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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Pathological Complete Response
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female, aged ≥ 18 and ≤ 70 years old;
- •first-confirmed TNBC;
- •cT1cN1-3M0 or cT2-4N0-3M0;
- •ECOG score 0-1 points.
排除标准
- •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.
研究组 & 干预措施
Chemotherapy + PD-1 inhibitors
Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with PD-1 inhibitors
干预措施: Anthracycline (Drug)
Chemotherapy + PD-1 inhibitors
Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with PD-1 inhibitors
干预措施: Carboplatin (Drug)
Chemotherapy + PD-1 inhibitors
Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with PD-1 inhibitors
干预措施: Cyclophosphamide (Drug)
Chemotherapy + PD-1 inhibitors+Posaconazole
Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with PD-1 inhibitors and posaconazole
干预措施: Posaconazole (Drug)
Chemotherapy + PD-1 inhibitors
Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with PD-1 inhibitors
干预措施: PD-1 inhibitors (Drug)
Chemotherapy + PD-1 inhibitors+Posaconazole
Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with PD-1 inhibitors and posaconazole
干预措施: Anthracycline (Drug)
Chemotherapy + PD-1 inhibitors+Posaconazole
Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with PD-1 inhibitors and posaconazole
干预措施: PD-1 inhibitors (Drug)
Chemotherapy + PD-1 inhibitors+Posaconazole
Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with PD-1 inhibitors and posaconazole
干预措施: Nab-paclitaxel (Drug)
Chemotherapy + PD-1 inhibitors+Posaconazole
Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with PD-1 inhibitors and posaconazole
干预措施: Cyclophosphamide (Drug)
Chemotherapy + PD-1 inhibitors+Posaconazole
Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with PD-1 inhibitors and posaconazole
干预措施: Carboplatin (Drug)
Chemotherapy + PD-1 inhibitors
Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with PD-1 inhibitors
干预措施: Nab-paclitaxel (Drug)
结局指标
主要结局
Pathological Complete Response
时间窗: 24 weeks
Expected 25% increase in pCR rate
次要结局
- Breast pathological complete response(24 weeks)
- Objective response rate(24 weeks)
- 3-year event-free survival rate(After a median follow-up of 3 years)
- Survival rate(After a median follow-up of 3 years)
- Security(24 weeks)
研究者
Yongsheng Wang
Professor
Shandong Cancer Hospital and Institute