A Phase II Trial to Evaluate the Efficacy and Safety of Bevacizumab in Combination With Capecitabine (Xeloda) in Frail Patients With Untreated Metastatic Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 45
- 试验地点
- 12
- 主要终点
- Time to Disease Progression
研究概览
简要总结
The purpose of this study is to evaluate the safety and effectiveness of the bevacizumab and capecitabine combination in frail patients with untreated metastatic colorectal cancer.
详细描述
The study will evaluate the tolerability, safety, and feasibility of combination bevacizumab and capecitabine in a small number of frail patients with metastatic colorectal cancer who have a compromised performance status. Preclinical studies suggest that the combination of chemotherapy and anti-angiogenic therapy offer an increased anti-tumor effect compared with either treatment alone.
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
- •Histologically or cytologically proven adenocarcinoma of the colon at first diagnosis
- •Stage IV disease, with at least one measurable lesion according to the RECIST criteria
- •Eastern Cooperative Oncology Group (ECOG) performance status 2
- •No prior chemotherapy for metastatic colorectal cancer
- •Prior adjuvant chemotherapy is permitted.
- •At least 28 days since prior surgery
- •If female of childbearing potential, pregnancy test is negative and willing to use effective contraception while on treatment and for at least 3 months thereafter.
- •Required laboratory values:
- •Absolute neutrophil count > 1.5 x 10^9/L
- •Hemoglobin > 9.0 g/dL
- •Platelet count > 100 x 10^9/L
- •Creatinine < 2.0 mg/dL
- •Total bilirubin < 1.5 x upper limit of normal (ULN) (Patients with documented Gilbert's syndrome are eligible.)
- •Alkaline phosphatase and AST/ALT within the following parameters. In determining eligibility, the more abnormal of the two values (AST or ALT) should be used:
- •Alkaline phosphate and AST/ALT < or = ULN
- •Alkaline phosphate > 1x but < or = 2.5x and AST/ALT < or = ULN
- •Alkaline phosphate > 2.5x but < or = 5x and AST/ALT < or = ULN
- •Alkaline phosphate < or = ULN and AST/ALT > 1x but < or = 1.5x
- •Alkaline phosphate > 1x but < or = 2.5 x and AST/ALT > 1x but < or = 1.5x
- •Alkaline phosphate < or = ULN and AST/ALT > 1x but < or = 2.5x
排除标准
- •Prior chemotherapy for metastatic colorectal cancer
- •Prior treatment with an anti-angiogenic agent
- •Concurrent therapy with any other non-protocol anti-cancer therapy
- •Current or prior history of central nervous system or brain metastases
- •Presence of neuropathy > grade 2 (NCI-Common Toxicity Criteria (CTC) version 3.0) at baseline
- •Presence of any non-healing wound, fracture, or ulcer, or the presence of clinically significant (> grade 2) peripheral vascular disease
- •History of any other malignancy within the past 5 years, with the exception of non-melanoma skin cancer or carcinoma-in-situ of the cervix
- •Clinically significant cardiovascular disease (e.g., blood pressure [BP] > 150/100, myocardial infarction or stroke within the past 6 months, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication
- •Active peptic ulcer disease, inflammatory bowel disease, or other gastrointestinal condition increasing the risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning therapy
- •Active infection requiring parenteral antimicrobials
- •The presence of any other medical or psychiatric disorder that, in the opinion of the treating physician, would contraindicate the use of the drugs in this protocol or place the subject at undue risk for treatment complications
- •Inability to comply with the study protocol or follow-up procedures
- •Pregnancy or lactation
- •A history of a severe hypersensitivity reaction to bevacizumab, or capecitabine or other drugs formulated with polysorbate
- •Evidence of bleeding diathesis or coagulopathy.
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of the need for a major surgical procedure during the course of the study; minor surgical procedure, fine needle aspiration or core biopsy within 7 days prior to Day 0
- •Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
- •Unstable angina
- •Urine protein creatinine ratio greater than or equal to
- •Therapeutic anticoagulation with oral anticoagulation medications, specifically coumarins
研究组 & 干预措施
Bevacizumab Plus Capecitabine
Bevacizumab 7.5 mg/kg every 3 weeks will be administered interavenously (IV) to the enrolled patients. Oral capecitabine 1000 mg/m^2 twice daily for 14 days followed by 7 days off every 21 days. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of patient consent.
干预措施: Capecitabine (Xeloda) (Drug)
Bevacizumab Plus Capecitabine
Bevacizumab 7.5 mg/kg every 3 weeks will be administered interavenously (IV) to the enrolled patients. Oral capecitabine 1000 mg/m^2 twice daily for 14 days followed by 7 days off every 21 days. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of patient consent.
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Time to Disease Progression
时间窗: 12 months
Progression Free Survival (PFS)- the interval from the date of enrollment to the first documented date of disease progression, death due to cancer, or the last date of a definitive assessment (not an unknown assessment) at which the patient is known to be progression-free. If there is an unknown assessment, then (a) if the next subsequent definitive assessment is complete response (CR), partial response (PR), or stable disease (SD), the patient is considered to be progression-free at the date of the subsequent definitive assessment and PFS is calculated as above; (b) if the next subsequent definitive assessment is progressive disease (PD), the patient is considered to be a failure at the time of the (earliest) assessment of unknown preceding the documented disease progression (i.e. PFS is back-dated to the date of the unknown assessment) and (c) if there is no subsequent definitive assessment, PFS for the patient is considered to be a censored observation at the date
Number of Subjects Requiring Dose Modifications
时间窗: 3 months
Number of Subjects that required Bevacizumab or Capecitabine dose modifications, delay, reduction or discontinuation due to adverse reactions.
次要结局
- Response Rates(every 21 days up to 12 months)
- Quality of Life of Patients(Baseline, Cycle 2, and End of Study)