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

August 21, 2012 updated by: Zhimin Shao

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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

Enrollment (Anticipated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200032
        • Breast cancer institute of Fudan University Cancer Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 69 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / 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 Names:
  • Herceptin
Drug: Paclitaxel
75mg/m2, iv d1, 8,15. qw; 4-6 cycles
Other Names:
  • Taxol
Drug: Carboplatin
AUC 2, qw, iv d1, 8,15. 4-6 cycles
Other Names:
  • CARBOPLATIN FOR INJECTION
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 Names:
  • Herceptin
Drug: Paclitaxel
75mg/m2, iv d1, 8,15. qw; 4-6 cycles
Other Names:
  • Taxol
Drug: Epirubicin
75mg/m2, iv d1, q3w, 4-6 cycles
Other Names:
  • Epirubicin Hydrochloride for Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
3 years at most
Overall response rate
Time Frame: 3 years
Percentage of clinical objective response using the RECIST scale
3 years
Percentage of conserving breast surgery
Time Frame: 3 years
Percentage of conserving breast surgery
3 years
Safety
Time Frame: 3 years
Incidence and severity of adverse events using the NCI-CTC scale 4.0
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Zhimin Shao

Collaborators

Roche Pharma AG

Investigators

  • Principal Investigator: Zhi-Ming Shao, MD, Fudan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2011

Primary Completion (ANTICIPATED)

August 1, 2014

Study Completion (ANTICIPATED)

February 1, 2015

Study Registration Dates

First Submitted

August 28, 2011

First Submitted That Met QC Criteria

September 2, 2011

First Posted (ESTIMATE)

September 5, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

August 23, 2012

Last Update Submitted That Met QC Criteria

August 21, 2012

Last Verified

August 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ML27770

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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