RAD001 and Bicalutamide for Androgen Independent Prostate Cancer
A Phase II Trial of RAD001 and Bicalutamide for Androgen Independent Prostate Cancer
研究概览
详细说明
Bicalutamide, an androgen receptor (AR) antagonist, is frequently used as the first 'secondary hormonal therapy' in combination with another established agent (LHRH: luteinizing hormone-releasing hormone agonist/antagonist) to treat CRPC. A series of studies have shown that RAD001 through inhibition of mammalian target of rapamycin (mTOR) pathway has antitumor and anti-angiogenic activities. The hypothesis is that the combination of an antiandrogen and mTOR inhibitor would have additive and clinically significant effects in CRPC.
STATISTICAL CONSIDERATIONS:
The regimen will be considered promising if the rate of response/favorable outcome is 40% or greater. A rate of 20% (similar to that observed for bicalutamide alone) will not be considered worthy of further study. 38 patients (of whom 36 are assumed to be eligible) will be accrued to the study. If 11 or more patients have a favorable outcome (stable disease > 6 months or response), the combination will be considered worthy of further study. Given this design, there is a 9% probability of declaring the combination effective if the true favorable outcome rate is 20% and a 91% probability of declaring the combination effective if the true favorable outcome rate is 40%.
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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Massachusetts
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Boston、Massachusetts、美国、02115
- Dana-Farber Cancer Institute
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Boston、Massachusetts、美国、02115
- Beth Israel Deaconess Medical Center
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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:
- 18 years of age or older
- Histologically documented prostate cancer
- Castration resistant prostate cancer defined as two rising PSAs on castration therapy
- Baseline PSA of 2ns/mL or greater
- Testosterone of 50ng/mL or less
- Patients on LHRH agonist/antagonist must continue therapy at the recommended dosing intervals
- Prior bicalutamide is allowed as long as treatment was for 6 months or longer
- Metastatic disease is not required
- Minimum of four weeks since any major surgery, completion of radiation, or completion of all prior systemic anticancer therapy
- ECOG Performance Status equal to or less than 2
- Adequate bone marrow and liver function as outlined by parameters in the protocol
Exclusion Criteria:
- Prior treatment with any investigational drug within the preceding 4 weeks
- Prior treatment with an mTOR inhibitor
- Fasting lipids over the parameters outlined in the protocol
- Chronic treatment with systemic steroids or another immunosuppressive agent
- Patients should not receive immunization with attenuated live vaccines during study period or within one week of study entry
- Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
- Other malignancies within the past 3 years except for adequately treated or basal squamous cell carcinomas of the skin
- Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
- Known history of HIV seropositivity
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001
- Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumarin)
- Men able to conceive and unwilling to practice an effective method of birth control
- Known hypersensitivity to RAD001 or other rapamycins or to its excipients
- History of noncompliance to medical regimens
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：RAD001 + Bicalutamide
RAD001: once daily dose of 10 mg (5 mg tablets) Bicalutamide: once daily dose of 50 mg (50 mg tablets) 1 cycle=28 days Both agents are administered continuously until progression of disease or unacceptable toxicity. |
其他名称：
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Overall Response Rate
大体时间：PSA was measured monthly and measurable disease on imaging assessed every 2 cycles in first 8 weeks and every 3 cycles thereafter. In this study cohort, patients were followed on treatment up to approximately 1 year.
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Overall response rate is the percentage of patients achieving response taking into consideration measurable disease, bone metastases, and PSA. PSA declines in the absence of both measurable disease and the appearance of new bone lesions or a response in measurable disease without an increase in PSA or the appearance of new bone lesions. Patients with stable disease (SD) lasting at least 6 months will also be considered responders. Per RECIST guidelines, for target lesions, complete response (CR) is complete disappearance of all target lesions and partial response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. CR or PR confirmation is required within 4 weeks. Per modified PSAWG2 criteria (Scher H, Halabi S, Tannock I et al. JCO 2008) PSA response is defined as PSA decline ≥ 50% from baseline confirmed by a second measurement at least 4 weeks later. |
PSA was measured monthly and measurable disease on imaging assessed every 2 cycles in first 8 weeks and every 3 cycles thereafter. In this study cohort, patients were followed on treatment up to approximately 1 year.
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Incidence of Grade 4 Treatment-Related Toxicity
大体时间：Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort.
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All grade 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv3 as reported on case report forms were counted.
Incidence is the number of patients experiencing at least one treatment-related grade 4 AE of any type during the time of observation.
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Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort.
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Incidence of Grade 1-3 Treatment-Related Mucositis Toxicity
大体时间：Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort.
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All grade 1-3 mucositis adverse events (AE) with treatment attribution of possible, probable or definite based on CTCAEv3 as reported on case report forms were counted.
Incidence is the number of patients experiencing at least one treatment-related grade 1-3 mucositis AE during the time of observation.
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Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort.
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Incidence of Grade 1-3 Treatment-Related Rash Toxicity
大体时间：Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort.
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All grade 1-3 rash adverse events (AE) with treatment attribution of possible, probable or definite based on CTCAEv3 as reported on case report forms were counted.
Incidence is the number of patients experiencing at least one treatment-related grade 1-3 rash AE during the time of observation.
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Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort.
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Incidence of Grade 1-3 Treatment-Related Fatigue Toxicity
大体时间：Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort.
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All grade 1-3 fatigue adverse events (AE) with treatment attribution of possible, probable or definite based on CTCAEv3 as reported on case report forms were counted.
Incidence is the number of patients experiencing at least one treatment-related grade 1-3 fatigue AE during the time of observation.
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Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort.
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Time to Progression (TTP)
大体时间：PSA was measured monthly and measurable disease on imaging assessed every 2 cycles in first 8 weeks and every 3 cycles thereafter. In this study cohort, patients were followed on treatment up to approximately 1 year.
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TTP estimated with Kaplan-Meier methods is defined as the time from treatment start to when PSA progression criteria is first met, or the date of measurable or non-measurable disease progression (PD).
Absent progression, patients are censored at the date of the last PSA measurement.
PSA progression is a ≥25% increase over baseline or nadir PSA, whichever is lowest with a minimum increase of 5 ng/mL.
If PSA declines ≥50%, PSA progression is a ≥50% PSA increase above nadir with a minimum increase of 5 ng/mL or back to pretreatment baseline, whichever is lowest.
PSA progression requires 2 week confirmation.
Per RECIST, PD is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or appearance of new lesions.
Non-measurable PD is defined as a worsening bone scan, as indicated by the appearance of two or more new lesions, the appearance of new non-bony metastases or a requirement for radiation therapy.
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PSA was measured monthly and measurable disease on imaging assessed every 2 cycles in first 8 weeks and every 3 cycles thereafter. In this study cohort, patients were followed on treatment up to approximately 1 year.
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合作者和调查者
调查人员
- 学习椅：Mary-Ellen Taplin, MD、Dana-Farber Cancer Institute
出版物和有用的链接
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 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
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