Breast Cancer
Conditions
Keywords
invasive breast cancer, HER2, primary breast cancer, neo-adjuvant therapy, Trastuzumab, Nab-paclitaxel
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.
Interventions
DRUGnab-paclitaxel
100 MG/M2 IV over 30 minutes once a week for 12 weeks
DRUGtrastuzumab
4 MG loading dose followed by 2 MG/KG every week for a total of 12 weeks
DRUGDoxorubicin
60 MG/M2 every two weeks for a total of 4 cycles
DRUGcyclophosphamide
600 MG/M2 every 2 weeks for 4 cycles (administered with Doxorubicin above)
BIOLOGICALGrowth 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.
PROCEDURESurgery
* 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.
Sponsors
Celgene Corporation
University of Kansas Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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.
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pathologic Complete Response | 22 weeks |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intervention Arm Nab-paclitaxel, trastuzumab, doxorubicin, cyclophosphamide, Growth Factor Support, Surgery
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)
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.
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. | 32 |
| Total | 32 |
Baseline characteristics
| Characteristic | Intervention Arm |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 29 Participants |
| Sex: Female, Male Female | 32 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 32 / 32 |
| serious Total, serious adverse events | 5 / 32 |
Outcome results
Primary
Pathologic Complete Response
Time frame: 22 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intervention Arm | Pathologic Complete Response | 26 percentage of participants |