8 Continuous vs 8 Intermittent Cycles in First and Second Line Treatment of Patients With HER2/Neu Negative, Incurable, Metastatic or Unresectable Locally Advanced Breast Cancer.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 420
- 试验地点
- 1
- 主要终点
- Progression free survival
研究概览
简要总结
An open randomized phase III study to compare 8 continuous cycles of chemotherapy with 8 cycles of intermittent (2 times 4 cycles) chemotherapy in first line treatment, in combination with bevacizumab, and second line treatment of patients with HER2/neu negative, incurable, metastatic or unresectable locally advanced breast cancer.
详细描述
The primary goal of this non-inferiority trial is to determine if the results obtained with a intermittent chemotherapy regimen (2 x 4 cycles of paclitaxel) are not inferior to the results of a continuous chemotherapy regimen (8 cycles of paclitaxel), both combined with bevacizumab in first line treatment of patients with HER2/neu negative, incurable, metastatic or unresectable locally advanced breast cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Female patients ≥ 18 years old.
- •Patients with HER2/neu negative, incurable, metastatic or unresectable locally advanced breast cancer, who are candidates for chemotherapy.
- •Patients with measurable or evaluable-only (RECIST 1.1)
- •Documented Estrogen Receptor (ER) / Progesteron Receptor (PR) status.
- •HER2/neu-negative disease
- •Patients with an ECOG Performance Status ≤
- •Life expectancy of > 12 weeks.
- •Signature of Informed Consent Form
排除标准
- •Previous chemotherapy for HER2/neu negative, incurable, metastatic or unresectable locally advanced breast cancer.
- •Prior hormonal therapy for HER2/neu negative, incurable, metastatic or unresectable locally advanced breast cancer that has not been discontinued 1 week before start of study treatment.
- •Prior adjuvant/neo-adjuvant chemotherapy within 6 months prior to first study treatment. However, if the prior adjuvant/neo-adjuvant chemotherapy was taxane based, patients are excluded if they received their last chemotherapy within12 months prior to first study treatment.
- •Prior radiotherapy covering more than 30% of marrow-bearing bone.
- •Patients that have received recent radiation therapy that are not recovered from any significant (Grade ≥ 3) acute toxicity prior to study treatment.
- •Prior therapy with bevacizumab, sorafenib, sunitinib, or other VEGF pathway-targeted therapy.
- •Chronic daily treatment with aspirin
- •Chronic daily treatment with corticosteroids, with the exception of inhaled steroids.
- •Current or recent treatment with another investigational drug or participation in another investigational study.
- •Inadequate bone marrow, liver, renal function
- •INR > 1.5 or an aPTT > 1.5 x ULN within 7 days prior to first study treatment.
- •Known CNS disease, except for treated brain metastases.
- •Patients with concurrent active malignancy
- •Pregnant or lactating
- •Women of childbearing potential not using effective, non-hormonal means of contraception
- •Major surgical procedure (including open biopsy) within 28 days prior to the first study treatment
- •Core biopsy or other minor surgical procedure, within 7 days prior to day
- •Significant vascular disease within 6 months prior to day
- •Any previous venous thrombo-embolism > CTC Grade
- •History of haemoptysis
- •History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding.
- •Uncontrolled hypertension
- •Clinically significant (i.e. active) cardiovasculair disease
- •LVEF by MUGA or ECHO < 50%.
- •History of abdominal fistula, Grade 4 bowel obstruction or GI perforation, intra-abdominal abscess within 6 months of randomization.
- •Serious non-healing wound, peptic ulcer or bone fracture.
- •Known hypersensitivity to any of the study drugs or excipients.
- •Hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies.
- •Psychiatric illness, physical examination or laboratory findings that may interfer with protocol
研究组 & 干预措施
8 cycles of Paclitaxel & bevacizumab
8 cycles of Paclitaxel: 90 mg/m2 IV on days 1, 8 and 15 every 28 days & Bevacizumab: 10 mg/kg IV on days 1 and 15 every 28 days
干预措施: Paclitaxel, Bevacizumab, liposomal doxorubicin, Capecitabine (Drug)
2 x 4 cycles of Paclitaxel & bevacizumab
intermittent 2x4 cycles of Paclitaxel: 90 mg/m2 IV on days 1, 8 and 15 every 28 days & Bevacizumab: 10 mg/kg IV on days 1 and 15 every 28 days
干预措施: Paclitaxel, Bevacizumab, liposomal doxorubicin, Capecitabine (Drug)
结局指标
主要结局
Progression free survival
时间窗: 1 year
PFS is defined as the time from start of treatment to the documented progression that requires the patient to switch to the next treatment line or to death due to any cause.
次要结局
- Duration of objective response(1 year)
- Progression free survival second line treatment(1 year)
- Objective overall response rate(1 year)
- Overall survival(1 year)
- Safety and tolerability. The total number of grade 3 and 4 adverse events will be analyzed.(1 year)
- Quality of life measures(1 year)
- Pharmacoeconomics(1 year)