Neoadjuvant Biweekly Doxorubicin and Cyclophosphamide With GMCSF Followed by Weekly Carboplatin/Nab-paclitaxel Plus or Minus Trastuzumab and Plus or Minus Bevacizumab in Treatment of Large or Inflammatory Breast Cancer-a Phase II Study

University of California, Irvine1 个研究点分布在 1 个国家目标入组 43 人开始时间: 2005年10月最近更新: 2019年2月28日

适应症

干预措施

试验速览

阶段: 2 期
状态: 已完成
发起方: University of California, Irvine
入组人数: 43
试验地点: 1
主要终点: Overall Clinical Response to the Dose Dense Regimen

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Study Aims

To measure the clinic response rates in patients with breast cancer more than 2 cm and/or lymph node positive breast cancer treated with 2-4 cycles of biweekly doxorubicin, cyclophosphamide with Granulocyte-macrophage colony-stimulating factor (GM-CSF) (days 4-13) followed by weekly carboplatin/nab-paclitaxel given for 3 weeks, followed by 1 week of rest, for a total of 9-12 doses. (Her-2 positive patients, in addition, will receive Trastuzumab weekly (12-16 doses) and Her-2 negative patients will receive Bevacizumab (6-8 doses) q 2 weeks).
To measure the microscopic pathological response rate of this regimen.
To measure toxicity and the delivered dose intensity of this regimen.
To assess the association between microscopic pathologic complete response and clinical complete response at the primary tumor site in these patients.
To determine whether the GM-CSF increases the post treatment dendritic cells (S100+) percentage in the tumor draining lymph node as compared to pretreatment S100+ cells.
To determine whether the patients with a higher percent S100+ have a better clinical, pathological response, Disease Free Survival (DFS), and overall Survival (OS).
To determine whether flow cytometry of dendritic cells performed post-treatment in blood sample shows an increase in dendritic cell population compared to pretreatment levels.

详细描述

Background

Neoadjuvant chemotherapy, also termed primary, induction, or preoperative chemotherapy, is defined as chemotherapy administered before locoregional treatment. It was first used in locally advanced breast cancer 30 years ago. Classically, these tumors were treated with radical surgery and/or radiotherapy. However, despite this aggressive local therapy, most patients relapsed with distant metastases and eventually died. The aim of neoadjuvant therapy is to reduce the tumor volume in patients before surgical resection, thus increasing the likelihood of breast conservation. More recently, neoadjuvant therapy has been studied as a way of testing the relevance of biological markers in predicting disease outcome.

At least six randomized trials have compared survival in patients managed with either the neoadjuvant or adjuvant approaches. Two of the smaller trials suggested a survival advantage for patients treated with neoadjuvant chemotherapy. Other studies, including the largest trial (1,523 patients) run by the National Surgical Adjuvant Breast and Bowel Project (NSABP), found no differences in disease-free and overall survival.

Induction of a Polymerase chain reaction (pCR) should be one of the primary goals of neoadjuvant therapy because patients with no evidence of tumor cells in breast and lymph nodes after treatment may have a longer disease-free and overall survival.

Biweekly and weekly regimens may enhance dose intensity by minimizing re-growth of cells between cycles of treatment. In fact, dose dense regimens have even shown a survival benefit in an adjuvant setting in lymph node positive breast cancer, made possible with the use of G-CSF. There is no best standard neoadjuvant treatment yet. Generally patients receive AC (NSABP 14) on 3-weekly regimens in the neoadjuvant setting. In addition, incorporation of taxanes on a 3 weekly schedule has resulted in statistically higher pathological CR. More recently, weekly paclitaxel regimens have reported increased pathological responses compared to 3 weekly taxane regimens. Carboplatin has also emerged as an effective agent in the treatment of metastatic breast cancer. Moreover, the combination of carboplatin and paclitaxel has been found to be synergistic both in three-weekly regimens and weekly regimens. In fact, the combination of carboplatin, paclitaxel and trastuzumab has demonstrated a survival advantage over paclitaxel and trastuzumab alone. The Phase III study, which the preliminary results were presented at the San Antonio Breast Cancer Symposium, show that the addition of carboplatin to trastuzumab and paclitaxel resulted in a six-month improvement in the time it took for the disease to progress, compared to the standard trastuzumab and paclitaxel regimen. The study found the median survival in the trastuzumab and paclitaxel arm was 33.5 months, while the group receiving the tripartite therapy had yet to reach that point after 36 months of follow-up. Furthermore, the weekly regimens of these drugs have been found to have significantly improved tolerability over three weekly regimens. Therefore, we propose to use 2-4 cycles of AC q 2 weeks, as used in the dose dense adjuvant study with GM-CSF support on days 4-13 of the cycle. After the completion of AC we plan to administer taxol and carboplatin weekly for a total of 9-12 doses with a one-week rest after every 3 weeks of treatment over 12 weeks.

研究设计

研究类型: Interventional
分配方式: Na
干预模型: Single Group
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: Female
接受健康志愿者: 否

入选标准

•Patients must be women with a histologically confirmed diagnosis of breast cancer that is more than 2 cm and/or lymph node positive. Histologic confirmation shall be by either core needle biopsy or incisional biopsy. Punch biopsy is allowed if invasive breast cancer is documented.
•Patients must meet one of the criteria defined below (indicate one):
•Selected Stage IIB (T3, N0, M0) or IIIA (T3, N1-2, M0) disease judged primarily unresectable by an experienced breast surgeon; or otherwise deemed - appropriate candidates for neoadjuvant treatment.
•Stage IIIB (T4, Any N, M0) or (Any T, N3, M0) disease.
•Physical examination, chest x-ray and any x-rays or scans needed for tumor assessment must be performed within 90 days prior to registration.
•All patients must have a multiple gated acquisition (MUGA) scan or echocardiogram scan performed within 90 days prior to registration and left ventricular ejection fraction (LVEF) percentage must be greater than the institutional lower limit of normal.
•Patients must have a serum creatinine and bilirubin ≤ the institutional upper limit of normal, and an serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) ≤ 2x the institutional upper limit of normal. These tests must have been performed within 90 days prior to registration.
•Patients must have an absolute neutrophil count (ANC) of ≥ 1,500/μl and a platelet count of ≥ 100,000/μl. These tests must have been performed within 90 days prior to registration.
•Patients must have a performance status of 0-2 by Zubrod criteria
•In calculating days of tests and measurements, the day a test or measurement is done is considered Day
•Therefore, if a test is done on a Monday, the Monday four weeks later would be considered Day
•This allows for efficient patient scheduling without exceeding the guidelines. If Day 28 or 42 falls on a weekend or holiday, the limit may be extended to the next working day.
•All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.

排除标准

•Patients with the clinical diagnosis of congestive heart failure or angina pectoris are NOT eligible.
•Pregnant or nursing women may not participate due to the possibility of fetal harm or of harm to nursing infants from this treatment regimen. Women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. A urine pregnancy test is required for women of childbearing potential.