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

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: NCT00944047
Recruitment Status : Completed
First Posted : July 22, 2009
Results First Posted : April 23, 2018
Last Update Posted : April 23, 2018
Celgene Corporation
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: nab-paclitaxel Drug: trastuzumab Drug: Doxorubicin Drug: cyclophosphamide Biological: Growth Factor Support Procedure: Surgery Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Abraxane and Trastuzumab Followed by Dose Dense Doxorubicin and Cyclophosphamide as Neoadjuvant Therapy in Invasive Breast Cancer With Low HER2 Expression (1+ or 2+ by IHC)
Study Start Date : July 2009
Actual Primary Completion Date : May 2014
Actual Study Completion Date : August 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Trastuzumab

Arm Intervention/treatment
Experimental: Intervention Arm
Nab-paclitaxel, trastuzumab, doxorubicin, cyclophosphamide, Growth Factor Support, Surgery
Drug: nab-paclitaxel
100 MG/M2 IV over 30 minutes once a week for 12 weeks
Other Name: Abraxane

Drug: trastuzumab
4 MG loading dose followed by 2 MG/KG every week for a total of 12 weeks
Other Name: Herceptin

Drug: Doxorubicin
60 MG/M2 every two weeks for a total of 4 cycles
Other Name: Adriamycin

Drug: cyclophosphamide
600 MG/M2 every 2 weeks for 4 cycles (administered with Doxorubicin above)
Other Name: Cytoxan

Biological: Growth Factor Support
  • All patients will receive pegfilgrastim 6.0 mg sc on Day #2 of each doxorubicin/cyclophosphamide neoadjuvant treatment cycle.
  • Erythropoetic growth factor support for fatigue/anemia will be allowed at the discretion of the treating physician.

Procedure: Surgery
  • After completion of neoadjuvant therapy, patients will proceed with either modified radical mastectomy or lumpectomy.
  • All patients with pretreatment lymph node positive disease and positive sentinel lymph node will undergo complete axillary lymph node dissection.

Primary Outcome Measures :
  1. Pathologic Complete Response [ Time Frame: 22 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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.


  • 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.

Information from the National Library of Medicine

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): NCT00944047

United States, Kansas
Hays Medical Center
Hays, Kansas, United States, 67601
University of Kansas Medical Center Cancer Center
Kansas City, Kansas, United States, 66205
Sponsors and Collaborators
University of Kansas Medical Center
Celgene Corporation
Principal Investigator: Qamar Khan, MD University of Kansas Medical Center Cancer Center

Responsible Party: University of Kansas Medical Center Identifier: NCT00944047     History of Changes
Other Study ID Numbers: 11368
First Posted: July 22, 2009    Key Record Dates
Results First Posted: April 23, 2018
Last Update Posted: April 23, 2018
Last Verified: March 2018

Keywords provided by University of Kansas Medical Center:
invasive breast cancer
primary breast cancer
neo-adjuvant therapy

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Liposomal doxorubicin
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors