HER2 + Breast Cancer
Conditions
Keywords
BF-BOIN, Oral paclitaxel, Neoadjuvant Therapy, HER2 positive, Breast cancer
Brief summary
This is a multicenter, open-label, dose-finding 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 combined with anti-HER2 treatment. Eligible HER2-positive breast cancer patients receive 6 cycles of neoadjuvant THP regimen(paclitaxel oral solution + trastuzumab+pertuzumab) and are enrolled in three cohorts at oral paclitaxel dose levels 1-3 (125, 150, 175 mg/m²).
Interventions
COMBINATION_PRODUCTPaclitaxel oral solution plus Trastuzumab and Pertuzumab
Eligible patients in three cohorts receive 6 neoadjuvant THP cycles: paclitaxel oral solution at 125/150/175 mg/m² BID (D1, D8, D15), and dual anti-HER2 therapy - trastuzumab (8→6 mg/kg IV or 600 mg SC) and pertuzumab (840→420 mg IV), both Q3W - or, alternatively, the pertuzumab/trastuzumab SC fixed-dose combination (Phesgo; loading 1200/600 mg \[15 mL\], maintenance 600/600 mg \[10 mL\]), Q3W; all for 6 cycles.
Sponsors
Liu Shu
Study design
Allocation
NON_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 to 70 years. 2. 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). 3. HER2-positive status defined as IHC 3+ or IHC 2+ with FISH amplification. 4. Left ventricular ejection fraction (LVEF) ≥ 50%. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 6. Adequate organ function assessed within 14 days prior to first dose of study drug, without blood transfusion or growth-factor support, meeting the following: 1. Hematology: absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; platelet count (PLT) ≥ 100 × 10⁹/L; hemoglobin (Hb) ≥ 90 g/L. 2. 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. 7. Voluntary participation with signed informed consent, good compliance, and willingness to attend follow-up.
Exclusion criteria
1. History of prior invasive breast cancer. 2. Bilateral breast cancer, or inflammatory breast cancer (e.g., erythema and/or skin involvement and/or pathological evidence of tumor cells in dermal lymphatics). 3. Prior excisional and/or incisional biopsy of the primary tumor and/or axillary lymph nodes. 4. Prior systemic therapy for breast cancer. 5. History of life-threatening hypersensitivity reaction, or known allergy to any component of the study drug. 6. Participation in another drug or medical device clinical trial within 4 weeks prior to first dose, with receipt of investigational product or device. 7. Major surgery within 28 days prior to first dose, or planned major surgery during the study. 8. Other malignancy within the past 5 years (except cervical carcinoma in situ, non-melanoma skin cancer, localized prostate cancer, and ductal carcinoma in situ). 9. Active tuberculosis or other serious infectious disease, including but not limited to bacteremia, severe infectious pneumonia, or other severe infection requiring systemic therapy. 10. 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. 11. 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. 12. 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. 13. Uncontrolled concurrent illness or condition (including significant psychiatric or social condition) that, in the investigator's judgment, may affect compliance with study procedures. 14. 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. 15. 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. 16. 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. 17. Any other condition that, in the investigator's opinion, makes the subject unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose(MTD) | Up to 24 weeks. | The incidence of dose-limiting toxicitys and any AEs will be assessed. After the trial is completed, the MTD is determined with all the data based on isotonic regression by the shiny app "BF-BOIN" available at http://www.trialdesign.org. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| total Pathological Complete Response(tpCR) | Up to six months. | It refers to the absence of any invasive cancer in the resected specimens (breast + axilla) after completion of neoadjuvant chemotherapy and surgery (i.e., ypT0/is, ypN0). |
| Overall Response Rate(ORR) | Up to 24 weeks. | Response Evaluation Criteria in Solid Tumors (RECIST)：Progressive Disease (PD); Partial Response (PR); Complete Response (CR); Stable Disease (SD) Objective response rate (ORR), defined as the proportion of patients with a complete response (CR) partial response (PR) to treatment. |
Countries
China
Contacts
CONTACTShu Liu, PhD
CONTACTYu Ren, PhD
Outcome results
None listed