A Phase II Trial of Bevacizumab and Irinotecan for Patients With Recurrent High-Grade Gliomas Immediately Following Tumor Progression After Treatment w/Bevacizumab Alone: A Companion Trial to NCI Study 06-C-0064 (NCT00271609)(Bevacizumab Alone for Recurrent Gliomas)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Radiographic Response Rate (Malignant Glioma Participants)
研究概览
简要总结
Background:
- Bevacizumab is a genetically engineered antibody that blocks the growth of new blood vessels in tumors. It has shown activity against human brain tumors in laboratory tests and human clinical trials.
- Irinotecan causes damage to the deoxyribonucleic acid (DNA) in cancer cells so that the cells cannot reproduce or repair themselves. It is approved for treating patients with colorectal cancer.
- Bevacizumab and irinotecan in combination are more effective against colon cancer than either drug alone.
Objectives:
- To determine the safety of bevacizumab and irinotecan and any side effects associated with the combination of the two drugs when given to patients with high grade gliomas.
- To determine if the combination of bevacizumab and irinotecan can help patients with brain tumors that have grown after treatment with bevacizumab alone.
Eligibility:
-Patients 18 years of age and older who have been treated on National Cancer Institute (NCI) trial 06-C-0064 (NCT00271609), "Bevacizumab Alone for Recurrent Gliomas," and whose tumor has progressed.
Design:
Participants receive infusions of bevacizumab and irinotecan through a vein once every 2 weeks in 4-week treatment cycles, plus the following procedures:
- History, physical and neurological examinations every 2 weeks for the first treatment cycle and then every 4 weeks
- Magnetic Resonance Imaging (MRI) scan of the head every 4 weeks.
- Routine lab every week.
- Quality-of-life questionnaire every 4 weeks
详细描述
Background:
- Bevacizumab is a humanized IgG1 monoclonal antibody (MAb) that binds all biologically active isoforms of human vascular endothelial growth factor (VEGF, or VEGF-A) with high affinity (kd = 1.1 nM ). The antibody consists of a human IgG1 framework and the antigen-binding complementarity-determining regions from the murine anti-VEGF MAb A.4.6.1.
- Irinotecan is a semisynthetic derivative of camptothecin that possesses greater aqueous solubility, greater in vitro and in vivo activity, and is associated with less severe and more predictable toxicity than camptothecin.
- We now propose treating patients whose tumors progress on our bevacizumab alone protocol with the combination of bevacizumab with irinotecan. We believe that this trial design has significant power to detect a true synergistic effect between the two agents given that the single agent activity of irinotecan is so low in patients with recurrent malignant gliomas (2-5% response rate) and the patients being treated on this trial will have tumors that have already progressed through bevacizumab.
Objective:
- To establish data and safety regarding the anti-tumor activity of bevacizumab plus irinotecan in patients with recurrent high-grade gliomas that have progressed on bevacizumab alone as determined by objective radiographic response rate.
- To determine the 6 month progression-free survival of treated patients and to characterize the pattern of changes in the number of endothelial progenitor cells over time and across patients.
- To obtain preliminary data regarding how response to treatment (stable disease or radiographic response) effects monthly measurements of quality of life while on study.
Eligibility:
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Bevacizumab & Irinotecan Patients
Bevacizumab - 10 mg/kg intravenous injection Irinotecan - 125 mg/m^2 if patient is on a non-enzyme inducing anti-epileptic drugs 340 mg/m^2 if patient is on enzyme inducing anti-epileptic drugs every two weeks on a 4 week cycle
干预措施: Bevacizumab (Biological)
Bevacizumab & Irinotecan Patients
Bevacizumab - 10 mg/kg intravenous injection Irinotecan - 125 mg/m^2 if patient is on a non-enzyme inducing anti-epileptic drugs 340 mg/m^2 if patient is on enzyme inducing anti-epileptic drugs every two weeks on a 4 week cycle
干预措施: Irinotecan hydrochloride (Drug)
结局指标
主要结局
Radiographic Response Rate (Malignant Glioma Participants)
时间窗: 23 months (date of first enrollment to 1 month after last progression)
Definition of response: complete response (CR) is the complete disappearance of all measurable and evaluable disease. Partial response (PR) is greater than or equal to a 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable lesions. Stable/No response (SD, NR)does not qualify for CR, PR, or progression. Progression is a 25% increase in the sum of products of all measurable lesions (or two target lesions if too numerous over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline.
Number of Participants With Toxicity as Measured by The National Cancer Institute (NCI) Common Toxicity Criteria v. 3.0.
时间窗: 23 months (date of first enrollment to 1 month after last progression)
Here is the number of participants with any toxicity, defined as any adverse events possibly, probably or definitely related to the investigational drugs. For the detailed list of investigational new drug (IND)-related toxicities and other serious adverse events, see the adverse event module.
Radiographic Response Rate (Anaplastic Glioma Participants)
时间窗: 23 months (date of first enrollment to 1 month after last progression)
Definition of response: complete response (CR) is the complete disappearance of all measurable and evaluable disease. Partial response (PR) is greater than or equal to a 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable lesions. Stable/No response (SD, NR)does not qualify for CR, PR, or progression. Progression is a 25% increase in the sum of products of all measurable lesions (or two target lesions if too numerous over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline.
Radiographic Response Rate (Glioblastoma Multiforme Participants)
时间窗: 23 months (date of first enrollment to 1 month after last progression)
Definition of response: complete response (CR) is the complete disappearance of all measurable and evaluable disease. Partial response (PR) is greater than or equal to a 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable lesions. Stable/No response (SD, NR)does not qualify for CR, PR, or progression. Progression is a 25% increase in the sum of products of all measurable lesions (or two target lesions if too numerous over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline.
次要结局
未报告次要终点