A Phase II Study of AZD2171 in Metastatic Androgen Independent Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 59
- 试验地点
- 1
- 主要终点
- Percent Probability of Participants With 6-month Progression-free Survival (PFS)
研究概览
简要总结
Background:
- AZD2171 (Cediranib) is an experimental drug that inhibits formation of new blood vessels.
- Tumors need new blood vessels to grow. Preventing the growth of new blood vessels with AZD2171 may inhibit tumor growth.
Objectives:
-To determine the effectiveness and side effects of AZD2171 in patients with prostate cancer that has metastasized (spread beyond the primary site).
Eligibility:
- Males 18 years of age and older with androgen-independent prostate cancer that has metastasized.
- Patients must have received prior treatment with docetaxel.
Design:
Patients take one AZD2171 by mouth every day in 28-day treatment cycles and undergo the following procedures:
- 1- to 2-day hospitalization at the start of the study for biopsies and blood measurements to determine the level of AZD2171 in the bloodstream. Blood is drawn immediately before the first dose, and 0.25 hr, 0.5 hr, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr, and 48 hours after the dose is taken.
- Blood tests before starting treatment and then monthly to determine the level of vascular endothelial growth factor receptor ( VEGFR), a protein involved in blood vessel formation.
- Magnetic resonance imaging (MRI) scans once a month to evaluate blood flow.
- Tumor biopsies (optional) both before and after the second and sixth treatment cycles.
- Clinic visits every 4 weeks, including various routine and research blood tests, urine test and electrocardiogram.
- Computed tomography (CT) scan of the chest, abdomen, and pelvis every 8 weeks
- Bone scan every 8 weeks
Patients record all doses of AZD2171 taken or missed in a pill diary. They record their blood pressure at least once daily in a blood pressure diary.
Treatment may continue as long as the patient tolerates the AZD2171 and the cancer does not worsen.
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详细描述
Background:
- AZD2171 (Cediranib) is an oral potent inhibitor of receptor tyrosine kinases which impact vascular endothelial growth factor-A (VEGF).
- VEGF appears important in blood vessel formation and disease progression in prostate cancer.
- No known effective therapy in patients with progressive androgen-independent prostate cancer after treatment with docetaxel.
Objectives:
- Primary objective of this study is to determine if AZD2171 is associated with a 30% 6 month probability of progression free survival in patients with metastatic androgen independent prostate cancer (AIPC) as determined by clinical and radiographic criteria.
- Secondary objective of this study will be demonstration of biologic effect by the drug in the patient and on the tumor (when possible). Correlative studies will be conducted on serially obtained tissue biopsies and white blood cell collections.
- Laboratory correlates will include elucidation of activation of components of the VEGFR2 and angiogenesis pathways and evaluation of endothelial cell adhesion molecules (released by damaged cells) using enzyme-linked immunosorbent assay (ELISA), pharmacogenetic analysis of kinase insert domain receptor (KDR) variants and single nucleotide polymorphisms, and pharmacokinetic characterization of AZD2171 activity.
Eligibility:
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
- Male
- 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
AZD2171 in Prostate Cancer
Cohort 1 (n=35) received 20 mg AZD2171 (Cediranib) orally daily. Cohort 2 (n=23) received prednisone 10 mg orally daily with 20 mg AZD2171.
干预措施: Magnetic Resonance Imaging (DCE-MRI) (Procedure)
AZD2171 in Prostate Cancer
Cohort 1 (n=35) received 20 mg AZD2171 (Cediranib) orally daily. Cohort 2 (n=23) received prednisone 10 mg orally daily with 20 mg AZD2171.
干预措施: AZD2171 (Drug)
AZD2171 in Prostate Cancer
Cohort 1 (n=35) received 20 mg AZD2171 (Cediranib) orally daily. Cohort 2 (n=23) received prednisone 10 mg orally daily with 20 mg AZD2171.
干预措施: Prednisone (Drug)
结局指标
主要结局
Percent Probability of Participants With 6-month Progression-free Survival (PFS)
时间窗: 6 months
PFS is the proportion of subjects who progress or die by 6 months after the start of the combined therapy. PFS is determined by prostatic specific antigen (PSA) consensus criteria and the Response Evaluation Criteria in Solid Tumors (RECIST). PSA consensus criteria is defined as PSA decline of \>/= 50% or PSA progression. RECIST is defined as the following: Complete response (CR) is disappearance of all target lesions; partial response (PR) is at least a 30% decline in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; and stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease ((PD) at least a 20% increase in the sum of the LD of target lesions, or the appearance of one or more lesions), taking as reference the smallest sum LD since the treatment started. Data is estimated and the probability of PFS as a function of time was determined using the Kaplan-Meier method.
次要结局
- Number of Participants With Adverse Events(Date treatment consent signed to date off study, approximately 61.5 months)
- Number of Grade 2 Toxicities(61.5 months)
- Number of Grade 3 Toxicities(61.5 months)
- Median Overall Survival(44 months)
- Median Progression Free Survival (PFS)(up to 14.9 months based on a Kaplan-Meier analysis.)
- Response Per the Response Evaluation Criteria in Solid Tumors (RECIST)(Every 2 cycles (approximately 56 days))
研究者
William Dahut Jr., M.D.
Principal Investigator
National Institutes of Health Clinical Center (CC)