NCTN: A Double-Blind Phase III Trial of Doxorubicin and Cyclophosphamide followed by Paclitaxel with Bevacizumab or Placebo in Patients with Lymph Node Positive and High Risk Lymph Node Negative Breast Cancer (E5103)

Study ID: E5103 NCT Number: NCT00433511ECOG-ACRIN Cancer Research GroupSubmitted in collaboration with the NCTN/NCORP Data ArchiveTrial Title: NCTN: A Double-Blind Phase III Trial of Doxorubicin and Cyclophosphamide followed by Paclitaxel with Bevacizumab or Placebo in Patients with Lymph Node Positive and High Risk Lymph Node Negative Breast Cancer Trial Description: This randomized phase III trial studies doxorubicin hydrochloride, cyclophosphamide, and paclitaxel to see how well they work with or without bevacizumab in treating patients with cancer that has spread to the lymph nodes (lymph node-positive) or cancer that has not spread to the lymph nodes but is at high risk for returning (high-risk, lymph node-negative breast cancer). Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, and paclitaxel, 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. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of breast cancer by blocking blood flow to the tumor. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery and help prevent the tumor from returning. It is not yet known whether doxorubicin hydrochloride, cyclophosphamide, and paclitaxel are more effective with or without bevacizumab. You are encouraged to view the PDF data dictionaries found in the “Documents” tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication.Clinical data presented in the following publication(s): PMID 30040523PMID 30054636PMID 24584876Disease type(s): Breast Neoplasm - Breast Cancer - Invasive Clinical dataset(s) included: NCT00433511-D1 (PMID 30040523): There are three datasets for PMID 30040523 (-D1, -D2, and -D4). This dataset, NCT00433511-D1, contains baseline characteristics, treatment and follow up information, cardiac function measures, and efficacy data. Dataset NCT00433511-D2 contains toxicity data. Dataset NCT00433511-D4 contains updated time-to-event data that have undergone further data cleaning from those in NCT00433511-D1. NCT00433511-D2 (PMID 30040523): There are three datasets for PMID 30040523 (-D1, -D2, and -D4). This dataset, NCT00433511-D2, contains toxicity data. Dataset NCT00433511-D1 contains baseline characteristics, treatment and follow up information, cardiac function measures, and efficacy data. Dataset NCT00433511-D4 contains updated time-to-event data that have undergone further data cleaning from those in NCT00433511-D1.NCT00433511-D3 (PMID 30054636): This dataset, NCT00433511-D3, contains the data used to generate the results in PubMed ID PMID: 30054636; PMCID: PMC6385891, a non-primary publication from trial NCT00433511 looking at association of circulating tumor cells with late recurrence of ER+ breast cancer. Data include limited baseline characteristics, CTC results, time-to-recurrence data, and follow-up information. Data that are identical to those presented in NCT00433511-D1 (for the trial's primary publication, PMID 30040523) are not duplicated here in this dataset for NCT00433511-D3.NCT00433511-D4 (PMID 30040523): There are three datasets for PMID 30040523 (-D1, -D2, and -D4). This dataset, NCT00433511-D4, contains updated variables ttchf, ttbev, and os that have undergone further data cleaning from those in Dataset NCT00433511-D1 which corresponds to data used to generate the results for PMID 30040523. Dataset NCT00433511-D2 contains toxicity data.NCT00433511-D5 (Unpublished): Dataset NCT00433511-D5 contains data on time to local-regional recurrence and time to distant recurrence that were collected on the trial, but not published. NCT00433511-D6 (PMID 24584876): This dataset, NCT00433511-D6, contains the data published in PMID 24584876, a publication focusing on a subgroup of patients from ECOG-ACRIN trial E5103 (women who were premenopausal at enrollment, responded to the 12-month survey, had not undergone bilateral oophorectomy or ovarian function suppression before that survey, and had serum banked for research before chemotherapy). Data includes limited patient characteristics and amenorrhea indicators. Data that are identical to those presented in NCT00433511-D1 (for the trial's primary publication, PMID 30040523) are not duplicated in the NCT00433511-D6 dataset. Additional correlative data are available for this trial under phs003201. ]]>
NCT00433511 D1 Data DictionaryNCT00433511 D2 Data DictionaryNCT00433511 D3 Data DictionaryNCT00433511 D4 Data DictionaryNCT00433511 D5 Data DictionaryNCT00433511 D6 Data DictionaryInclusion Criteria: Patients must have histologically confirmed adenocarcinoma of the breast at significant risk of distant recurrence based on at least one of the following criteria:For axillary lymph node positive disease:Involvement of at least one sentinel or axillary lymph node on routine histologic examination; patients with negative sentinel nodes and negative axillary nodes or involvement only demonstrated by immunohistochemistry are not eligible unless they meet one of the other eligibility criteria belowNOTE: consider intramammary nodes as equivalent to axillary nodes for the purposes of eligibility and stratificationFor axillary lymph node negative disease:Estrogen receptor (ER) negative tumor >= 1 cmER+ tumor >= 5 cm regardless of recurrence scoreER+ tumor >= 1 cm but < 5 cm with a recurrence score >= 11 (patients enrolled in the TAILORx trial are eligible)NOTE: axillary dissection is strongly encouraged in patients with lymph node involvement identified on sentinel node biopsyPatients must have completed definitive breast surgery including total mastectomy and axillary dissection (modified radical mastectomy), total mastectomy and sentinel node biopsy, breast conservation surgery and axillary dissection or breast conservation surgery and sentinel node biopsyNOTE: breast conservation surgery includes lumpectomy, partial mastectomy, and excisional biopsyMargins of breast conservation surgery or mastectomy must be histologically free of invasive breast cancer and ductal carcinoma in situ (DCIS); patients with resection margins positive for lobular carcinoma in situ (LCIS) are eligibleTime from last surgery for breast cancer (breast conservation surgery, mastectomy, sentinel node biopsy, axillary dissection or re-excision of breast conservation surgery margins) to planned treatment start date must be > 28 days and =< 84 daysEastern Cooperative Oncology Group (ECOG) performance status 0-1Within =< 8 weeks prior to randomization: Absolute neutrophil count >= 1,000/mm^3Within =< 8 weeks prior to randomization: Platelet count >= 100,000/mm^3Within =< 8 weeks prior to randomization: Total bilirubin =< 1.5 mg/dLWithin =< 8 weeks prior to randomization: Aspartate aminotransferase (AST) =< 2 times upper limit of normal(ULN)Within =< 8 weeks prior to randomization: Serum creatinine =< 1.5 mg/dLWithin =< 8 weeks prior to randomization: Urine protein:creatinine ratio < 1.0 or 24-hour proteinWithin =< 8 weeks prior to randomization: Partial thromboplastin time (PTT) =< 1.5 times ULNWithin =< 8 weeks prior to randomization: Left ventricle ejection fraction (LVEF) >= institutional limits of normal by multigated acquisition scan (MUGA) or echocardiogram (ECHO)Patients who have undergone breast conservation surgery must receive radiation; prior to randomization, the investigator must specify the planned radiation technique:Whole breast radiation (WBRT) after chemotherapyAccelerated partial breast radiation (APBI) after chemotherapyAccelerated partial breast radiation (APBI) prior to chemotherapyNOTE: if APBI was completed prior to study entry, day 1 of protocol therapy must be at least 4 weeks after the completion of APBIPost-mastectomy radiation therapy (RT) is required for all patients with a primary tumor of >= 5 cm or involvement of 4 or more lymph nodes; post-mastectomy RT may be administered at the investigator's discretion for all other mastectomy patientsPatients with human epidermal growth factor receptor (HER)2 + (3+ by immunohistochemistry [IHC] or fluorescent in situ hybridization [FISH] ratio >= 2) breast cancer are not eligiblePatients with synchronous bilateral breast cancer (diagnosed within one month) are eligible if the higher tumor, node, metastasis (TNM) stage tumor meets the eligibility criteria for this trialPatients must not have clinical evidence of inflammatory disease or fixed axillary nodes at diagnosisPatients must not have received prior cytotoxic chemotherapy or hormonal therapy for this breast cancer; prior treatment with an anthracycline, anthracenedione or taxane for any condition is not allowedNOTE: prior use of tamoxifen for chemoprevention is allowed but must be discontinued at study entry; similarly, prior raloxifene use is allowed but must be discontinued at study entryPatients must not have had any major surgical procedure within 28 days of planned treatment start dateNOTE: non-operative biopsy or placement of a vascular access device is not considered a major surgeryPatients may not have had placement of a vascular access device within 24 hours of planned day 1 of treatmentPatients must not have clinically significant cardiovascular or cerebrovascular disease, including:Any history ofCerebrovascular disease including transient ischemic attack (TIA), stroke or subarachnoid hemorrhageIschemic bowelWithin the last 12 monthsMyocardial infarctionUnstable anginaNew York Heart Association (NYHA) class II or greater congestive heart failureGrade II or greater peripheral vascular diseaseUncontrolled hypertension defined as systolic blood pressure (SBP) > 160 or diastolic blood pressure (DBP) > 90Uncontrolled or clinically significant arrhythmiaNOTE: blood pressure must be obtained within =< 8 weeks prior to randomizationNOTE: patients with controlled atrial fibrillation are eligiblePatients who require full-dose anticoagulation may enroll provided they meet the following criteria:The patient must have an in-range international normalized ratio (INR) (usually between 2 and 3) on a stable dose of warfarin or be on stable dose of low molecular weight (LMW) heparinThe patient must not have active bleeding or pathological conditions that carry high risk of bleeding (e.g. varices)NOTE: prophylactic use of anticoagulants to maintain patency of a vascular access device is permittedPatients must not have a bleeding diathesis, hereditary or acquired bleeding disorder or coagulopathyPatients must not have a non-healing wound or fracture; patients with an abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to randomization are not eligiblePatients must not have hypersensitivity to paclitaxel or drugs using the vehicle Cremophor, Chinese hamster ovary cell products or other recombinant human antibodiesWomen must not be pregnant or breast-feeding; all females of childbearing potential must have a blood or urine test within 7 days prior to randomization to rule out pregnancyWomen of childbearing potential and sexually active males must use an accepted and effective method of contraception ]]>