A Comparison of Nab-PHP and TCbHP Efficacy in Neoadjuvant Therapy for HER2-positive Early Breast Cancer

Comparing the Efficacy of Nab-PHP and TCbHP in Neoadjuvant Therapy for HER2-positive Early Breast Cancer, A Multicenter, Randomized, Phase III Clinical Trial

The aim of this study is to evaluates the efficacy of weekly nab-paclitaxel monotherapy compared to the standard regimen of docetaxel plus carboplatin, both supplemented with trastuzumab and pertuzumab, as neoadjuvant therapies for HER2-positive breast cancer.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer,HER2-positive
• Intervention / Treatment: Drug: Nab-paclitaxel+ trastuzumab+ patuzumab; Drug: Docetaxel+ carboplatin+ trastuzumab + patuzumab

Detailed Description

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： the neoadjuvant chemotherapy with 6*nab-PHP regimen group (experimental group): nab-paclitaxel 125mg/m2 on days 1, 8, and 15 every 21 days as one cycle; 6*TCbHP regimen (control group): docetaxel 75 mg/m2 + carboplatin (AUC=6) on day 1. Both groups will receive trastuzumab (loading dose 8 mg/kg followed by a maintenance dose of 6 mg/kg) on day 1 and pertuzumab (loading dose 840 mg followed by a maintenance dose of 420 mg) on day 1, every 21 days as one cycle.

Surgery will be performed after completion of neoadjuvant chemotherapy, with intraoperative excision of specimens (breast + axilla) for pathological evaluation.

Comparative analysis of pCR, EFS, iDFS and safety outcomes between the two groups will be conducted using appropriate statistical methods.

Safety evaluation will include the incidence of adverse events, incidence of serious adverse events, dose adjustment rate, and discontinuation rate.

• Study Type: Interventional
• Enrollment (Estimated): 688
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Zhenzhen Liu; Phone Number: 13603862755; Email: liuzhenzhen73@163.com
• Study Contact Backup: Name: Jiujun Zhu; Phone Number: 13676962766; Email: bigapple0601@126.com

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China
      • Recruiting
      • Henan Cancer Hospital
      • Contact: Zhenzhen Liu; Phone Number: 17729798130; Email: liuzhenzhen73@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age: 18-70 years;
2. Clinical T2-T4d, or T1c with axillary lymph node positivity;
3. Histopathologically confirmed HER2-positive invasive breast cancer; Note: HER2 positivity was determined by immunohistochemical (IHC) staining of 3+ or, if IHC 2+, by HER2 gene amplification as demonstrated by fluorescence in situ hybridization (FISH) assay；
4. Have clinically measurable lesions: Measurable lesions shown on ultrasound, mammography, or MR (optional) within 1 month before randomization;

5. No chemotherapy contraindications detected by organ and bone marrow function tests within 1 month before chemotherapy:

   1. Neutrophil count absolute value ≧2.0×109/L;
   2. Hemoglobin ≧ 100g/L;
   3. Platelet count ≧100×109/L;
   4. Total bilirubin <1.5 ULN (upper limit of normal);
   5. Creatinine < 1.5×ULN
   6. AST/ALT < 1.5×ULN;
6. Cardiac ultrasound: Left ventricular ejection fraction (LVEF ≥ 55%);
7. Reproductive age women, negative serum pregnancy test within 14 days before randomization;
8. ECOG score 0 or 1;
9. Signature of informed consent.

Exclusion Criteria:

1. Stage IV (metastatic) breast cancer;
2. Bilateral breast cancer;
3. Patients who have received chemotherapy, endocrine therapy, targeted therapy, or radiotherapy for this disease;
4. Patients with a second primary malignancy, except for adequately treated skin cancer;
5. Major non-breast cancer-related surgical procedures within the past 4 weeks before enrollment, or patients have not fully recovered from such surgical procedures;

6. Severe heart disease or conditions that do not allow participation in the study, including but not limited to the following:

   1. History of heart failure or systolic dysfunction (LVEF < 50%);
   2. High-risk uncontrolled arrhythmias, such as atrial tachycardia, resting heart rate > 100 bpm, significant ventricular arrhythmias (such as ventricular tachycardia) or higher-grade atrioventricular conduction blocks (i.e., Mobitz II second-degree atrioventricular block or third-degree atrioventricular block);
   3. Angina pectoris requiring anti-anginal drug therapy;
   4. Clinically significant valvular heart disease;
   5. ECG showing a transmural myocardial infarction;
   6. Uncontrolled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg);
7. Due to severe and uncontrolled other medical conditions, the investigator considers chemotherapy to be contraindicated;
8. Known history of allergy to any component of the study drugs; patients with a history of immune deficiency diseases, including HIV positivity, or patients with other acquired or congenital immune deficiency diseases, or a history of organ transplantation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: TCbHP; Docetaxel + carboplatin + trastuzumab + patuzumab	Drug: Docetaxel+ carboplatin+ trastuzumab + patuzumab; Docetaxel 75 mg/m2(day 1) + Carboplatin (AUC=6) (day 1) + Trastuzumab (initial loading dose of 8 mg/kg, subsequent maintenance dose of 6 mg/kg) + Pertuzumab (initial loading dose of 840mg, subsequent maintenance dose of 420mg), every 21 days constitute a cycle.; Other Names: TCbHP regimen group
Experimental: nab-PHP; Nab-paclitaxel + trastuzumab+ patuzumab	Drug: Nab-paclitaxel+ trastuzumab+ patuzumab; Nab-paclitaxel 125mg/m2 (days 1, 8, 15) + Trastuzumab (initial loading dose of 8 mg/kg, subsequent maintenance dose of 6 mg/kg) + Pertuzumab (initial loading dose of 840mg, subsequent maintenance dose of 420mg), every 21 days constitute a cycle.; Other Names: nab-PHP regimen group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Complete Response (pCR)	Pathological Complete Response (pCR) rate: 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).	through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-Free Survival (EFS)	EFS is defined as the time from randomization to any of the following events: disease progression during neoadjuvant treatment, disease recurrence, or any cause of death.	5 years after surgery
Invasive Disease-Free Survival (iDFS)	This refers to the time from surgery to the first documented occurrence of an event such as ipsilateral invasive breast tumour recurrence, distant recurrence, contralateral invasive breast cancer, or death from any cause.	5 years after surgery
Safety-Number of adverse events and serious adverse events.	Safety will be assessed by evaluating the nature, incidence, and severity of chemotherapy-related adverse events according to CTCAE 4.0 (Common Terminology Criteria for Adverse Events).	After each cycle of chemotherapy (21 days as 1 cycle)
Tolerability-Dose adjustment rate and withdrawal rate of chemotherapy drugs	Tolerability will be assessed by evaluating the dose adjustment rate and discontinuation rate of chemotherapy drugs in both treatment regimens.	After the end of the 6th cycle of chemotherapy (21 days as 1 cycle)
Exploratory endpoint - Differences in pCR rates between predefined subgroups and factors influencing pCR in the study population.	The differences in pCR rate between various predefined subgroups and the factors affecting pCR in the enrolled population will be explored.	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Henan Cancer Hospital
• Investigators: Principal Investigator: Zhenzhen Liu, Study Principal Investigator Henan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2020
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: August 29, 2020
• First Submitted That Met QC Criteria: September 8, 2020
• First Posted (Actual): September 14, 2020

Study Record Updates

• Last Update Posted (Actual): September 20, 2024
• Last Update Submitted That Met QC Criteria: September 18, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Docetaxel; Carboplatin; Paclitaxel; Trastuzumab
• Other Study ID Numbers: HELEN-006

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No