A Randomized Phase III Trial Evaluating the Role of Axillary Lymph Node Dissection in Breast Cancer Patients (cT1-3 N1) Who Have Positive Sentinel Lymph Node Disease After Neoadjuvant Chemotherapy

Location:

Jacksonville, Fla.

Trial status:

Open for Enrollment

Why is this study being done?

All patients will undergo surgery to identify sentinel lymph node(s). If a sentinel lymph node is determined to be positive on intra-operative pathology the patient will be registered/randomized intra-operatively. Patients who do not have a sentinel lymph node identified will not be registered/randomized to the study. Patients whose sentinel lymph is found to be negative intra-operatively and have not undergone ALND, but had at least one sentinel lymph node found to be positive on final pathology review will be registered/randomized post-operatively. After patient registration/randomization, if negative surgical margins are not achieved at the completion of all breast surgeries then the patient will discontinue protocol treatment. Patients with hormone receptor (ER and/or PR) positive disease should receive a minimum of 5 years of standard endocrine therapy (experimental agents/regimens are not permitted). Endocrine therapy should begin following completion of neoadjuvant chemotherapy and surgery, either before, during or after radiation therapy at the discretion of the oncologist. Selection of the agents is at the treating physician's discretion. Patients with HER 2 positive disease (on tumor markers obtained either prior to NAC or on surgical pathology) should complete a total of one year of trastuzumab therapy (over the neoadjuvant and adjuvant period). Chemotherapy, biologic therapy or vaccine therapy in the adjuvant setting is not allowed. Patients who wish to receive any of these therapies after surgery must go off study at the time of their initiation. Primary Objective: - To evaluate whether radiation to the undissected axilla and regional lymph nodes is not inferior to axillary lymph node dissection with radiation to the regional lymph nodes but not to the dissected axilla in terms of invasive breast cancer recurrence-free interval in patients with positive SLN(s) after completion of neoadjuvant chemotherapy Secondary Objectives: - To evaluate whether radiation to the undissected axilla and regional lymph nodes is not inferior to axillary lymph node dissection with radiation to the regional lymph nodes but not to the dissected axilla in terms of the incidence of invasive loco-regional recurrences in patients with a positive SLN(s) after completion of neoadjuvant chemotherapy - To obtain an estimate of the distribution of residual disease burden scores. - To estimate the distribution of overall survival. Patients are followed up for 5 years after completion of radiation therapy.

Who is eligible to participate?

Pre-Registration Eligibility Criteria: - Patients ≥ 18 years of age - Clinical stage T1-3 N1 M0 breast cancer at diagnosis (prior to the start of neoadjuvant chemotherapy) by American Joint Committee on Cancer (AJCC) staging 7th edition. - No inflammatory breast cancer. - No other malignancy within 5 years of registration with the exception of basal cell or squamous cell carcinoma of the skin treated with local resection only or carcinoma in situ of the cervix - All patients must have had an axillary ultrasound with fine needle aspiration (FNA) or core needle biopsy of axillary lymph nodes documenting axillary metastasis at the time of diagnosis, prior to neoadjuvant chemotherapy. - Patients must have had estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2) status by immunohistochemistry [IHC] or fluorescence in situ hybridization [FISH] evaluated on diagnostic core biopsy prior to start of neoadjuvant chemotherapy. - Patients must have completed all planned chemotherapy prior to surgery. Sandwich chemotherapy is not allowed (i.e. chemotherapy planned to be given after surgery). Patients must have completed at least 6 cycles of neoadjuvant chemotherapy consisting of an anthracycline and/or taxane-based regimen without evidence of disease progression in the breast or the lymph nodes. - Patients with HER-2 positive tumors must have received neoadjuvant trastuzumab, trastuzumab + pertuzumab, or other approved anti-HER-2 therapy (either with all or with a portion of the neoadjuvant chemotherapy regimen). Therapy must be Food and Drug Administration (FDA)-approved targeted anti-HER2 therapy, but additional therapies are allowed as are non-trastuzumab regimens if administered in the context of an Institutional Review Board (IRB)-approved clinical trial. - All patients must have a clinically negative axilla (no palpable lymph nodes or bulky adenopathy) on physical examination documented at the completion of neoadjuvant chemotherapy. - No neoadjuvant endocrine therapy. - No neoadjuvant radiation therapy. - No sentinel lymph node (SLN) surgery/excisional biopsy for pathological confirmation of axillary status prior to or during neoadjuvant chemotherapy. - No prior history of ipsilateral breast cancer (invasive disease or ductal carcinoma in situ [DCIS]). Lobular carcinoma in situ (LCIS) and benign breast disease is allowed. - No prior ipsilateral axillary surgery, such as excisional biopsy of lymph node(s) or treatment of hidradenitis. - No history of prior or concurrent contralateral invasive breast cancer. Benign breast disease, LCIS or DCIS of contralateral breast is allowed. - Patients must not be pregnant or nursing. A negative pregnancy test is required prior to registration for women of childbearing potential. Note: Peri-menopausal women must be amenorrheic for > 12 months to be considered not of childbearing potential. - Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status 0-1. - Required Pre-Registration Laboratory Values: 1. Serum or urine beta-human chorionic gonadotropin (ß-HCG) 2. Negative in women of child-bearing potential Intra-Operative Registration/Randomization Criteria: - Breast surgery (lumpectomy or mastectomy) and sentinel lymph node surgery must be completed within 56 days of the completion of neoadjuvant chemotherapy. - A minimum of 2 or a maximum of 6 sentinel nodes are identified and excised by the surgeon. Patients who do not have an identifiable sentinel lymph node will not proceed to Registration/Randomization. - At least one sentinel lymph node with a metastasis greater than 0.2 mm in greatest dimension identified on intra-operative pathologic assessment. Note: Isolated tumor cells (metastases less than or equal to 0.2 mm) will be treated as node negative disease (N0i+). Axillary lymph node dissection [ALND] is not to be performed prior to Registration/Randomization. Post-Operative Registration/Randomization Criteria: - For cases where ALND has not been performed and one of the following is true: 1. intra-operative evaluation of sentinel lymph node could not be/was not performed and final pathology identified a positive SLN with metastasis greater than 0.2 mm on hematoxylin and eosin stain (H & E) OR 2. sentinel lymph node on intra-operative evaluation considered negative was found to be positive on final pathology (with metastasis greater than 0.2 mm on H & E). - Breast surgery (lumpectomy or mastectomy) and sentinel lymph node surgery must be completed within 56 days of the completion of neoadjuvant chemotherapy. - At least one lymph node with a metastasis greater than 0.2 mm in greatest dimension identified by H&E staining on final pathology (for cases where intra-operative evaluation was not performed, or was negative and complete dissection was not performed). - Among the minimum of 2 and the maximum of 6 sentinel nodes identified and excised by the surgeon, no more than 8 lymph nodes (sentinel and non-sentinel) were found by the pathologists to have been actually excised. Note: Isolated tumor cells (metastases less than or equal to 0.2 mm) will be treated as node negative disease (N0i+). - For those patients who also undergo contralateral breast surgery, if invasive disease is found in the contralateral breast, the patient is not eligible for registration/randomization.

Last updated:

6/25/2014

NCT ID:

NCT01901094

IRB Number:

13-006433