Trastuzumab Plus Taxane Neoadjuvant Therapy for HER2-Positive Breast Carcinoma: A Phase II Study

Phase 2

Not yet recruiting

• Conditions: Breast Carcinoma in Situ
• Interventions: Drug: Trastuzumab combined with taxane neoadjuvant therapy

• Registration Number: NCT06843681
• Lead Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Brief Summary

This is a phase II single-center single-arm clinical study designed to analyze the efficacy and safety of trastuzumab combined with taxane neoadjuvant therapy for HER2-positive breast carcinoma in situ (or with invasive carcinoma).

Detailed Description

This Phase II single-center, single-arm clinical study was designed to evaluate the efficacy and safety of trastuzumab combined with taxane as a neoadjuvant treatment for patients with HER2-positive breast cancer in situ or invasive breast cancer. The study was designed to determine breast-conserving surgery rates and pathologic complete response (pCR) rates, assess tumor size reduction, and evaluate potential adverse events associated with treatment options. Participants will be treated with trastuzumab and taxane on a prescribed schedule, with periodic evaluations including imaging, histopathological analysis, and safety monitoring. The aim is to gain insight into the therapeutic potential of this combination therapy in improving outcomes for patients with HER2-positive breast cancer.

Study Timeline

• Study First Submitted: 2024-12-26
• Status Verified: 2025-02
• Study First Submitted QC: 2025-02-24
• Last Update Submitted: 2025-02-24
• Study First Posted: 2025-02-25
• Last Update Posted: 2025-02-25
• Study Start: 2025-03-01
• Primary Completion: 2027-01-01
• Study Completion: 2030-01-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 54

Inclusion Criteria

1. Diagnosed breast carcinoma in situ (female, 18 to 70 years old);

2. Breast mass ≥2cm, and in situ cancer pathology confirmed HER2 positive (definition: immunohistochemical results 3+ or in situ hybridization results positive);

3. No evidence of distant transfer;

4. Have not received any previous cancer treatment;

5. Imaging examination showed at least one measurable lesion within 2 weeks before enrollment;

6. Left ventricular ejection fraction (LVEF) was measured by echocardiography ≥50%;

7. Previous treatment-related toxicity should be alleviated to NCI CTCAE (version 5.0) ≤1 degree, AST and ALT≤2.5 times the upper limit of normal, total bilirubin ≤1.5 times the upper limit of normal;

8. Liver and kidney function tests are basically normal:

   1. Total bilirubin (TBIL) ≤3× upper limit of normal (ULN),
   2. Alanine aminotransferase and aspartate aminotransferase (ALT/AST) ≤2.5×ULN (patients with liver metastasis ≤5xULN),
   3. Serum creatinine ≤1.5×ULN or creatinine clearance (Ccr) ≥60 ml/min;

9. Adequate bone marrow functional reserve:

   1. White blood cell count (WBC) ≥3.0×10^9 / L,
   2. Neutrophil count (ANC) ≥1.5×10^9 / L,
   3. Platelet count (PLT) ≥70×10^9 / L

10. Fertile women must use contraceptives;

11. Be able to understand the research process, voluntarily participate in the study, and sign the informed consent.

Exclusion Criteria

1. Metastatic breast cancer (stage IV);
2. History of invasive breast cancer, or prior systemic treatment to treat or prevent breast cancer;
3. Previous or concurrent malignant diseases, except skin basal cell carcinoma or cervical cancer in situ;
4. Patients with severe heart disease or discomfort that is not expected to tolerate chemotherapy, including but not limited to: fatal arrhythmias or higher grade atrioventricular block, unstable angina pectoris, clinically significant valvular disease, transmural myocardial infarction shown by electrocardiogram, uncontrolled hypertension;
5. Insufficient bone marrow or kidney function, liver function impairment;
6. Grade 2 or more severe peripheral neuropathy;
7. Patients with thrombocytopenia, neutropenia, anemia, hypokalemia, and elevation of alanine aminotransferase or aspartate aminotransferase above CTCAE Level 1;
8. Patients who are known to be allergic to the active ingredient or other ingredient of the investigational drug;
9. Had received radiotherapy, chemotherapy, endocrine therapy, or was participating in any interventional drug clinical trial within 4 weeks prior to enrollment;
10. Pregnant or lactating women, women of childbearing age who refused to use effective contraception during the study period;
11. Any other conditions that the investigator considers the patient unfit to participate in the study, concomitant diseases or conditions that may interfere with study participation, or any serious medical disorder that may affect the safety of the subject (e.g., uncontrolled heart disease, high blood pressure, active or uncontrollable infection, active hepatitis B virus infection).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
treatment	Trastuzumab combined with taxane neoadjuvant therapy	The study includes a single treatment arm where all participants will receive a combination of trastuzumab and taxane as part of the neoadjuvant therapy. This treatment arm is designed to assess the efficacy and safety of the regimen in patients with HER2-positive breast carcinoma in situ 1. Trastuzumab (HER2-Targeted Therapy): * Trastuzumab will be administered intravenously at a standard dosage based on the patient's body weight. The initial dose will be a loading dose followed by maintenance doses every three weeks, as per clinical guidelines for HER2-positive breast cancer treatment. * The therapy targets the HER2 receptor to inhibit tumor growth and improve response rates. 2. Taxane (Chemotherapy): * A taxane-based chemotherapeutic agent (e.g., paclitaxel or docetaxel) will be administered intravenously. The specific agent, dosage, and schedule will follow standard protocols used in the neoadjuvant setting for HER2-positive breast cancer. * Taxanes work by disrupting microt

Primary Outcome Measures

Name	Time	Method
Breast-conserving surgery rate after 4-6 cycles of treatment	From the start of neoadjuvant therapy to the completion of surgery (approximately 3-4 months after enrollment)	The breast-conserving surgery rate was calculated as a percentage of the total number of patients who successfully completed breast-conserving surgery after neoadjuvant therapy. For this study, all patients were required to confirm after treatment that the tumor was resectable and had no significant metastasis by imaging evaluation, such as breast ultrasound or MRI.

Secondary Outcome Measures

Name	Time	Method
pathological Complete Response (pCR)	Within 3-4 months from enrollment, at the completion of neoadjuvant therapy.	pCR refers to the situation in which a patient's carcinoma in situ tumor has completely disappeared through pathological examination after neoadjuvant therapy.; Measurement Tool: Histopathological examination of surgical specimens.
Objective Response Rate (ORR)	Within 3-4 months from enrollment, at the completion of neoadjuvant therapy.	ORR is the proportion of patients whose tumors have shrunk significantly over the course of treatment. Specifically, ORR includes both partial response (PR) and complete response (CR). Partial response (PR) : The maximum diameter or volume of the tumor is reduced by at least 30%, but it does not completely disappear. Complete response (CR) : The tumor disappears completely and no visible signs of cancer are confirmed by imaging tests, such as CT scans, MRI, or ultrasound.; Measurement Tool: Imaging assessments (MRI, CT, or ultrasound).
Disease-free survival of 3 years	At 36 months from the date of enrollment.	Disease-free survival (DFS) is the time from the start of treatment until the disease returns, progresses, or dies. In this study, 3-year disease-free survival was defined as patients who did not experience tumor recurrence or metastasis during a follow-up period of at least 3 years after treatment.; Measurement Tool: Clinical and imaging follow-ups, verified by medical records.
Disease-free survival of 5 years	At 60 months from the date of enrollment.	Measurement Tool: Clinical and imaging follow-ups, verified by medical records.
Overall survival	From enrollment to 60 months ± 3 months or until the date of death from any cause, whichever occurs first.	Measurement Tool: Survival status verified through medical records and patient follow-up.
Biomarker analysis o f HER2 and Ki-67 using immunohistochemistry (IHC) or quantitative PCR	Within 4-6 months from enrollment, at the completion of surgery.	Measurement Tool: Expression levels of specific biomarkers, such as HER2 and Ki-67, will be assessed using immunohistochemistry (IHC) or quantitative PCR, with tumor tissue or blood samples collected at baseline and post-therapy.
AE rate	From enrollment to 12 months after the end of study treatment.	Adverse event rate
Assessment of quality of life in patients using the FACT-B scale	From enrollment to 12 months after the end of study treatment or the last follow-up visit.	Quality of life refers to people's perception and experience of their physical state, mental function, social ability, and overall personal situation based on socioeconomic, cultural background and value orientation. FACT-B scale was used to assess patients before treatment, during treatment (from the first day of the third cycle, and every two cycles thereafter), and 30 days after treatment. Patients' quality of life was quantified by the proportion of changes in the score