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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Chemotherapy + PD-1 inhibitors | Other | Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with PD-1 inhibitors |
|
| Chemotherapy + PD-1 inhibitors+Posaconazole | Experimental | Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with PD-1 inhibitors and posaconazole |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Posaconazole | Drug | 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. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pathological Complete Response | Expected 25% increase in pCR rate | 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Breast pathological complete response | 24 weeks | |
| Objective response rate | 24 weeks | |
| 3-year event-free survival rate |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Pengfei Qiu, MD | Contact | +86053167626215 | qiu.pf@outlook.com | |
| Zhiqiang Shi, MD | Contact | +86053167626215 | shizhiqiang1024@163.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Breast Cancer Center Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences | Recruiting | Jinan | Shandong | 250117 | China |
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| Nab-paclitaxel | Drug | Nab-paclitaxel 260mg/m2 d1 q21d |
|
| Carboplatin | Drug | Carboplatin AUC=5-6 d1 q21d |
|
| Anthracycline | Drug | Epirubicin 90-100mg/m2 d1 q21d or Doxorubicin 50-60mg/m2 d1 q21d |
|
| Cyclophosphamide | Drug | Cyclophosphamide 1000mg/m2 d1 q21d |
|
| PD-1 inhibitors | Drug | Toripalimab, Pembrolizumab and Camrelizumab, etc. |
|
| After a median follow-up of 3 years |
| Survival rate | After a median follow-up of 3 years |
| Security | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | 24 weeks |
|
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D064726 | Triple Negative Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| C101425 | posaconazole |
| C520255 | 130-nm albumin-bound paclitaxel |
| D016190 | Carboplatin |
| D018943 | Anthracyclines |
| D003520 | Cyclophosphamide |
| D000082082 | Immune Checkpoint Inhibitors |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D000074322 | Antineoplastic Agents, Immunological |
| D000970 | Antineoplastic Agents |
| D045506 | Therapeutic Uses |
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