A Randomized Phase III Trial of Adjuvant Therapy Comparing Chemotherapy Alone (Six Cycles of Docetaxel Plus Cyclophosphamide or Four Cycles of Doxorubicin Plus Cyclophosphamide Followed by Weekly Paclitaxel) to Chemotherapy Plus Trastuzumab in Women With Node-Positive or High-Risk Node-Negative HER2-Low Invasive Breast Cancer
This randomized phase III clinical trial studies chemotherapy with or without trastuzumab after surgery to see how well they work in treating women with invasive breast cancer. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) and giving chemotherapy after surgery may kill more tumor cells. Monoclonal antibodies, such as trastuzumab, can block cancer 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. It is not yet known whether combination chemotherapy is more effective with trastuzumab in treating breast cancer.
Stanford is not currently accepting new patients for this trial. You may want to check clinicaltrials.gov to see if other locations are recruiting.
- biological : trastuzumab
- drug : docetaxel
- drug : cyclophosphamide
- drug : doxorubicin hydrochloride
- drug : paclitaxel
- other : laboratory biomarker analysis
- other : quality-of-life assessment
Phase: Phase 3
Ages Eligible For Study:
- Patients should have a life expectancy of at least 10 years, excluding their diagnosis of breast cancer; (comorbid conditions should be taken into consideration, but not the diagnosis of breast cancer) - Women of reproductive potential must agree to use an effective non-hormonal method of contraception (for example condoms, some intrauterine devices, diaphragms, tubal ligation, vasectomized partner, or abstinence) during therapy and for at least 6 months (Arm 1 patients) and for at least 7 months (Arm 2 patients) after the last dose of study therapy (chemotherapy or trastuzumab) - Submission of tumor samples from the breast surgery is required for all patients; therefore, the local pathology department policy regarding release of tumor samples must be considered in the screening process; patients whose tumor samples are located in a pathology department that by policy will not submit any samples for research purposes should not be approached for participation in the B-47 trial - The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines - Eastern Cooperation Oncology Group (ECOG) performance status of 0 or 1 - The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination - All of the following staging criteria (according to the 7th edition of the American Joint Committee on Cancer [AJCC] Cancer Staging Manual) must be met: - By pathologic evaluation, primary tumor must be pT1-3 - By pathologic evaluation, ipsilateral nodes must be pN0, pN1 (pN1mi, pN1a, pN1b, pN1c), pN2a, pN2b, pN3a, or pN3b - If pN0, one of the following criteria must be met: - pT2 and estrogen receptor (ER) negative and progesterone receptor (PgR) negative; or - pT2 and ER positive (PgR status may be positive or negative) and either grade 3 histology or Oncotype DX Recurrence Score of >= 25; or - pT3 regardless of hormone receptor status, histologic grade, and Oncotype DX Recurrence Score - HER2 status of the primary tumor must be evaluated prior to randomization; all testing performed must indicate that the tumor is HER2-low as defined below - IHC must be performed and the IHC staining results must indicate a score of 1+ (in situ hybridization [ISH] testing is not required) or 2+ (ISH must also be performed and must indicate that the tumor is HER2-low as described below) - If ISH testing is performed, test results must be as follows and IHC must be 1+ or 2+: the ratio of HER2 to chromosome enumeration probe 17 (CEP17) must be < 2.0 or, if a ratio was not performed, the HER2 gene copy number must be < 4 per nucleus - Note: If the IHC staining intensity is reported as a range, e.g., 0 to 1+ or 1+ to 2+, the higher intensity score in the range should be used to determine eligibility - The patient must have undergone either a total mastectomy or breast-conserving surgery (lumpectomy); (patients who have had a nipple-sparing mastectomy are eligible) - For patients who undergo lumpectomy, the margins of the resected specimen must be histologically free of invasive tumor and ductal carcinoma in situ (DCIS) as determined by the local pathologist; if pathologic examination demonstrates tumor at the line of resection, additional operative procedures may be performed to obtain clear margins; if tumor is still present at the resected margin after re-excision(s), the patient must undergo total mastectomy to be eligible; (patients with margins positive for lobular carcinoma in situ [LCIS] are eligible without additional resection) - For patients who undergo mastectomy, margins must be free of gross residual tumor; (patients with microscopic positive margins are eligible as long as post-mastectomy radiation therapy [RT] of the chest wall will be administered) - The patient must have completed one of the procedures for evaluation of pathologic nodal status listed below: - Sentinel lymphadenectomy alone: - If pathologic nodal staging based on sentinel lymphadenectomy is pN0 or pN1b - If pathologic nodal staging based on sentinel lymphadenectomy is pN1mi or pN1a, the primary tumor must be T1 or T2 by pathologic evaluation and the nodal involvement must be limited to 1 or 2 positive nodes - Sentinel lymphadenectomy followed by removal of additional non-sentinel lymph nodes if the sentinel node (SN) is positive; or - Axillary lymphadenectomy with or without SN isolation procedures - The interval between the last surgery for breast cancer (treatment or staging) and randomization must be no more than 84 days - The patient must have ER analysis performed on the primary tumor prior to randomization; if ER analysis is negative, then PgR analysis must also be performed (either the core biopsy or surgical resection specimen can be used for ER/PgR testing); patients with a primary tumor that is hormone receptor-positive or receptor-negative are eligible - Absolute neutrophil count (ANC) must be >= 1,200/mm^3 - Platelet count must be >= 100,000/mm^3 - Hemoglobin must be >= 10 g/dL - Total bilirubin must be =< upper limit of normal (ULN) for the lab unless the patient has a bilirubin elevation > ULN to 1.5 x ULN due to Gilbert disease or similar syndrome involving slow conjugation of bilirubin - Alkaline phosphatase must be =< 2.5 x ULN for the lab - Aspartate aminotransferase (AST) must be =< 1.5 x ULN for the lab (if alanine aminotransferase [ALT] is performed instead of AST [per institution's standard practice], the alanine aminotransferase [ALT] value must be =< 1.5 x ULN; if both were performed, the AST must be =< 1.5 x ULN) - Alkaline phosphatase and AST may not both be > the ULN - Patients with AST or alkaline phosphatase > ULN are eligible for inclusion in the study if liver imaging (computed tomography [CT], magnetic resonance imaging [MRI], positron emission tomography [PET]-CT, or PET scan) performed within 90 days prior to randomization does not demonstrate metastatic disease and the above requirements are met - Patients with alkaline phosphatase that is > ULN but =< 2.5 x ULN or unexplained bone pain are eligible for inclusion in the study if a bone scan, PET-CT scan, or PET scan performed within 90 days prior to randomization does not demonstrate metastatic disease - The most recent postoperative serum creatinine performed within 6 weeks prior to randomization must be =< ULN for the lab - Left ventricular ejection fraction (LVEF) assessment must be performed within 90 days prior to randomization; LVEF assessment performed by 2-dimensional (D) echocardiogram is preferred, however, multi-gated acquisition (MUGA) scan maybe substituted based on institutional preferences - For patients who will receive the TC chemotherapy regimen, the LVEF must be >= 50% regardless of the cardiac imaging facility's lower limit of normal - For patients who will receive the AC-->WP chemotherapy regimen, the LVEF must be >= 55% regardless of the cardiac imaging facility's lower limit of normal - NOTE: Since the pre-entry LVEF serves as the baseline for comparing subsequent LVEF assessments, it is critical that this baseline study be an accurate assessment; if the baseline LVEF is > 70%, the investigator is encouraged to have the accuracy of the initial LVEF result confirmed and repeat the test if the accuracy is uncertain