Breast Cancer
Conditions
Keywords
Triple-Negative Breast Cancer, Pathological Complete Response, Neoadjuvant Therapy, Posaconazole
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.
Interventions
DRUGPosaconazole
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.
DRUGNab-paclitaxel
Nab-paclitaxel 260mg/m2 d1 q21d
DRUGCarboplatin
Carboplatin AUC=5-6 d1 q21d
DRUGAnthracycline
Epirubicin 90-100mg/m2 d1 q21d or Doxorubicin 50-60mg/m2 d1 q21d
DRUGCyclophosphamide
Cyclophosphamide 1000mg/m2 d1 q21d
DRUGPD-1 inhibitors
Toripalimab, Pembrolizumab and Camrelizumab, etc.
Sponsors
Shandong Cancer Hospital and Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Female, aged ≥ 18 and ≤ 70 years old; 2. first-confirmed TNBC; 3. cT1cN1-3M0 or cT2-4N0-3M0; 4. ECOG score 0-1 points.
Exclusion criteria
1. Stage I or IV; 2. History of previous breast cancer; 3. Patients with a history of other tumors who have received systemic therapy or local radiotherapy; 4. No immune system disease or connective tissue disease; 5. No history of hormone therapy; 6. Pregnant/lactating.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Complete Response | 24 weeks | Expected 25% increase in pCR rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 |
Countries
China
Contacts
CONTACTPengfei Qiu, MD
CONTACTZhiqiang Shi, MD
Outcome results
None listed