Sorafenib Plus Capecitabine Efficacy Assessment in Patients With Advanced Pre-treated Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 97
- 试验地点
- 7
- 主要终点
- Overall survival at 6 months fixed endpoint
研究概览
简要总结
Prospective non-randomized phase II study assessing the activity of the Capecitabine-Sorafenib combination by estimating overall survival of the study population at a fixed time point (6 months) and, as an exploratory analysis the overall survival of metabolic responders versus non-responders.
详细描述
Treatment doses :
Sorafenib 200mg in the morning,400mg in the evening; escalation to 400mg twice daily after 1 cycle Capecitabine 850mg/m2 twice daily Oral Days 1-14, weeks 1-2
Fluoro-Deoxy Glucose Positron Emitting Tomography (FDG-PET)imaging at baseline and after 17-21 days while on therapy.
Sample size justification/statistical analysis
Sample size has been estimated in order to be able to test the null hypothesis that the overall survival rate at 6 months is less than 30%. This hypothesis will be tested using a binomial distribution. The study should be able to reject the null hypothesis, using a 1-sided test with α = 0.025, with a power of 90% in case of a true overall survival ≥ 50% (rate at 6 months). The sample size required is 66 eligible patients (to be followed for 6 months minimum). Analysis will be done on all registered patients using an ITT approach on all eligible patients.
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
- •Participants must have histologically confirmed colorectal cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
- •All standard chemotherapy agents (fluoropyrimidines, irinotecan, and oxaliplatin) and monoclonal antibodies (bevacizumab, cetuximab, and panitumumab) are allowed as administered therapy before study entry. No more than two lines of treatment for metastatic or recurrent disease are allowed, except for patients with KRAS-wt tumors, for which third line with anti-EGFR agents is allowed.
- •Age over 18 years.
- •Life expectancy of greater than 12 weeks.
- •ECOG performance status ≤
- •Participants must have normal organ and marrow function as defined below:
- •Leukocytes > 3,000/mcL
- •Absolute neutrophil count > 1,500/mcL
- •Platelets > 100,000/mcL
- •total bilirubin within 2 × normal institutional limits
- •AST/ALT/PAKL levels < 5 × institutional upper limit of normal
- •creatinine within 2 × normal institutional limits or creatinine clearance > 35mL/min
- •Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- •Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
- •Participants who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- •Participants may not be receiving any other experimental agents.
- •Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib or capecitabine.
- •Bleeding diathesis, history of cardiovascular ischemic disease or cerebrovascular incident within the last six months, or major surgery within four weeks.
- •Uncontrolled concurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Pregnant women are excluded from this study because sorafenib and capecitabine are antitumor agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with sorafenib or capecitabine, breastfeeding should be discontinued if the mother is treated with sorafenib or capecitabine. These potential risks may also apply to other agents used in this study.
- •Uncontrolled Diabetes
- •FDG PET/CT negative lesions or non metabolically assessable lesions (to small <2cm) at the base line FDG PET/CT
- •Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.
研究组 & 干预措施
Capecitabine & Sorafenib
Sorafenib 200mg in the morning,400mg in the evening; escalation to 400mg twice daily after 1 cycle, Oral, Continuous dosing Capecitabine 850mg/m2 twice daily, Oral Days 1-14, weeks 1-2
干预措施: chemotherapy (Drug)
结局指标
主要结局
Overall survival at 6 months fixed endpoint
时间窗: 6 months
The 2 primary co-endpoints are : 1. To obtain a preliminary assessment about the activity of the combination by estimating overall survival of the study population at a fixed time point (6 months) 2. To compare as an exploratory analysis the overall survival of metabolic responders versus non-responders.
次要结局
- To describe the adverse reactions associated with the study regimen in the study population.(12 months)
- To estimate the Progression Free Survival (PFS) distribution of the study population(12 months)
- To determine the objective response rate of the study population as assessed by standard imaging(12 months)
- To determine the correlation of growth modulation index (GMI), defined as the time to progression under the study regimen over the time to progression un-der the latest prior regimen administered to the patient, with overall survival and progression-free(12 months)
- To determine the correlation of early metabolic response, as assessed by FDG-PET/CT immediately before the first and the second cycles of treatment with the study regimen, with overall survival, progression-free survival, and response.(12 months)