A Phase II Trial of RAD001 and Bicalutamide for Androgen Independent Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- Overall Response Rate
研究概览
简要总结
In the treatment of castration-resistant prostate cancer (CRPC), therapies will long response durations remain elusive as a result of the inherent ability of prostate cancer cells to develop iterative resistance. The goal of this study is to learn if the study drug RAD001 together with Bicalutamide can slow the growth of prostate cancer. The safety of the combination will also be studied.
详细描述
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
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: RAD001 (Drug)
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.
干预措施: Bicalutamide (Drug)
结局指标
主要结局
Overall Response Rate
时间窗: 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.
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.
次要结局
- Incidence of Grade 4 Treatment-Related Toxicity(Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort.)
- Incidence of Grade 1-3 Treatment-Related Mucositis Toxicity(Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort.)
- Incidence of Grade 1-3 Treatment-Related Rash Toxicity(Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort.)
- Incidence of Grade 1-3 Treatment-Related Fatigue Toxicity(Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort.)
- Time to Progression (TTP)(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.)
研究者
Mary-Ellen Taplin, MD
Principal Investigator
Dana-Farber Cancer Institute