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

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)

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: nab-paclitaxel; Drug: trastuzumab; Drug: Doxorubicin; Drug: cyclophosphamide; Biological: Growth Factor Support; Procedure: Surgery

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
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Hays, Kansas, United States, 67601
      • Hays Medical Center
    • Kansas City, Kansas, United States, 66205
      • University of Kansas Medical Center Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: Abraxane; Drug: trastuzumab; 4 MG loading dose followed by 2 MG/KG every week for a total of 12 weeks; Other Names: Herceptin; Drug: Doxorubicin; 60 MG/M2 every two weeks for a total of 4 cycles; Other Names: Adriamycin; Drug: cyclophosphamide; 600 MG/M2 every 2 weeks for 4 cycles (administered with Doxorubicin above); Other Names: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pathologic Complete Response	22 weeks

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Collaborators: Celgene Corporation
• Investigators: Principal Investigator: Qamar Khan, MD, University of Kansas Medical Center Cancer Center

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): August 1, 2017

Study Registration Dates

• First Submitted: July 16, 2009
• First Submitted That Met QC Criteria: July 21, 2009
• First Posted (Estimate): July 22, 2009

Study Record Updates

• Last Update Posted (Actual): April 23, 2018
• Last Update Submitted That Met QC Criteria: March 21, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: HER2; Trastuzumab; Nab-paclitaxel; invasive breast cancer; primary breast cancer; neo-adjuvant therapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Cyclophosphamide; Paclitaxel; Trastuzumab; Doxorubicin; Mitogens
• Other Study ID Numbers: 11368