Efficacy and Safety Study of Trastuzumab and Paclitaxel Based Regimens to Treat HER2-positive Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01428414
Recruitment Status : Unknown
Verified August 2012 by Zhimin Shao, Fudan University.
Recruitment status was:  Active, not recruiting
First Posted : September 5, 2011
Last Update Posted : August 23, 2012
Roche Pharma AG
Information provided by (Responsible Party):
Zhimin Shao, Fudan University

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.

Condition or disease Intervention/treatment Phase
HER-2 Positive Breast Cancer Drug: Trastuzumab Drug: Paclitaxel Drug: Epirubicin Drug: Carboplatin Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : August 2011
Estimated Primary Completion Date : August 2014
Estimated Study Completion Date : February 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Trastuzumab+ Carboplatin+Paclitaxel
Neoadjuvant treatment regimen:Trastuzumab,Carboplatin,Paclitaxel
Drug: Trastuzumab
2 mg/kg, iv, d1,8,15(loading dose 4mg/kg wk1), qw
Other Name: Herceptin
Drug: Paclitaxel
75mg/m2, iv d1, 8,15. qw; 4-6 cycles
Other Name: Taxol
Drug: Carboplatin
AUC 2, qw, iv d1, 8,15. 4-6 cycles
Active Comparator: Trastuzumab+Epirubicin+Paclitaxel
Neoadjuvant treatment regimen:Trastuzumab,Epirubicin,Paclitaxel
Drug: Trastuzumab
2 mg/kg, iv, d1,8,15(loading dose 4mg/kg wk1), qw
Other Name: Herceptin
Drug: Paclitaxel
75mg/m2, iv d1, 8,15. qw; 4-6 cycles
Other Name: Taxol
Drug: Epirubicin
75mg/m2, iv d1, q3w, 4-6 cycles
Other Name: Epirubicin Hydrochloride for Injection

Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Disease free survival [ Time Frame: 3 years at most ]
    Percentage of recurrence-free survival using Kaplan-Meier method, including subgroup analysis of DFS who complete 1-year trastuzumab treatment

  2. Overall response rate [ Time Frame: 3 years ]
    Percentage of clinical objective response using the RECIST scale

  3. Percentage of conserving breast surgery [ Time Frame: 3 years ]
    Percentage of conserving breast surgery

  4. Safety [ Time Frame: 3 years ]
    Incidence and severity of adverse events using the NCI-CTC scale 4.0

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Ages Eligible for Study:   18 Years to 69 Years   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Female patients, presenting for the first time with invasive breast cancer, who have not received any previous treatment for an invasive malignancy
  2. Aged ≥18 years and < 70 years with life expectancy > 12 months
  3. 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
  4. HER2 positive confirmed by IHC 2+ and FISH positivity or IHC 3+
  5. At least one measurable lesion according to RECIST criteria 1.1
  6. Patients with a left ventricular ejection fraction(LVEF)≥55% by MUGA scan or echocardiography
  7. ECOG PS 0-1
  8. Willing to take biopsy before surgery and during chemotherapy and willing to take pre-operative chemotherapy and related treatment
  9. Signed written informed consent; Able to comply with the protocol

Exclusion Criteria:

  1. Patient is pregnant or lactating.
  2. 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
  3. Previous treatment with chemotherapy or hormonal therapy or any prior therapy with an anti-HER2 therapy for any malignancy.
  4. History of congestive heart failure, uncontrolled or symptomatic angina pectoris, arrhythmia or myocardial infarction
  5. 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
  6. 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),
    • ALT or AST > 2.5*ULN,
    • Alkaline phosphatase > 2.5*ULN,
    • Serum creatinine > 1.5*ULN.
  7. Other serious illness or medical condition including:

    • Congestive heart failure (NYHA class II, III, IV) or history of documented congestive heart failure, unstable angina pectoris, myocardial infarction in the last 6 months, clinically significant valvular heart disease, or high-risk uncontrolled arrhythmias.
    • Patients with dyspnoea at rest due to malignant or other disease (e.g. pulmonary metastases with lymphangitis) or who require supportive oxygen therapy.
    • Active serious uncontrolled infections.
    • Poorly controlled diabetes mellitus.
  8. Not willing to take pre-operative biopsy or neo-adjuvant therapy
  9. Patients with psychiatric disorder or other disease leading to incompliance to the therapy
  10. Known hypersensitivity to any ingredient of the regimen
  11. Treatment with any investigational drug within 30 days before the beginning of treatment with study drug.

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01428414

China, Shanghai
Breast cancer institute of Fudan University Cancer Hospital
Shanghai, Shanghai, China, 200032
Sponsors and Collaborators
Zhimin Shao
Roche Pharma AG
Principal Investigator: Zhi-Ming Shao, MD Fudan University


Responsible Party: Zhimin Shao, Professor and director of department of the Breast Cancer Institute, Fudan University, Fudan University Identifier: NCT01428414     History of Changes
Other Study ID Numbers: ML27770
First Posted: September 5, 2011    Key Record Dates
Last Update Posted: August 23, 2012
Last Verified: August 2012

Keywords provided by Zhimin Shao, Fudan University:
Breast cancer
neoadjuvant chemotherapy

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors