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Evaluate Trastuzumab Plus Standard Chemotherapy Given Before Surgery in Breast Cancer Patients With Low HER 2 Expression

Phase 2
Completed
Conditions
Breast Cancer
Interventions
Biological: Growth Factor Support
Procedure: Surgery
Registration Number
NCT00944047
Lead Sponsor
University of Kansas Medical Center
Brief Summary

The purpose of this study is to find out if there is a benefit of adding Herceptin (trastuzumab) to standard chemotherapy in this type of breast cancer.

Detailed Description

Neoadjuvant (primary) chemotherapy refers to chemotherapy given before surgery. Neoadjuvant chemotherapy has a number of potential advantages including increasing the chances for breast preservation at the time of surgery as well as it may improve the local control of the cancer. Several national breast cancer studies have shown that neoadjuvant chemotherapy was equal to chemotherapy given following surgery.

A standard treatment for stage II or Stage III invasive breast cancer with low HER2 expression is combination chemotherapyAdriamycin, Cytoxan,followed by a Taxane: given either before or after surgery), followed by surgery +/- radiation therapy.

The main purpose of chemotherapy however is to reduce the risk of recurrence of cancer and also make surgery more successful. HER2 is a receptor located on the surface of some cells. This receptor plays a role in regulating the growth of the cell, in addition to the growth of tumors. High levels of the HER2 receptor may predict those women who benefit from treatment with agents such as Herceptin that target HER2. Herceptin (Trastuzumab) is a drug that is effective both alone and in combination with standard chemotherapy. There is some data to suggest that patients whose tumors have low expression of the HER2 protein and are normal by FISH may also receive benefit from Herceptin.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
32
Inclusion Criteria
  • Female patient ≥ 18 years of age
  • Histologically proven stage II or III adenocarcinoma of the breast
  • Must be candidate for neoadjuvant treatment (Tumor size ≥ 2 cm, T2, T3, T4 and/or clinical N1 or N2).
  • HER-2/neu 1+ or 2+ by immunohistochemistry
  • Must have operable tumor.
  • Performance status of 2 or better per SWOG criteria
  • LVEF ≥ 55% by echocardiogram performed within 4 weeks prior to treatment initiation
  • If patient of childbearing potential, pregnancy test is negative
  • Patients with reproductive potential must use an effective method to avoid pregnancy for the duration of the trial.
  • Adequate bone marrow function: ANC > 1500/mm3, platelet count > 100,000/mm3, and hemoglobin > 9 g/dL
  • Adequate kidney function: serum creatinine of < 1.5mg/dl and/or creatinine clearance of > 60 mL/min
  • Adequate hepatic function: transaminases < 2.5 x upper limit of normal and total bilirubin < 1.5 mg/dL
  • Must be informed of the investigational nature of the study and must sign an informed consent in accordance with the institutional rules.
  • Pretreatment lab values must be performed within 14 days of patient registration, and other baseline studies (with the exception of mammogram) must be performed within 30 days of patient registration.

EXCLUSION CRITERIA:

  • Patient with metastatic breast cancer.
  • Women with tumors that are HER-2 neu 0+ or 3+ by immunohistochemistry
  • Women with HER 2 FISH amplified tumors (FISH ratio >2.2)
  • Patients who have had prior endocrine therapy for > 4 weeks or chemotherapy for this breast cancer will be excluded.
  • Locally advanced, inoperable tumors will be excluded.
  • The presence of any other medical or psychiatric disorder that, in the opinion of the treating physician, would contraindicate the use of drugs in this protocol or place the subject at undue risk for treatment complications.
  • History of significant cardiac disease, cardiac risk factors or uncontrolled arrhythmias
  • Ejection fraction < 55%
  • Pregnancy or lactation
  • Patients with inadequate laboratory values (as defined above) are excluded from study.
  • Patients with NCI common toxicity criteria (CTC) grade 2 or greater peripheral neuropathy are excluded from study.
  • Patients with active infection are excluded from study.
  • Patients with concomitant or previous malignancies within the last 5 years, are excluded from the study. Exceptions include: adequately treated basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, and ductal carcinoma in situ (DCIS).
  • Patients with emotional limitations are excluded from study.
Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Intervention Armnab-paclitaxelNab-paclitaxel, trastuzumab, doxorubicin, cyclophosphamide, Growth Factor Support, Surgery
Intervention ArmGrowth Factor SupportNab-paclitaxel, trastuzumab, doxorubicin, cyclophosphamide, Growth Factor Support, Surgery
Intervention ArmSurgeryNab-paclitaxel, trastuzumab, doxorubicin, cyclophosphamide, Growth Factor Support, Surgery
Intervention ArmtrastuzumabNab-paclitaxel, trastuzumab, doxorubicin, cyclophosphamide, Growth Factor Support, Surgery
Intervention ArmDoxorubicinNab-paclitaxel, trastuzumab, doxorubicin, cyclophosphamide, Growth Factor Support, Surgery
Intervention ArmcyclophosphamideNab-paclitaxel, trastuzumab, doxorubicin, cyclophosphamide, Growth Factor Support, Surgery
Primary Outcome Measures
NameTimeMethod
Pathologic Complete Response22 weeks
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (2)

University of Kansas Medical Center Cancer Center

🇺🇸

Kansas City, Kansas, United States

Hays Medical Center

🇺🇸

Hays, Kansas, United States

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