Paclitaxel Oral Solution in Triple Neagtive Breast Cancer Neoadjuvant Therapy: A Dose-Finding Study

Official title

A Dose-Finding Study of Paclitaxel Oral Solution in Neoadjuvant Therapy for Patients With Triple Negative Breast Cancer

Overview

This is a multicenter, open-label, dose-escalation trial using a backfill Bayesian optimal interval (BF-BOIN) design to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) for paclitaxel oral solution followed by epirubicin plus cyclophosphamide therapy. Eligible triple-negative breast cancer patients are enrolled in three cohorts at oral paclitaxel dose levels 1-3 (125, 150, 175 mg/m²).

Interventions

• Drug Epirubicin and cyclophosphamide followed by paclitaxel oral solution
  Cycles 1-4: Epirubicin 90 mg/m² plus cyclophosphamide 600 mg/m² by intravenous infusion on day 1 (D1) of each cycle; one treatment cycle administered every 3 weeks. Cycles 5-8: Paclitaxel oral solution 125, 150, or 175 mg/m², given twice daily on days 1, 8, and 15 of each cycle; one cycle every 3 weeks.

Primary outcome measures

• Maximum Tolerated Dose(MTD) [Time frame: Up to approximately 30 weeks]

Secondary outcome measures (2)

• total Pathological Complete Response(tpCR) [Time frame: Up to approximately 30 weeks.]
• Overall Response Rate(ORR) [Time frame: Up to approximately 30 weeks.]

Eligibility criteria

Inclusion criteria

• Female, aged 18 to 70 years.
• Histologically confirmed invasive breast cancer by core needle biopsy; clinical stage T1c-4, N0-3, M0 per the AJCC 8th edition breast cancer staging system (T1cN0M0 excluded).
• Triple-negative breast cancer (TNBC) is defined as ER <1%, PR <1%, and HER2-negative \[IHC 0, IHC 1+, or IHC 2+ with FISH-negative\].
• Left ventricular ejection fraction (LVEF) ≥ 50%.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function assessed within 14 days prior to first dose of study drug, without blood transfusion or growth-factor support, meeting the following:

• Hematology: absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; platelet count (PLT) ≥ 100 × 10⁹/L; hemoglobin (Hb) ≥ 90 g/L.
• Blood chemistry: total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 × ULN; blood urea nitrogen (BUN) and creatinine (Cr) ≤ 1.5 × ULN; creatinine clearance (CrCl) ≥ 50 mL/min by the Cockcroft-Gault formula.
• Voluntary participation with signed informed consent, good compliance, and willingness to attend follow-up.

Exclusion criteria

• History of prior invasive breast cancer.
• Bilateral breast cancer, or inflammatory breast cancer (e.g., erythema and/or skin involvement and/or pathological evidence of tumor cells in dermal lymphatics).
• Prior excisional and/or incisional biopsy of the primary tumor and/or axillary lymph nodes.
• Prior systemic therapy for breast cancer.
• History of life-threatening hypersensitivity reaction, or known allergy to any component of the study drug.
• Participation in another drug or medical device clinical trial within 4 weeks prior to first dose, with receipt of investigational product or device.
• Major surgery within 28 days prior to first dose, or planned major surgery during the study.
• Other malignancy within the past 5 years (except cervical carcinoma in situ, non-melanoma skin cancer, localized prostate cancer, and ductal carcinoma in situ).
• Active tuberculosis or other serious infectious disease, including but not limited to bacteremia, severe infectious pneumonia, or other severe infection requiring systemic therapy.
• History of immunodeficiency or other autoimmune disease, including but not limited to HIV infection (positive HIV antibody), systemic lupus erythematosus, rheumatoid arthritis, or history of organ transplantation.
• History of any of the following cardiovascular/cerebrovascular diseases: (1) unstable angina; (2) clinically significant or medication-requiring arrhythmia; (3) myocardial infarction within 6 months; (4) heart failure, or second-degree or higher atrioventricular block; (5) cerebral infarction (except lacunar infarction) or cerebral hemorrhage within 6 months.
• Uncontrolled hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg despite regular antihypertensive medication), or history of hypertensive crisis or hypertensive encephalopathy.
• Uncontrolled concurrent illness or condition (including significant psychiatric or social condition) that, in the investigator's judgment, may affect compliance with study procedures.
• Requirement for long-term use of proton pump inhibitors or H2 receptor antagonists during the study; or use of strong inducers or inhibitors of CYP3A4 or CYP2C8 within 2 weeks prior to first study-drug administration.
• In the investigator's judgment, subjects unsuitable or unwilling to take oral study drug: (1) clinically significant or uncontrolled congenital or acquired gastrointestinal disease; (2) diagnosed disease that may affect administration, gastrointestinal transit, or absorption of the study drug, or adherence to oral study drug, including intestinal obstruction and inflammatory bowel disease (Crohn's disease and ulcerative colitis), peptic ulcer, uncontrolled nausea, vomiting, or diarrhea; (3) presence or suspected impairment of bile secretion.
• Pregnant or lactating women; women of childbearing potential with a positive pregnancy test at screening; or those unwilling to use effective contraception throughout the study and for 3 months after the last dose.
• Any other condition that, in the investigator's opinion, makes the subject unsuitable for enrollment.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The Affiliated Hospital of Guizhou Medical University — Guiyang

Identifiers

NCT: NCT07739485 · OT-2005-003

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗