|Phase III||Biomarker/Laboratory analysis, Treatment||Closed||18 and over||NCI||NCI-2009-01073|
CALGB 40601, CDR0000616648, U10CA031946, NCT00770809
This randomized phase III trial is studying paclitaxel to see how well it works when given together with trastuzumab and/or lapatinib in treating patients with stage II or stage III breast cancer that can be removed by surgery. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving paclitaxel together with trastuzumab and/or lapatinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known which regimen is more effective in treating patients with breast cancer.
Further Study Information
I. To determine if the pathologic complete response (pCR) in the breast to neoadjuvant weekly paclitaxel with trastuzumab plus lapatinib (THL) is 20% greater than the pCR to weekly paclitaxel with trastuzumab alone (TH).
I.To determine the pathologic complete response in the breast and axilla, using AJCC TMN criteria (Version 6), to neoadjuvant weekly paclitaxel plus HER2- targeted therapy in patients with HER2-positive operable breast cancer.
II. To evaluate residual cancer burden (RCB) as a predictor of long term relapse free survival (RFS) and overall survival (OS).
III. To document the toxicity of all chemotherapeutic regimens (THL, TH). IV. To determine the correlation between clinical, radiographic and pathologic response.
V. To compare overall survival (OS), relapse free survival (RFS) and time to first failure (TFF) among the treatment groups. OS and TFF will be measured for all patients from study registration. RFS will be measured from definitive surgery for those patients who undergo definitive surgery.
VI. To obtain blood, fresh frozen and fixed tumor tissue to test specific hypotheses for which biomarker data exist and to evaluate biomarkers in blood, serum and tissue that are likely to influence response to and toxicity of trastuzumab alone or trastuzumab plus lapatinib, when given with paclitaxel.
VII. To determine the surgical practice patterns for breast conservation and sentinel lymphadenectomy in patients undergoing neoadjuvant chemotherapy.
VIII. To determine the radiotherapy practice patterns for post-mastectomy and regional nodal irradiation in patients undergoing neoadjuvant chemotherapy.
IX. To evaluate pharmacogenomic determinants of toxicity.
OUTLINE: Patients are randomized to 1 of 3 treatment arms.
ARM I: Patients receive trastuzumab IV over 30-90 minutes and paclitaxel IV over 1 hour once weekly and lapatinib ditosylate orally (PO) once daily for 16 weeks in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive trastuzumab and paclitaxel as in arm I.
ARM III: Patients receive paclitaxel and lapatinib ditosylate as in arm I. (Discontinued as of 6-15-11) Within 42 days after completion of neoadjuvant therapy, patients in both arms undergo definitive surgery (breast conservation or total mastectomy).
After completion of study treatment, patients are followed every 6 months for 2 years and then annually for up to 10 years.
- Pathologically confirmed invasive breast cancer by core needle or incisional biopsy
- Clinical stage II or III disease
- Resectable disease
- HER2- positive tumor, defined as 3+ over expression by immunohistochemistry (IHC) or gene amplification by fluorescence in situ hybridization (FISH) with a ratio of >= 2 on invasive tumor
- Measurable disease, defined as target lesion in the breast >= 1 cm by physical examination or radiographic measurement
- No axillary disease only
- Multicentric or bilateral disease allowed provided the target lesion meets eligibility criteria
- Planning to undergo surgical resection after neoadjuvant therapy
- No inflammatory breast cancer
- No metastatic disease
- Concurrent enrollment in CALGB-150702 required
- Hormone receptor status known
- Menopausal status not specified
- Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status 0-1
- Absolute neutrophil count (ANC) >= 1,000/mm^3
- Platelet count >= 100,000/mm^3
- Bilirubin =< 1.5 times upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective non-hormonal contraception during and for >= 2 months after completion of study treatment
- Cardiac ejection fraction >= 50% by echocardiogram or multiple gated acquisition (MUGA) scan
- Willing to undergo pretreatment biopsies and submit archival tissue obtained at the time of surgery
- No concurrent pegfilgrastim
- No prior chemotherapy, hormonal therapy, biologic therapy, or radiotherapy for the treatment of breast cancer
- No other concurrent chemotherapy or hormonal therapy, except for the following:
- Steroids for adrenal failure
- Hormones for non-disease-related conditions (e.g., insulin for diabetes)
- Intermittent use of dexamethasone as an antiemetic
Trial Lead Organizations/Sponsors
National Cancer Institute
|Lisa Carey||Principal Investigator|
|Cotton-O'Neil Cancer Center|
|David E Einspahr||Ph: 785-270-4963|
|St. Mary's Regional Cancer Center at St. Mary's Medical Center|
|Arvinder S Bir||Ph: 888-823-5923|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00770809
Information obtained from ClinicalTrials.gov on March 26, 2013
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