Clinical trial NCT06802757: Posaconazole Plus Pembrolizumab and Chemotherapy vs Pembrolizumab and Chemotherapy in Neoadjuvant Therapy for Triple Negative Breast Cancer
Official title: A Phase II, Randomised, Open-label, Multicentre Study of Posaconazole Plus Pembrolizumab and Chemotherapy Versus Pembrolizumab and Chemotherapy as Neoadjuvant Therapy for Triple Negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Triple-Negative Breast Cancer
Pathological Complete Response
Neoadjuvant Therapy
Posaconazole
Lead sponsor: Shandong Cancer Hospital and Institute
Sponsor class: OTHER
First posted: 2025-01-31
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 40 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: 300 mg po bid, from Day 2, start maintenance dose at 300 mg po qd, q21d). 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Pathological Complete Response
timeFrame: 24 weeks
Secondary outcomes:
measure: Breast pathological complete response
timeFrame: 24 weeks
measure: Objective response rate
timeFrame: 24 weeks
measure: 3-year event-free survival rate
timeFrame: After a median follow-up of 3 years
measure: Survival rate
timeFrame: After a median follow-up of 3 years
measure: Security
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Jinan
country: China
facility: Breast Cancer Center Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences
state: Shandong
Study officials:
References: