Phase II Trial of Abraxane in Front Line Therapy of Hormone Refractory Metastatic Prostate Cancer
研究概览
详细说明
Taxanes are the most widely tested and effective chemotherapy drugs for hormone refractory prostate cancer. Weekly paclitaxel was reported to produce 25-39% PSA responses in first line and up to 33% in second line chemotherapy of patients with prostate cancer in early clinical trials (1, 2). Paclitaxel activity in prostate cancer is schedule dependent, and weekly paclitaxel was reported to produce highest response rates (1, 2). Docetaxel was recently approved by the Food and Drug Administration for treatment of hormone refractory metastatic prostate cancer, since it is the only chemotherapy drug with documented improvement in survival in this group of patients. Docetaxel was associated with 45.8% overall grade 3/4 toxicities and it has to be given with steroid pre-medication. This regimen might be difficult to use in advanced prostate cancer patients that are often elderly and with multiple co-morbid conditions.
ABI-007 [Abraxane™ (paclitaxel protein-bound particles for injectable suspension) (albumin-bound)] is the first in its class of biologically interactive albumin-bound forms of chemotherapy (3). This composition provides a novel approach of increasing intra-tumoral concentration of the drug by a receptor-mediated transport process allowing transcytosis across the endothelial cell wall, thereby breaching the blood/tumor interface. This albumin-specific receptor mediated process involves the binding of a specific receptor (gp60) on the endothelial cell wall, resulting in activation of a protein caveolin-1, which initiates an opening in the endothelial wall with formation of a little caves or caveolae, with transport of the albumin-bound chemotherapeutic complex via these caveolae to the underlying tumor interstitium (4). A protein specifically secreted by the tumor (SPARC) binds and entraps the albumin, allowing release of the hydrophobic drug to the tumor cell membrane. ABI-007 is the first biologically interactive albumin-bound chemotherapy agent leveraging this gp-60/caveolin-1/caveolae/Sparc pathway to increase intra-tumoral concentration of the drug and reduce the amount of the toxic chemotherapy in normal tissue.
Preclinical studies comparing Abraxane to paclitaxel demonstrated lower toxicities, with a maximum tolerated dose (MTD) approximately 50% higher for Abraxane (7) compared to paclitaxel (11). At equal doses there was less myelosuppression and improved efficacy than paclitaxel in a xenograft tumor model of human mammary adenocarcinoma. Clinical studies confirmed improved toxicity profile and higher response rates, in metastatic breast cancer, of Abraxane compared to cremophor EL paclitaxel (Taxol) (5, 8). The weekly regimen was shown to be active even in patients with cancers refractory to paclitaxel, docetaxel or when Abraxane was given after both agents (8).
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
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California
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Vallejo、California、美国、94589
- Kaiser Permanente
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Histopathologically or cytologically proven adenocarcinoma of the prostate metastatic to the bones or lymph nodes as documented by bone scan or CT scan with evidence of progression despite standard hormonal management (orchiectomy, GNRH agonist, or GNRH antagonist-hormone refractory). No major organ allowed
- No prior chemotherapy
- For patients who have been on anti-androgen therapy, patients must have progressive disease after anti-androgen withdrawal (6 weeks biclutamide or nilutamide, 4 weeks for flutamide).
- PSA progression is defined as rising PSA.
Exclusion Criteria:
- Active malignancy other than non-melanoma skin cancer within 5 years of enrollment.
- Significant active medical illness which in the opinion of the investigator will preclude treatment.
- Brain metastasis, any non-bone metastasis except lymph node metastasis
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:ABI-007
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This is a Phase II single-arm study for first-line chemotherapy of patients with hormone refractory metastatic prostate cancer.
Eligible patients will be chemotherapy naive and will receive weekly Abraxane 100mg/m2 IV over 30 minutes.
These will be 4-week cycles with patients receiving Abraxane 100 mg/m2 weekly for 3 weeks and one week off for rest.
Patients will continue on therapy until disease or PSA
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研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
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Evaluate the efficacy of Abraxane in first line chemotherapy of patients with
大体时间:August 2008
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August 2008
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hormone refractory metastatic prostate cancer, based on prostate specific antigen (PSA) response
大体时间:August 2008
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August 2008
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次要结果测量
结果测量 |
大体时间 |
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Evaluate the effect of Abraxane on,Time to PSA progression, Measurable tumor response rate (if measureable disease at baseline), Overall survival
大体时间:August 2008
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August 2008
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Evaluate the toxicity of Abraxane in this group of patients.
大体时间:August 2008
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August 2008
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合作者和调查者
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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Abraxane的临床试验
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University of Alabama at BirminghamSusan G. Komen Breast Cancer Foundation; Daiichi Sankyo UK Ltd.; Triple Negative Breast Cancer...完全的
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Southeastern Gynecologic OncologyCelgene Corporation完全的
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University Health Network, TorontoCelgene Corporation完全的