Trial Title:
Neoadjuvant Chemotherapy With WH002 in Women With HER2-negative Breast Cancer
NCT ID:
NCT06513364
Condition:
Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Paclitaxel
Albumin-Bound Paclitaxel
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
WH002
Description:
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.
Arm group label:
WH002
Other name:
Paclitaxel Medium/Long-chain Fat Emulsion Injection (Cholesterol-Conjugated)
Intervention type:
Drug
Intervention name:
paclitaxel injection
Description:
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.
Arm group label:
Paclitaxel Injection
Other name:
Taxol
Summary:
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.
Detailed description:
This study is a multicenter, randomized, open-label, positive-drug parallel-controlled
phase Ib 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).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥ 18 years, female;
2. Histologically confirmed, untreated, unilateral primary invasive breast cancer;
3. Confirmed as HER2-negative breast cancer based on pathology testing at the research
center; simultaneous determination of hormone receptor status (estrogen receptor
[ER] and progesterone receptor [PgR]), tumor grade, and Ki67 value;
4. Clinical staging based on imaging assessment meeting any of the following criteria:
IIA (T1c, N1; T2, N0), IIB (T2, N1; T3, N0), IIIA-IIIC (T1c-2, N2-3; T3, N1-3; T4,
any N);
5. Patient agrees to undergo breast cancer surgery after completing neoadjuvant
chemotherapy;
6. The Eastern Cooperative Oncology Group performance status ≤1;
7. Essentially normal function of major organs, with laboratory test values during
screening conforming to the following standards:
System Laboratory Test Values Hematology Absolute Neutrophil Count ≥1.5×10^9/L
Platelets ≥100×10^9/L Hemoglobin ≥100g/L Kidney Serum Creatinine (Cr) ≤1.5×ULN or
Creatinine Clearance (CCr) ≥60 mL/min (calculated using the Cockcroft-Gault formula)
Liver Total Bilirubin (serum) ≤1.5×ULN Aspartate Aminotransferase and Alanine
Aminotransferase ≤2.5×ULN Coagulation International Normalized Ratio (INR) or
Prothrombin Time (PT) ≤1.5×ULN, unless the subject is on anticoagulant therapy；
8. Echocardiographic assessment: Left Ventricular Ejection Fraction (LVEF) ≥50%;
9. For patients of childbearing potential: Patients must agree to effective
contraception during the treatment period and for at least 90 days after the last
dose of study treatment, adopting double-barrier contraceptive methods, such as
condoms, oral or injectable contraceptives, intrauterine devices, etc.;
10. Voluntarily signs the informed consent form, demonstrating good compliance.
Exclusion Criteria:
1. Patients with stage IV metastatic breast cancer or those deemed by the investigator
as ineligible for curative surgical resection following neoadjuvant therapy;
2. Inflammatory breast cancer and bilateral primary breast cancer (including invasive
and in situ carcinomas).
3. Patients requiring concurrent use of medications that may affect the metabolism of
the study drug within 2 weeks prior to enrollment or during the study, such as
strong CYP2C8 or CYP3A4 inducers or inhibitors;
4. Breast cancer patients who have previously received anti-tumor treatments, including
radiotherapy, chemotherapy, endocrine therapy, targeted therapy, immunotherapy, or
who have undergone breast surgery (excluding diagnostic biopsy for primary breast
cancer);
5. Patients who must receive additional anti-tumor therapies other than the
investigational product during the study, such as chemotherapy, endocrine therapy,
targeted therapy, immunotherapy regimens, or radiotherapy;
6. Patients with a history of allergic constitution (excluding mild, asymptomatic
seasonal allergies), or known hypersensitivity to taxane drugs/WH002 or its
excipients [e.g., allergy to medications containing polyoxyethylated castor oil
(like cyclosporine); or allergy to drugs containing hardened castor oil (such as
vitamin injections); or allergy to lipid emulsion-based drugs], or known allergy to
epirubicin, cyclophosphamide, and/or their excipients;
7. Patients with severe organ dysfunction (heart, lung, liver, kidney, brain, etc.), or
those who have experienced severe cardiovascular events within 6 months prior to
dosing, such as myocardial infarction, unstable angina, coronary artery bypass or
peripheral arterial bypass graft surgery, congestive heart failure, significant
cerebrovascular events (including transient ischemic attacks), or have arrhythmias
requiring treatment, confirmed prolongation of QTc interval (≥470ms) upon
reassessment, and chronic heart failure patients (NYHA class III and IV); poorly
controlled diabetes (fasting blood glucose ≥13.3mmol/L); inadequately controlled
hypertension (systolic pressure >160 mmHg or diastolic pressure >100 mmHg), etc.;
8. Patients who have had or concurrently have other malignant tumors within the past 5
years, excluding those with basal cell or squamous cell carcinoma of the skin
treated with curative intent, or cervical carcinoma in situ;
9. Patients with active infections requiring intravenous antibiotic treatment;
10. Women of childbearing potential who are pregnant, breastfeeding, or have a positive
pregnancy test;
11. History of motor or sensory neuropathy from any cause (greater than NCI-CTCAE V5.0
Grade 1) prior to enrollment;
12. Participation in another clinical trial within 4 weeks prior to enrollment;
13. Any condition, as judged by the investigator, that makes the subject unsuitable for
participation in this clinical study.
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Address:
City:
Beijing
Zip:
100021
Country:
China
Contact:
Last name:
Jiani Wang, MD
Phone:
+86-18600162870
Email:
ncc_wangjiani@126.com
Investigator:
Last name:
Fei Ma, MD
Email:
Principal Investigator
Investigator:
Last name:
Jiani Wang, MD
Email:
Sub-Investigator
Start date:
July 30, 2024
Completion date:
October 31, 2025
Lead sponsor:
Agency:
Beijing Wehand-Bio Pharmaceutical Co., Ltd
Agency class:
Industry
Collaborator:
Agency:
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Agency class:
Other
Source:
Beijing Wehand-Bio Pharmaceutical Co., Ltd
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06513364
