A Phase I/II Study of Capecitabine/Oxaliplatin (XELOX) in Combination With Bevacizumab and Imatinib as First-line Treatment of Patients With Stage IV Colorectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 51
- 试验地点
- 8
- 主要终点
- Dose limiting toxicity.
研究概览
简要总结
Assessment of safety and toxicity, definition of the dose limiting toxicity (DLT) of the combination therapy consisting of Capecitabine, Oxaliplatin, Bevacizumab and Imatinib.
详细描述
The monoclonal anti-VEGF antibody bevacizumab has been approved for the treatment of stage IV colorectal cancer. The tyrosine kinase inhibitor imatinib mesylate has been shown to efficiently target PDGF-signalling. Blocking PDGFR-signalling leads to disruption of pericytes from the endothelium and reverses the maturation status thereby enhancing the sensitivity to anti-VEGF therapy.This background forms a rationale for a combined therapeutic PDGF and VEGF inhibition. Since bevacizumab shows best activity when used in combination with chemotherapy, capecitabine and oxaliplatin are included in this protocol. Patients with stage IV colorectal cancer and no prior chemotherapy can enter the study. Patients receive oral imatinib once a day on days 1-21. Oral Capecitabine is given on days 1-14 bid, Oxaliplatin and Bevacizumab are given on day 1. Courses are repeated every 22 days in the absence of disease progression or unacceptable toxicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically proven inoperable colorectal cancer
- •Adult patients >= 18 years of age
排除标准
- •Preceding chemo- or immunotherapy with the exception of adjuvant or neoadjuvant treatment of non-metastatic disease ending ≥ 6 month prior to study inclusion. Progression within 6 month after the end of adjuvant therapy must be excluded.
- •Other malignancies with the exception of basal cell carcinoma or successfully treated carcinoma in situ of the cervix uteri.
- •No history of severe comorbidities, i. e. uncontrolled hypertension, GI-bleeding, congestive heart-failure NYHA class II-IV, symptomatic coronary heart disease, myocardial infarction within 1 year prior to study inclusion, serious cardiac arrhythmias requiring medication, Grade II or greater peripheral vascular disease and other severe uncontrolled co-morbidities
- •No history of stroke or other CNS-diseases (tumors, seizure, transient ischemic attack etc.)
- •≥ Grade II peripheral artery vascular occlusive disease
- •Preexisting neuropathy ≥ Grade 1
- •Interstitial pneumonia or lung fibrosis
- •Serious, nonhealing wound, ulcer, or bone fracture
- •Preceding irradiation an indicator lesion except for documented progressive disease during irradiation and termination of irradiation ≥ 4 weeks from study inclusion
- •Thromboembolic or bleeding events within the last 6 month
- •Need for therapeutic anticoagulation (heparin, cumarin)
- •Use of ASS > 325 mg/die or NSAR
- •Proteinuria > 1+ (stix) as long as urine protein >1g/24h
研究组 & 干预措施
XELOX, Bevacizumab, Imatinib
干预措施: Oxaliplatin, Capecitabine, Bevacizumab, Imatinib (Drug)
结局指标
主要结局
Dose limiting toxicity.
时间窗: 6 weeks
次要结局
- Assessment of overall response rate and progression free survival.(6 month)
研究者
Ulrich Hacker
PD Dr.
University of Cologne