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

Phase 3

Recruiting

• Conditions: Breast Cancer,HER2-positive
• Interventions: Drug: Docetaxel+ carboplatin+ trastuzumab + patuzumab; Drug: Nab-paclitaxel+ trastuzumab+ patuzumab

• Registration Number: NCT04547907
• Lead Sponsor: Henan Cancer Hospital

Brief Summary

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

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 Timeline

• Study First Submitted: 2020-08-29
• Study First Submitted QC: 2020-09-08
• Study First Posted: 2020-09-14
• Study Start: 2020-09-18
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-12
• Last Update Posted: 2024-04-15
• Primary Completion: 2024-12-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 688

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TCbHP	Docetaxel+ carboplatin+ trastuzumab + patuzumab	Docetaxel + carboplatin + trastuzumab + patuzumab
nab-PHP	Nab-paclitaxel+ trastuzumab+ patuzumab	Nab-paclitaxel + trastuzumab+ patuzumab

Primary Outcome Measures

Name	Time	Method
Pathological Complete Response (pCR)	through study completion, an average of 1 year	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).

Secondary Outcome Measures

Name	Time	Method
Event-Free Survival (EFS)	5 years after surgery	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.
Invasive Disease-Free Survival (iDFS)	5 years after surgery	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.
Safety-Number of adverse events and serious adverse events.	After each cycle of chemotherapy (21 days as 1 cycle)	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).
Tolerability-Dose adjustment rate and withdrawal rate of chemotherapy drugs	After the end of the 6th cycle of chemotherapy (21 days as 1 cycle)	Tolerability will be assessed by evaluating the dose adjustment rate and discontinuation rate of chemotherapy drugs in both treatment regimens.
Exploratory endpoint - Differences in pCR rates between predefined subgroups and factors influencing pCR in the study population.	through study completion, an average of 1 year	The differences in pCR rate between various predefined subgroups and the factors affecting pCR in the enrolled population will be explored.

Trial Locations

Locations (1)

Henan cancer hospital; 🇨🇳 Zhengzhou, Henan, China