Phase II Study of Sorafenib/Avastin® as Salvage Therapy in Patients With Metastatic Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 83
- 试验地点
- 210
- 主要终点
- Progression-free Survival Rate
研究概览
简要总结
This phase II trial is studying how well giving sorafenib together with bevacizumab works in treating patients with metastatic colorectal cancer. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Sorafenib and bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving sorafenib together with bevacizumab may kill more tumor cells
详细描述
PRIMARY OBJECTIVES:
I. Evaluate proportion of patients who are progression-free at 3 months (in historic comparison with results for single-agent bevacizumab in ECOG 3200).
SECONDARY OBJECTIVES:
I. Response rate (RR) II. Overall survival (OS) III. Safety IV. Feasibility
OUTLINE: This is a multicenter study.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of stage IV colorectal cancer (histologic proof is not required)
- •Measurable disease
- •Spiral CT scan required for both pre- and post-treatment tumor assessments of lesions measuring 1-2 cm
- •Progressive disease during or within 6 months of most recent prior chemotherapy regimen (bevacizumab, fluoropyrimidine, oxaliplatin, or irinotecan-based treatment) OR considered ineligible for standard therapy
- •Documentation of submission of tumor material for Kirsten Rat Sarcoma (KRAS) testing available
- •Prior anti-epidermal growth factor receptor (EGFR) antibody therapy (e.g., cetuximab or panitumumab) required for patients with wild-type KRAS tumor
- •No known brain metastasis
- •Patients with neurological symptoms must undergo a CT scan or MRI of the brain to exclude brain metastasis
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Life expectancy ≥ 6 months
- •Hemoglobin ≥ 9.0 g/dL
- •Absolute neutrophil count (ANC) ≥ 1,500/mm³
- •Platelet count ≥ 100,000/mm³
- •White blood cell count (WBC) ≥ 3,400/mm³
- •International normalized ratio (INR) < 1.5 (≤ 3.0 if on anti-coagulation therapy [e.g., warfarin or heparin])
- •Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) ≤ 2.5 times ULN (≤ 5 times ULN if there is liver involvement)
- •Alkaline phosphatase ≤ 3 times ULN
- •Creatinine ≤ 1.5 times ULN
- •Urine protein:creatinine ratio < 1 OR urine dipstick < 2+ OR urine protein < 1,000 mg by 24-hour urine collection
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment (≥ 2 weeks after completion of treatment with sorafenib tosylate alone)
- •Willing to provide mandatory blood samples for translational research studies
- •Able to swallow whole pills
- •No inadequately controlled hypertension (i.e., systolic BP > 150 mm Hg or diastolic BP > 100 mm Hg on anti-hypertensive medications)
- •No prior hypertensive crisis or hypertensive encephalopathy
- •No myocardial infarction or unstable angina within the past 6 months
- •No congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
- •No thrombolic or embolic events (e.g., cerebrovascular accident, including transient ischemic attacks) within the past 6 months
- •No hemorrhage or bleeding event > grade 3 within the past 4 weeks
- •No evidence or history of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)
- •No greater than normal risk of bleeding
- •No active or recent hemoptysis (≥ ½ teaspoon of bright red blood per episode) within the past 30 days
- •No concurrent uncontrolled illness including, but not limited to, any of the following:
- •Ongoing or active infection
- •Symptomatic congestive heart failure
- •Unstable angina pectoris
- •Cardiac arrhythmia requiring anti-arrhythmic drugs
- •Psychiatric illness or social situations that would limit compliance with study requirements
- •No known HIV infection or chronic hepatitis B or C infection
- •No serious, non-healing wound, active ulcer, or untreated bone fracture
- •Patients with fractures secondary to metastatic disease are eligible after appropriate radiotherapy
- •No significant traumatic injury within the past 4 weeks
- •No known or suspected allergy or hypersensitivity to any component of bevacizumab, sorafenib tosylate, or their excipients or to any other agent given in the course of this study
- •No malabsorption problem
- •None of the following within the past 6 months:
- •Significant vascular disease (e.g., aortic aneurysm or aortic dissection)
- •Peripheral arterial thrombosis
- •Symptomatic peripheral vascular disease
- 另有 14 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (sorafenib tosylate and bevacizumab)
Patients receive sorafenib tosylate orally twice daily on days 1-5 and 8-12 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Blood samples are collected at baseline and then periodically during study treatment for laboratory biomarker and pharmacogenetic studies
干预措施: sorafenib tosylate (Drug)
Treatment (sorafenib tosylate and bevacizumab)
Patients receive sorafenib tosylate orally twice daily on days 1-5 and 8-12 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Blood samples are collected at baseline and then periodically during study treatment for laboratory biomarker and pharmacogenetic studies
干预措施: bevacizumab (Biological)
结局指标
主要结局
Progression-free Survival Rate
时间窗: At 3 months
The primary endpoint of this trial is progression free survival at 3 months. All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be considered evaluable. Patients lost to follow-up before 3 months (e.g., progression, refusing further treatment, etc.) will be considered treatment failures. All eligible patients will be followed until death or a minimum of 3 years. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Progression is defined as at least a 20% increase in the sum of longest liameter of target lesions taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.
次要结局
- Response Rate(Up to 2 years)
- Overall Survival(Time from registration to death, assessed up to 2 years)
- Feasibility of Study Treatment(Up to 2 years)