The purpose of this study is to compare the safety and efficacy of bi-weekly WH002(Paclitaxel Medium and Long Chain Fat Emulsion Injection,Cholesterol Bound) vs Paclitaxel both followed by bi-weekly Epirubicin and Cyclophosphamide as neoadjuvant treatment in women with HER2-negative breast cancer.
This study is a multicenter, randomized, open-label, positive-drug parallel-controlled phase II trial. The primary aim of this study was to compare the safety, efficacy, and pharmacokinetics of a dose-dense regimen of bi-weekly WH002 followed by bi-weekly epirubicin and cyclophosphamide (ddWH002-ddEC) versus bi-weekly Paclitaxel® followed by bi-weekly EC (ddP-ddEC) as neoadjuvant treatment in women with HER2-negative high-risk early-stage and locally advanced breast cancer. Patients randomly assigned to ddP-ddEC received premedication with oral prednisolone (12 and 6 hours before paclitaxel), IV dexchlorpheniramine, and cimetidine or ranitidine (30 minutes before paclitaxel). Whereas all of these premedication was not required in the ddWH002-ddEC group before receiving WH002. Eligible subjects are those with biopsy-confirmed, HER2-negative breast cancer as verified by the research center, and whose tumor staging, as determined by imaging, falls into the categories of early high-risk (T1c-2, N1; T2, N0) or locally advanced (T1c-2, N2-3; T3-4, N0-3). Upon fulfilling all inclusion and exclusion criteria, participants will be randomized in a 1:1 ratio to either the WH002 followed by EC group (Group A) or the Paclitaxel® followed by EC group (Group B).Stratified randomization between the two groups based on tumor molecular subtypes: * Luminal type (HER2-negative, ER or progesterone receptor positive), * Triple-negative (HER2-negative, ER and progesterone receptor negative).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Group A(ddWH002-ddEC): Regimen for Group A during Cycles 1-Cycles 4:WH002, 260 mg/m² administered intravenously on Day 1, with a cycle length of 2 weeks (Q2W), repeated for a total of 4 cycles. Regimen for Group A during Cycles 5-Cycles 8: • Epirubicin Hydrochloride 90 mg/m² and Cyclophosphamide for Injection 600 mg/m², both administered intravenously on Day 1, with each cycle lasting 2 weeks (Q2W), continued for 4 consecutive cycles.
Group B (ddP-ddEC): Regimen for Group B during Cycles C1-C4: • Paclitaxel Injection (Paclitaxel®) 175 mg/m², administered intravenously on Day 1, with a cycle duration of 2 weeks (Q2W), repeated for a total of 4 cycles. Regimen for Group B during Cycles C5-C8: • Epirubicin Hydrochloride 90 mg/m² and Cyclophosphamide for Injection 600 mg/m², both administered intravenously on Day 1, with cycles recurring every 2 weeks (Q2W), for a series of 4 cycles.
National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Beijing, Beijing Municipality, China
All reported adverse events, serious adverse events and the percentage of drug-related adverse events, serious adverse events during the treatment period.
A summary of TEAEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported.Compare the safety and tolerability between the WH002 group and the Paclitaxel® group during the treatment period. Patients will be assessed for adverse events by clinical examination, questioning for symptoms of toxicity, laboratory assessments, vital signs, ECG and LVEF. Neurological toxicity and other toxicities will be assessed throughout the study according the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) Version 5.0.
Time frame: From the first administration of the medication until 28 days after the breast cancer surgery, or 28 days after the last administration of the medication.
pathologic Complete Response(pCR) Rate
Comparison of the overall pathological complete response rate (tpCR, defined as ypT0/ypTis ypN0) between the WH002 group and the Paclitaxel® group;
Time frame: the duration of 28 days of Postoperative of Breast Cancer;
pathologic Complete Response (pCR) and Breast Pathological Complete Response Rate(bpCR )
Comparison of the rates of pCR defined as ypT0 ypN0 and bpCR (ypT0/Tis) between the WH002 group and the Paclitaxel® group;
Time frame: the duration of 28 days of Postoperative Breast Cancer;
objective response rate(ORR)
Comparison of the objective response rate (ORR) assessed by ultrasound, mammography or MRI after paclitaxel treatment and sequential EC treatment between the WH002 group and the Paclitaxel® group;
Time frame: At the end of Cycle 2 (each cycle is 14 days); At the end of Cycle 4 (each cycle is 14 days);At the end of Cycle6 (each cycle is 14 days);At the end of Cycle 8 (each cycle is 14 days);
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time to peak concentration (Tmax)
Comparison of pharmacokinetic parameters of total and unbound paclitaxel between the WH002 group and the Paclitaxel® group following drug administration.
Time frame: the 1th day and 2th day of cycle 1 (each cycle is 14 days),the 1th day and 2th day of cycle 4 (each cycle is 14 days);
peak concentration (Cmax)
Comparison of pharmacokinetic parameters of total and unbound paclitaxel between the WH002 group and the Paclitaxel® group following drug administration.
Time frame: cycle 1(14 days)and cycle 4(14 days);
AUC0-inf
area under the concentration-time curve from time zero to the infinity. Comparison of pharmacokinetic parameters of total and unbound paclitaxel between the WH002 group and the Paclitaxel® group following drug administration.
Time frame: cycle 1(14 days)and cycle 4(14 days);
AUC0-t
area under the concentration-time curve from time zero to the last measurable .Comparison of pharmacokinetic parameters of total and unbound paclitaxel between the WH002 group and the Paclitaxel® group following drug administration.
Time frame: cycle 1(14 days)and cycle 4(14 days);
half-life (t½)
Comparison of pharmacokinetic parameters of total and unbound paclitaxel between the WH002 group and the Paclitaxel® group following drug administration.
Time frame: cycle 1(14 days)and cycle 4(14 days);
clearance (CL)
Comparison of pharmacokinetic parameters of total and unbound paclitaxel between the WH002 group and the Paclitaxel® group following drug administration.
Time frame: cycle 1(14 days)and cycle 4(14 days);
free fraction
ratio of free paclitaxel concentration to total paclitaxel concentration. Comparison of pharmacokinetic parameters of total and unbound paclitaxel between the WH002 group and the Paclitaxel® group following drug administration.
Time frame: cycle 1(14 days)and cycle 4(14 days);