A Study of AC Followed by a Combination of Paclitaxel Plus Trastuzumab or Lapatinib or Both Given Before Surgery to Patients With Operable HER2 Positive Invasive Breast Cancer
Invasive Breast Cancer
About this trial
This is an interventional treatment trial for Invasive Breast Cancer focused on measuring HER2 positive breast cancer, invasive breast cancer, lapatinib, neoadjuvant, NSABP, paclitaxel, trastuzumab, doxorubicin, cyclophosphamide
Eligibility Criteria
Inclusion criteria:
- Female
- 18 years or older
- ECOG performance status of 0 or 1
- Primary breast tumor palpable and measures greater than or equal to 2.0 cm by physical exam
- Diagnosis of invasive adenocarcinoma made by core needle biopsy
- Breast cancer determined to be HER2-positive
- LVEF assessment by MUGA scan or ECG within 3 months prior to randomization
Blood counts must meet the following criteria:
- ANC greater than or equal to 1200/mm3
- Platelet count greater than or equal to 100,000/mm3
- Hemoglobin greater than or equal to 10 g/dL
- Serum creatinine less than or equal to ULN for the lab
Adequate hepatic function by these criteria:
- Total bilirubin less than or equal to the ULN for the lab unless the patient has a bilirubin elevation greater than ULN to 1.5 x ULN resulting from Gilbert's disease or similar syndrome due to slow conjugation of bilirubin; and
- Alkaline phosphatase less than or equal to 2.5 x ULN; and
- AST less than or equal to 1.5 x ULN for the lab.
- If skeletal pain present or alkaline phosphatase greater than ULN (but less than or equal to 2.5 x ULN), bone scan or PET scan must not demonstrate metastatic disease
- If AST or alkaline phosphatase greater than ULN , liver imaging (CT, MRI or PET scan) must not demonstrate definitive metastatic disease and the requirements in criterion for hepatic function must be met
- Able to swallow oral medications
Exclusion criteria:
- FNA alone to diagnose the primary tumor
- Excisional biopsy or lumpectomy was performed prior to randomization
- Surgical axillary staging procedure prior to randomization. Exceptions: 1) FNA or core biopsy of an axillary node for any patient, and 2) although not recommended, a pre-neoadjuvant therapy SN biopsy for patients with clinically negative axillary nodes.
- Tumors clinically staged as T4
- Ipsilateral cN2b or cN3 disease (Patients with cN1 or cN2a disease are eligible)
- Definitive clinical or radiologic evidence of metastatic disease
- Synchronous bilateral invasive breast cancer
- Requirement for chronic use of any of the medications or substances specified in the protocol
- Treatment including RT, chemotherapy, and/or targeted therapy for the currently diagnosed breast cancer prior to randomization
- Any sex hormonal therapy, e.g., birth control pills, ovarian hormone replacement therapy, etc. (These patients are eligible if therapy is discontinued prior to randomization)
- Continued therapy with any hormonal agent such as raloxifene, tamoxifen, or other SERM. (Patients are eligible only if these medications are discontinued prior to randomization)
- Prior history of breast cancer, including DCIS (Patients with a history of LCIS are eligible)
- Prior therapy with anthracyclines, taxanes, trastuzumab, or lapatinib for any malignancy
- Other malignancies unless the patient is considered to be disease-free for 5 or more years prior to randomization and is deemed by her physician to be at low risk for recurrence. Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinoma of the skin.
Cardiac disease that would preclude the use of the drugs included in the B-41 treatment regimens. This includes but is not confined to:
Active cardiac disease:
- angina pectoris requiring the use of anti-anginal medication;
- ventricular arrhythmias except for benign premature ventricular contractions controlled by medication;
- conduction abnormality requiring a pacemaker;
- supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication; and
- clinically significant valvular disease.
History of cardiac disease:
- myocardial infarction;
- congestive heart failure; or
- cardiomyopathy.
- Uncontrolled hypertension, defined as blood pressure greater than 150/90 mm/Hg on antihypertensive therapy
- History of or current symptomatic interstitial pneumonitis or pulmonary fibrosis or definitive evidence of interstitial pneumonitis or pulmonary fibrosis described on CT or chest x-ray in asymptomatic patients
- Sensory/motor neuropathy greater than or equal to grade 2, as defined by the NCI's CTCAE v3.0
- Malabsorption syndrome, ulcerative colitis, resection of the stomach or small bowel, or other disease significantly affecting gastrointestinal function
- Other non-malignant systemic disease that would preclude treatment with any of the treatment regimens or would prevent required follow-up
- Conditions that would prohibit administration of corticosteroids
- Administration of any investigational agents within 30 days before randomization
- Pregnancy or lactation
Sites / Locations
- MBCCOP, Gulf Coast
- Scripps Cancer Center-San Diego
- University of California, Irvine Medical Center
- Pacific Shores Medical Group
- St. Joseph Hospital
- Desert Regional Medical Center Comprehensive Cancer Center
- Stanford University Medical Center
- Sutter Medical Center
- Kaiser Permanente-San Diego
- Santa Rosa Memorial Hospital
- Kaiser Permanente-Vallejo
- University of Colorado Cancer Center
- Memorial Hospital
- Kaiser Permanente-Franklin
- CCOP-Colorado Cancer Research Prog. Inc.(Administrative Only)
- Kaiser Permanente Rock Creek
- Hartford Hospital
- Eastern Connecticut Hematology & Oncology Associates
- Sibley Memorial Hospital
- MD Anderson Cancer Center
- Phoebe Putney Memorial Hospital
- MBCCOP, Medical College of Georgia Research Institute
- University of Hawaii
- Kaiser Permanente Hawaii - Moanalua Med Center
- Kootenai Cancer Center
- Rush University Medical Center
- Decatur Memorial Hospital
- Cancer Institute at Alexian Brothers Hospital Network
- Edward Hospital
- Edward Cancer Center Plainfield
- CCOP, Central Illinois
- CCOP, Carle Cancer Center
- St. Vincent Hospital and Health Care Center
- CCOP, Northern Indiana Cancer Research Consortium
- CCOP, Des Moines, IA
- University of Iowa
- CCOP, Sioux Community Cancer consortium
- CCOP, Wichita KS
- University of Kentucky Medical Center
- NortonHealtcare Inc.
- CCOP, Ochsner Clinic Foundation
- Greater Baltimore Medical Center
- Franklin Square Hospital Center
- Boston Medical Center
- CCOP, Michigan Cancer Research Consortium
- Henry Ford Health System
- Henry Ford Hospital
- CCOP, Grand Rapids Clnical Oncology Program
- CCOP, Kalamazoo, MI
- Michigan State University - Breslin Cancer Center
- CCOP, William Beaumont Hospital
- Providence Hospital - Southfield
- Hennepin County Medical Center
- CCOP, Metro-Minnesota
- University of Missouri-Ellis Fischel
- CCOP, Kansas City (Administrative Only)
- CCOP, Ozark Health Ventures LLC
- Saint Louis UniversityHealth Sciences Center
- CCOP, Heartland Cancer Research
- CCOP, Montana Cancer Consortium
- CCOP, Missouri Valley Consortium
- Cancer Institute of New Jersey
- Newark Beth Israel Medical Center
- New York Oncology Hematology PC-Albany
- Cancer Center at Glens Falls Hospital
- CCOP, Hematology-Oncology Associates of CNY
- Alamance Regional Medical Center
- University of North Carolina at Chapel Hill
- CCOP, Southeast Cancer Control Consortium
- Alamance Regional Medical Center - Off site Clinic
- Wake Forest University School of Medicine
- Akron City Hospital
- Aultman Hospital
- Case Western Reserve/University Hospitals-Ireland Cancer Cntr.
- Ohio State University
- CCOP, Columbus, OH
- CCOP, Dayton, OH
- CCOP, Oklahoma
- Lehigh Valley Hospital
- Geisinger Clinic
- Hershey Medical Center
- Albert Einstein Healthcare Network
- Allegheny General Hospital/Allegheny-Singer Research Institute
- NSABP Foundation, Inc.
- University of Pittsburgh
- Western Pennsylvania Hospital
- Mercy Hospital
- Reading Hospital & Medical Center
- CCOP, Main Line Health
- CCOP, Upstate Carolina
- Sanford Cancer Center
- Thompson Cancer Survival Center-Dowell Springs
- Joe Arrington Cancer Research & Treatment Center
- University of Texas Health Science Center at San Antonio
- MBCCOP, Virginia Commonwealth University
- Puget Sound Oncology Consortium
- CCOP, Virginia Mason
- CCOP, Northwest
- West Virginia University Hospitals Inc.
- Camden-Clark Memorial Hospital
- Wheeling Hospital
- CCOP, Marshfield Clinic
- Medical College of Wisconsin
- Odette Cancer Centre
- Royal Victoria Hospital
- Jewish General Hospital
- St. Mary's Hospital Center
- University of Montreal Hospital Group
- Centre Hospitalier Affilie Universitaire De Quebec, Hospital du St-Sacrement
- MBCCOP, San Juan, Puerto Rico
Arms of the Study
Arm 1
Arm 2
Arm 3
Active Comparator
Experimental
Experimental
Group 1: AC then paclitaxel + trastuzumab
Group 2: AC then paclitaxel + lapatinib
Group 3: AC then paclitaxel + trastuzumab + lapatinib
AC followed by paclitaxel plus trastuzumab
AC followed by paclitaxel plus lapatinib
AC followed by paclitaxel plus trastuzumab plus lapatinib