Phase II Trial of VEGF Trap in Patients With Previously Treated Metastatic Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 75
- 试验地点
- 1
- 主要终点
- Progression-free Survival (Bevacizumab- naïve Group)
研究概览
简要总结
This phase II trial is studying how well VEGF Trap works in treating patients with previously treated metastatic colorectal cancer. VEGF Trap may stop the growth of colorectal cancer by blocking blood flow to the tumor.
详细描述
PRIMARY OBJECTIVES:
I. Determine the response rate (complete and partial) in patients with previously treated metastatic colorectal cancer treated with VEGF Trap.
II. Determine the incidence of disease stabilization, in terms of 4-month progression-free survival, in patients treated with this drug.
SECONDARY OBJECTIVES:
I. Determine the median survival time of patients treated with this drug. II. Determine the 1-year survival rate and stable disease rate in patients treated with this drug.
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/cytologically confirmed metastatic colorectal metastatic cancer
- •measurable disease (at least 1 lesion accurately measured in at least 1 dimension (longest diameter) as>20mm with conventional techniques or as >10mm with spiral CT scan
- •>=4 weeks from major surgery
- •at least 1prior line of systemic therapy for metastatic disease. Prior treatment with anti-epidermal growth factor receptor inhibitors is allowed. Last dose >=4 weeks prior to randomization
- •Two cohorts: 1) bevacizumab naïveand; 2) bevacizumab treated
- •May have received prior thymidylate synthetase inhibitor concurrently with radiation as "radiation sensitizer". Last dose >=4 weeks prior to randomization
- •Prior radiation treatment >=4 weeks prior to randomization
- •Age>=18 years
- •Life expectancy >=3 months
- •ECOG<=2 (Karnofsky=60%)
- •leukocytes >3.0x10^9/L
- •absolute neutrophil count >1.5 x 10^9/L
- •platelets>75x10^9/L
- •INR <1.5 unless on warfarin
- •total bilirubin within 1.5xULN
- •AST/ALT≤2.5 X institution ULN
- •creatinine≤1.5xULN OR creatinine clearance >60mL/min/1.73m2 for patients with creatinine levels above1.5x institution limits
- •Urinalysis negative for protein OR 24h urine for protein <500 mg
- •full-dose anticoagulants with PT INR >1.5 eligible provided that: a) patient is therapeutic on stable dose of warfarin or low molecular weight heparin; b) patients on warfarin, the upper target for INR is <=3; c) no active bleeding/pathological condition carrying high bleeding risk
- •Eligibility of patients receiving medications known to affect activity/PK of VEGF Trap will be determined by PI
- •Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 6 months after completion of VEGF Trap therapy
- •Ability to understand/willingness to sign written informed consent
排除标准
- •chemotherapy/radiotherapy within 4 weeks (6 weeks for nitrosoureas/mitomycin C) prior to study entry
- •Other investigational agents concurrently
- •History of prior anti-angiogenic therapy other than bevacizumab
- •Evidence of CNS disease
- •Known hypersensitivity to Chinese hamster ovary cell products/other recombinant human antibodies, and patients with a history of allergic reactions attributed to compounds of similar chemical/biologic composition to other agents used in the study.
- •Serious/non-healing wound/ulcer/bone fracture
- •History of abdominal fistula/GI perforation/bowel obstruction/intraabdominal abscess within 28 days of treatment
- •major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 therapy
- •anticipation of need for major surgical procedures during study
- •core biopsy within 7 days prior to Day 1 therapy
- •Patients with clinically significant cardiovascular disease
- •Evidence of bleeding diathesis or coagulopathy
- •PT INR >1.5 unless the patient is on full-dose warfarin
- •Use of thrombolytic agents within 1 month of study initiation
- •Significant Proteinuria (>500mg/24h): Urine protein should be screened by random urinalysis for protein. If dipstick positive (>1+), 24-hour urine protein should be obtained and if >500mg/24 h, patient will be excluded.
- •Uncontrolled intercurrent illness including but not limited to ongoing or active infection or psychiatric illness/social situations that would limit compliance with study
- •Pregnant women
- •HIV-positive patients on combination antiretroviral therapy are ineligible because of potential for PK interactions with VEGF Trap
研究组 & 干预措施
Arm I
Patients receive VEGF Trap (aflibercept) IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
干预措施: aflibercept (Drug)
结局指标
主要结局
Progression-free Survival (Bevacizumab- naïve Group)
时间窗: 4 months
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions Kaplan-Meier method will be used.Progression-free survival (Bevacizumab- naïve group)
Objective Tumor Response (Defined as Partial or Complete Response as Defined by the RECIST Criteria)
时间窗: Up to 6 years
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions:Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions
Progression-free Survival (Bevacizumab-treated Group)
时间窗: 4 months
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions Kaplan-Meier method will be used. Progression-free survival (Bevacizumab-treated group)
次要结局
- Time to Progression(12 months)
- Objective Stable Disease Rate(Up to 6 years)
- Overall Survival (Bevacizumab-naïve Group)(12 months)
- Overall Survival (Prior Bevacizumab Treated Group)(12 months)
- Number of Participants With Response (Bevacizumab-naïve Group)(Up to 6 years)
- Overall Survival (Bevacizumab-treated Group)(12 months)
- Number of Participants With Response (Bevacizumab-treated Group)(Up to 6 years)