Multicenter, Randomized, Open-label Phase II Study to Compare the Efficacy and Safety of Trastuzumab and Paclitaxel Based Regimen Plus Carboplatin or Epirubicin as Neoadjuvant Therapy in HER2-positive Breast Cancer Patients
Overview
- Phase
- Phase 2
- Intervention
- Trastuzumab
- Conditions
- HER-2 Positive Breast Cancer
- Sponsor
- Zhimin Shao
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- pathologic complete response rate
- Last Updated
- 13 years ago
Overview
Brief Summary
The purpose of the investigators study is to compare the efficacy and safety of combining trastuzumab and paclitaxel based regimen plus carboplatin or epirubicin as neoadjuvant therapy in Chinese HER2-positive breast cancer patients. 100 patients from multicenter would be randomly assigned into two treatment arms and receive neoadjuvant chemotherapy followed by operation and adjuvant treatment. The main end point of this study would be the efficacy and safety of the two treatment arms, and the trend of the two curves is anticipated.
Detailed Description
With the increased awareness and development of the diagnosis of breast cancer, more and more breast cancer is diagnosed at early. Amplification or overexpression, or both, of human epidermal growth factor receptor-2 (HER2, also known as ERBB2), a transmembrane receptor tyrosine kinase, is present in around 22% of early breast cancers, 35% of locally advanced and metastatic tumors, and 40% of inflammatory breast cancers, and is associated with aggressive disease and poor prognosis. The significant efficacy and good safety profile of Trastuzumab targeting HER 2 combination with chemotherapy as adjuvant treatment on EBC are accepted. Currently Trastuzumab has moved to Neoadjuvant treatment combined with chemotherapy based on many publications, among them pCR is accepted as primary endpoint to evaluate the efficacy of neoadjuvant therapy. In the investigators study, Trastuzumab was concomitantly administered with different chemotherapies after randomization to determine the effect of this approach on the pathologic CR rates. 100 patients from multicenter would be randomly assigned into two treatment arms and receive neoadjuvant chemotherapy followed by operation and adjuvant treatment. Pathological complete response rate (pCR), disease free survival (DFS), response rates (RR), percentage of conserving breast surgery and adverse events including Serious AEs and non-serious AEs would be compared. The follow up time for each patients would be 3 years at most.
Investigators
Zhimin Shao
Professor and director of department of the Breast Cancer Institute, Fudan University
Fudan University
Eligibility Criteria
Inclusion Criteria
- •Female patients, presenting for the first time with invasive breast cancer, who have not received any previous treatment for an invasive malignancy
- •Aged ≥18 years and \< 70 years with life expectancy \> 12 months
- •Histologically confirmed invasive breast cancer (excluding inflammatory breast cancer) by core needle biopsy, staged II-III according to TNM Classification System, with no evidence of metastasis and tumor size ≥3 cm
- •HER2 positive confirmed by IHC 2+ and FISH positivity or IHC 3+
- •At least one measurable lesion according to RECIST criteria 1.1
- •Patients with a left ventricular ejection fraction(LVEF)≥55% by MUGA scan or echocardiography
- •ECOG PS 0-1
- •Willing to take biopsy before surgery and during chemotherapy and willing to take pre-operative chemotherapy and related treatment
- •Signed written informed consent; Able to comply with the protocol
Exclusion Criteria
- •Patient is pregnant or lactating.
- •Women of child-bearing potential must have a negative pregnancy test (urine or serum) within 7 days of drug administration and agree to take an adequate contraceptive measure
- •Previous treatment with chemotherapy or hormonal therapy or any prior therapy with an anti-HER2 therapy for any malignancy.
- •History of congestive heart failure, uncontrolled or symptomatic angina pectoris, arrhythmia or myocardial infarction
- •Other invasive malignancy (including second primary breast cancer) which could affect compliance with the protocol or interpretation of results. Patients who have been curatively treated and free of malignant disease for greater than 5 years are generally eligible
- •Inadequate bone marrow, hepatic and renal functions as evidenced by the following:
- •Neutrophil count of \<1500/uL,
- •Platelet count of \<100,000/uL.
- •Haemoglobin \<10 g/dL.
- •Serum total bilirubin \> 1.5\*ULN (upper limit of normal),
Arms & Interventions
Trastuzumab+ Carboplatin+Paclitaxel
Neoadjuvant treatment regimen:Trastuzumab,Carboplatin,Paclitaxel
Intervention: Trastuzumab
Trastuzumab+ Carboplatin+Paclitaxel
Neoadjuvant treatment regimen:Trastuzumab,Carboplatin,Paclitaxel
Intervention: Paclitaxel
Trastuzumab+ Carboplatin+Paclitaxel
Neoadjuvant treatment regimen:Trastuzumab,Carboplatin,Paclitaxel
Intervention: Carboplatin
Trastuzumab+Epirubicin+Paclitaxel
Neoadjuvant treatment regimen:Trastuzumab,Epirubicin,Paclitaxel
Intervention: Trastuzumab
Trastuzumab+Epirubicin+Paclitaxel
Neoadjuvant treatment regimen:Trastuzumab,Epirubicin,Paclitaxel
Intervention: Paclitaxel
Trastuzumab+Epirubicin+Paclitaxel
Neoadjuvant treatment regimen:Trastuzumab,Epirubicin,Paclitaxel
Intervention: Epirubicin
Outcomes
Primary Outcomes
pathologic complete response rate
Time Frame: 3 years
Percentage of complete pathological response, e.g. no microscopic evidence of residual invasive tumor cells in any resected specimens of the breast and/or axillary nodes.
Secondary Outcomes
- Disease free survival(3 years at most)
- Overall response rate(3 years)
- Percentage of conserving breast surgery(3 years)
- Safety(3 years)