How to further improve the pCR rate in TNBC patients has become a hot topic of current research. Posaconazole is an antibiotic used to prevent invasive Aspergillus and Candida infections and to treat oropharyngeal candidiasis. Our preclinical studies have found that posaconazole can inhibit immune cell-mediated steroidogenesis to restrict TNBC tumor progression. The investigators design and begin a a prospective randomized controlled clinical study to explore the effectiveness of posaconazole in the neoadjuvant treatment of TNBC.

Подробное описание

OBJECTIVES: On the basis of chemotherapy combined with immunotherapy, posaconazole was used to further improve the pathological complete response (pCR) rate of high-risk triple-negative breast cancer (TNBC), and to explore biomarkers.

OUTLINE: From february 1st, 2025 to june 30th, 2026 the investigators will recruit 72 patients with first-time diagnosed early-stage TNBC. Enrolled patients were randomly divided into experimental group and control group on a 1:1 basis. Both groups received standard neoadjuvant chemotherapy combined with immunotherapy. The experimental group was treated with posaconazole (Day 1 of Cycle 1 only: 300 mg bid; from Day 2, maintenance dose of 300 mg qd, oral administration. 21 days per treatment cycle, for a total of 8 cycles.). Standard surgical treatment was performed after 8 cycles and the surgical specimens were pathologically tested to compare the differences in pCR rates between the two groups.

Вмешательства

• Препарат Posaconazole
  Day 1 of Cycle 1 only: 300 mg bid; from Day 2, maintenance dose of 300 mg qd, oral administration. 21 days per treatment cycle, for a total of 8 cycles.
• Препарат Nab-paclitaxel
  Nab-paclitaxel 260mg/m2 d1 q21d
• Препарат Carboplatin
  Carboplatin AUC=5-6 d1 q21d
• Препарат Anthracycline
  Epirubicin 90-100mg/m2 d1 q21d or Doxorubicin 50-60mg/m2 d1 q21d
• Препарат Cyclophosphamide
  Cyclophosphamide 1000mg/m2 d1 q21d
• Препарат PD-1 inhibitors
  Toripalimab, Pembrolizumab and Camrelizumab, etc.

Первичные конечные точки

• Pathological Complete Response [Срок оценки: 24 weeks]

Вторичные конечные точки (5)

• Breast pathological complete response [Срок оценки: 24 weeks]
• Objective response rate [Срок оценки: 24 weeks]
• 3-year event-free survival rate [Срок оценки: After a median follow-up of 3 years]
• Survival rate [Срок оценки: After a median follow-up of 3 years]
• Security [Срок оценки: 24 weeks]

Критерии участия

Критерии включения

• Female, aged ≥ 18 and ≤ 70 years old;
• first-confirmed TNBC;
• cT1cN1-3M0 or cT2-4N0-3M0;
• ECOG score 0-1 points.

Критерии исключения

• Stage I or IV;
• History of previous breast cancer;
• Patients with a history of other tumors who have received systemic therapy or local radiotherapy;
• No immune system disease or connective tissue disease;
• No history of hormone therapy;
• Pregnant/lactating.

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

• Breast Cancer Center Shandong Cancer Hospital and Institute Shandong First Medical Univers — Цзинань

Идентификаторы

NCT: NCT06802757 · POS-PEM-Ⅱ-NEO-TNBC

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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