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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer,Her2 Positive
• Intervention / Treatment: Drug: Albumin binding 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.

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.

• 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. 18 years ≤ age ≤ 70 years, Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1
2. Clinical T2-T4d, or T1c with axillary LN+
3. 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
4. Clinically measurable lesions: measurable lesions revealed by ultrasound, molybdenum target or MR (optional) within 1 month before randomization

5. 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
6. Echocardiography: left ventricular ejection fraction (LVEF ≥ 55%)
7. For women of childbearing age, serum pregnancy test was negative 14 days before randomization
8. ECOG score of 0 or 1
9. Signed the informed consent form prior to patient entry

Exclusion Criteria:

1. Metastatic breast cancer (Stage IV)
2. Chemotherapy, endocrine therapy, targeted therapy and reflexotherapy have been used for this disease
3. The patient had a second primary malignant tumor, except for the well treated skin cancer
4. Patients who had undergone major surgery unrelated to breast cancer within 4 weeks before enrollment, or had not recovered completely from such operations

5. 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)
6. Due to serious and uncontrollable other medical diseases, the researchers believe that there are chemotherapy contraindications
7. 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;

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
Experimental: nab-PHP; Albumin binding paclitaxel + trastuzumab+ patuzumab	Drug: Albumin binding paclitaxel+ trastuzumab+ patuzumab; 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.; Other Names: nab-PHP regimen group
Active Comparator: TCbHP; Docetaxel + carboplatin + trastuzumab + patuzumab	Drug: Docetaxel+ carboplatin+ trastuzumab + patuzumab; 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.; Other Names: TCbHP regimen group

What is the study measuring?

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

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 (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 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