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
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Enrollment
- 72
- Locations
- 1
- Primary Endpoint
- Pathological Complete Response
Study Overview
Brief Summary
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.
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Female, aged ≥ 18 and ≤ 70 years old;
- •first-confirmed TNBC;
- •cT1cN1-3M0 or cT2-4N0-3M0;
- •ECOG score 0-1 points.
Exclusion Criteria
- •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.
Arms & Interventions
Chemotherapy + PD-1 inhibitors
Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with PD-1 inhibitors
Intervention: Anthracycline (Drug)
Chemotherapy + PD-1 inhibitors
Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with PD-1 inhibitors
Intervention: Carboplatin (Drug)
Chemotherapy + PD-1 inhibitors
Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with PD-1 inhibitors
Intervention: 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
Intervention: Posaconazole (Drug)
Chemotherapy + PD-1 inhibitors
Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with PD-1 inhibitors
Intervention: 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
Intervention: 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
Intervention: 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
Intervention: 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
Intervention: 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
Intervention: Carboplatin (Drug)
Chemotherapy + PD-1 inhibitors
Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with PD-1 inhibitors
Intervention: Nab-paclitaxel (Drug)
Outcomes
Primary Outcomes
Pathological Complete Response
Time Frame: 24 weeks
Expected 25% increase in pCR rate
Secondary Outcomes
- 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)
Investigators
Yongsheng Wang
Professor
Shandong Cancer Hospital and Institute