Comparing the Efficacy of Nab-PHP and TCbHP in Neoadjuvant Therapy for HER2 Positive Operable Breast Cancer

Study Overview
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Brief Summary
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At present, trastuzumab combined with patuzumab has become the standard neoadjuvant therapy for high-risk HER2 positive breast cancer. TCbHP has been the standard choice of neoadjuvant therapy for HER2 positive breast cancer patients with early high-risk or locally advanced HER2 positive breast cancer. Whether nab-PHP can achieve the same effect as TCbHP is still uncertain.

Detailed Description
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In order to compare the effects of nab-PHP and TCBHP chemotherapy regimens in the neoadjuvant treatment of HER2-positive breast cancer, this study randomly divided patients who met the inclusion criteria into 2 groups through a randomized control regimen. nab-PHP regimen：Albumin binding paclitaxel 125 mg / m2 (1, 8, 15 days) + trastuzumab (8 mg / kg for the first loading dose and 6 mg / kg for the sequential maintenance dose) + patuzumab (840mg for the first loading dose and 420mg for the sequential maintenance dose) ，every 21 days for 6 cycles. TCbHP regimen：Docetaxel 75 mg/m2 + carboplatin (AUC = 6) + trastuzumab(8 mg / kg for the first loading dose and 6 mg / kg for the sequential maintenance dose) + patuzumab (840mg for the first loading dose and 420mg for the sequential maintenance dose) ，every 21 days for 6 cycles. Finally, the safety and efficacy of the two chemotherapy regimens were evaluated by postoperative PCR, ORR, DFS, OS and number of adverse events.

Official Title
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Comparing the Efficacy and Security of Nab-PHP and TCbHP in Neoadjuvant Chemotherapy for HER2 Positive Operable Breast Cancer , A Multicenter, Randomized, Phase III Clinical Trial

Conditions
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Breast Cancer,Her2 Positive

Intervention / Treatment
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* Drug: Albumin binding paclitaxel+ trastuzumab+ patuzumab
* Drug: Docetaxel+ carboplatin+ trastuzumab + patuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years ≤ age ≤ 70 years, Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1 Clinical T2-T4d, or T1c with axillary LN+ HER2 + invasive breast cancer confirmed by histopathology Note: HER2 expression positive refers to the tumor cells with immunohistochemical staining intensity of 3 + or confirmed positive by fluorescence in situ hybridization [fish] at least once during the pathological detection/review of primary tumor in the Department of pathology of participating research center hospital Clinically measurable lesions: measurable lesions revealed by ultrasound, molybdenum target or MR (optional) within 1 month before randomization Organ and bone marrow function test within one month before chemotherapy showed no chemotherapy contraindication Absolute value of neutrophil count ≥ 2.0×10^9 / L Hemoglobin ≥ 100g / L Platelet count ≥ 100×10^9 / L Total bilirubin < 1.5 ULN (upper limit of normal value) Creatinine < 1.5 × ULN AST/ALT < 1.5×ULN Echocardiography: left ventricular ejection fraction (LVEF ≥ 55%) For women of childbearing age, serum pregnancy test was negative 14 days before randomization ECOG score of 0 or 1 Signed the informed consent form prior to patient entry Exclusion Criteria: Metastatic breast cancer (Stage IV) Chemotherapy, endocrine therapy, targeted therapy and reflexotherapy have been used for this disease The patient had a second primary malignant tumor, except for the well treated skin cancer Patients who had undergone major surgery unrelated to breast cancer within 4 weeks before enrollment, or had not recovered completely from such operations Serious heart disease or discomfort, including but not limited to the following diseases: History of heart failure or systolic dysfunction (LVEF < 50%) high risk uncontrolled arrhythmias such as atrial tachycardia, resting heart rate > 100 BPM, significant ventricular arrhythmias (e.g., ventricular tachycardia) or higher-level atrioventricular block (i.e., mobitz II second degree atrioventricular block or third degree atrioventricular block) angina pectoris requiring anti angina drugs Heart valve disease with clinical significance ECG showed transmural myocardial infarction Poor control of hypertension (systolic blood pressure > 180 mmHg and / or diastolic blood pressure > 100 mmHg) Due to serious and uncontrollable other medical diseases, the researchers believe that there are chemotherapy contraindications Those who have been known to have allergic history to the drug components of this regimen; have a history of immune deficiency, including HIV positive test, or have other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Open label, randomized controlled clinical studies. 343 patients were included in each group, with a total of 686 patients enrolled.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: nab-PHP<br>Albumin binding paclitaxel + trastuzumab+ patuzumab | Drug: Albumin binding paclitaxel+ trastuzumab+ patuzumab<br>* Albumin binding paclitaxel 125 mg / m2 (1, 8, 15 days) + trastuzumab (8 mg / kg for the first loading dose and 6 mg / kg for the sequential maintenance dose) + patuzumab (840mg for the first loading dose and 420mg for the sequential maintenance dose) ，every 21 days for 6 cycles.<br>* Other names: nab-PHP regimen group;|
| Active Comparator: TCbHP<br>Docetaxel + carboplatin + trastuzumab + patuzumab | Drug: Docetaxel+ carboplatin+ trastuzumab + patuzumab<br>* Docetaxel 75 mg/m2 + carboplatin (AUC = 6) + trastuzumab(8 mg / kg for the first loading dose and 6 mg / kg for the sequential maintenance dose) + patuzumab (840mg for the first loading dose and 420mg for the sequential maintenance dose) ，every 21 days for 6 cycles.<br>* Other names: TCbHP regimen group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological Complete Response (pCR) | Percentage of Participants With Pathological Complete Response (pCR) (ypT0/is/N0M0) after 6 cycles of neoadjuvant chemotherapy | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free survival rate (EFS) | Time from randomization to any of the following events: disease progression during neoadjuvant therapy, local or remote recurrence, second primary malignant tumor (breast cancer or other cancers) or death from any cause . | 5 years after surgery | 
| Disease-free survival (DFS) | From the date of surgery to the first appearance in a local, regional, contralateral, or distant area. | 5 years after surgery | 
| number of adverse events and serious adverse events. | Evaluate the nature, incidence and severity of chemotherapy adverse events according to CTCAE 4.0 | After each cycle of chemotherapy (21 days as 1 cycle) | 
| Dose adjustment rate and withdrawal rate of chemotherapy drugs | Dose adjustment rate and withdrawal rate of chemotherapy drugs in two chemotherapy regimens | After the end of the 6th cycle of chemotherapy (21 days as 1 cycle) | 
| Exploratory endpoint - PCR rates for each subgroup and factors affecting pCR of the enrolled population | Percentage of Participants With Pathological Complete Response (pCR) | through study completion, an average of 1 year |