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

Breast Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00944047
• Other study ID #: 11368
• Status: Completed
• Phase: Phase 2
• First received: July 16, 2009
• Last updated: March 21, 2018
• Start date: July 2009
• Est. completion date: August 2017

Study information

• Verified date: March 2018
• Source: University of Kansas Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: August 2017
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• nab-paclitaxel
100 MG/M2 IV over 30 minutes once a week for 12 weeks
• trastuzumab
4 MG loading dose followed by 2 MG/KG every week for a total of 12 weeks
• Doxorubicin
60 MG/M2 every two weeks for a total of 4 cycles
• cyclophosphamide
600 MG/M2 every 2 weeks for 4 cycles (administered with Doxorubicin above)

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.

Locations

Country	Name	City	State
United States	Hays Medical Center	Hays	Kansas
United States	University of Kansas Medical Center Cancer Center	Kansas City	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
University of Kansas Medical Center	Celgene Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathologic Complete Response		22 weeks