A Phase I/II Study of RAD001 With Docetaxel in the Treatment of Metastatic, Androgen Independent Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 5
- 主要终点
- Number of Patients Free of Dose Limiting Toxicity
研究概览
简要总结
The purpose of this study is to evaluate the safety and optimal dose of RAD001 and docetaxel plus prednisone in men with hormone refractory, metastatic prostate cancer (Phase I).
Once an appropriate dose is reached, the purpose then will be to determine the response rate of docetaxel plus RAD001 (Phase II).
详细描述
- Patients will be designated into one of two groups based upon the results of a FDG-PET scan.
- A patient with a baseline positive scan will have serum drawn for baseline serum proteomics assessment then be treated with RAD001 daily for two weeks. On day 10-14, another FDG-PET scan and serum assessment will be performed. An optional bone marrow biopsy may also be done. On day 15, patients will enter the Phase I portion of the trial at the current enrolling dosage or if Phase I is completed patients will enter Phase II.
- A patient that does not have a positive scan will enter directly into the Phase I trial or Phase II depending on which trial is currently enrolling.
- Phase I trial patients will have weekly laboratory evaluations and clinical evaluation every three weeks.
- Phase II trial patients will have laboratory evaluations on day one and day eight and clinical evaluation every three weeks.
- The maximum duration of the trial is one year of therapy.
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
- •Adenocarcinoma of the prostate with radiographic evidence of metastatic disease.
- •Willingness to undergo a baseline tumor biopsy.
- •Castrate levels of testosterone (testosterone < 50 ng/dL) on androgen deprivation therapy (ADT) with evidence of progression on ADT. GnRH therapy will be continued for those on it at baseline
- •Patient must have suspected tumor in an area that is safe to biopsy.
- •Other prior hormonal interventions or experimental approaches are allowed. These therapies must have been discontinued for a minimum of 28 days with cancer progression.
- •Prior or concurrent use of bisphosphonates is allowed.
- •One prior non-taxane chemotherapy allowed
- •≥ 3 weeks since major surgery; ≥ 4 weeks since radiotherapy; ≥ 8 weeks since prior strontium-89 or samarium 153
- •Performance Status: ECOG 0 or 1
- •ANC > 1,500/_l; platelets > 100,000/_l; total Bilirubin < upper limit of normal; AST and ALT < 3 x upper limits of normal; creatinine < 1.5 x upper limits of normal; total fasting cholesterol < 350 mg/dl; total triglycerides < 300 mg/dl
排除标准
- •Ongoing oral steroid use. Patients with a history of oral steroid use are eligible as long as the steroids have been discontinued prior to study entry. Ongoing topical and/or inhaled steroid use is allowed.
- •Prior taxane chemotherapy
- •Prior mTOR inhibitors (RAD001, rapamycin, CCI-779)
- •Currently active second malignancy other than non-melanoma skin cancer.
- •Ongoing peripheral neuropathy of Grade 2
研究组 & 干预措施
RAD001 Followed by RAD001 + Docetaxel
RAD001 10 mg daily for 2 weeks, followed by RAD001 + Docetaxel at one of three doses: 5 mg RAD001 and docetaxel at 60 mg/m2, 10 mg RAD001 and docetaxel at 60 mg/m2, and 10 mg RAD001 and docetaxel at 70 mg/m2. RAD001 was given daily. Docetaxel was given every 3 weeks by intravenous infusion. Patients also received prednisone 5 mg by mouth twice daily.
干预措施: RAD001 (Drug)
RAD001 Followed by RAD001 + Docetaxel
RAD001 10 mg daily for 2 weeks, followed by RAD001 + Docetaxel at one of three doses: 5 mg RAD001 and docetaxel at 60 mg/m2, 10 mg RAD001 and docetaxel at 60 mg/m2, and 10 mg RAD001 and docetaxel at 70 mg/m2. RAD001 was given daily. Docetaxel was given every 3 weeks by intravenous infusion. Patients also received prednisone 5 mg by mouth twice daily.
干预措施: Docetaxel (Drug)
RAD001 Followed by RAD001 + Docetaxel
RAD001 10 mg daily for 2 weeks, followed by RAD001 + Docetaxel at one of three doses: 5 mg RAD001 and docetaxel at 60 mg/m2, 10 mg RAD001 and docetaxel at 60 mg/m2, and 10 mg RAD001 and docetaxel at 70 mg/m2. RAD001 was given daily. Docetaxel was given every 3 weeks by intravenous infusion. Patients also received prednisone 5 mg by mouth twice daily.
干预措施: Prednisone (Drug)
结局指标
主要结局
Number of Patients Free of Dose Limiting Toxicity
时间窗: 21 days
A dose limiting toxicity was defined as an adverse event or laboratory abnormality that occurs to patients on the Phase I portion of the trial, during the first 21 days following the first dose of RAD001/docetaxel during cycle 1, judged to be related to RAD001/docetaxel and meeting any of the following criteria: Hematologic Toxicity: CTCAE grade 4 neutropenia \> 7 days or any Grade 3 or 4 neutropenia with fever Or CTCAE grade 3 or 4 thrombocytopenia \> 7 days Non-hematologic toxicity: The occurrence of non-hematologic CTCAE grade 3 or 4 adverse events will be considered dose limiting, except for the following: 1. CTCAE grade 3 nausea or grade 3 or 4 vomiting CTCAE grade 3 or 4 vomiting will only be considered dose limiting if it occurs despite the use of standard anti-emetics. 2. CTCAE grade 3 or 4 fever identified with a source (i.e. infection, tumor) 3. CTCAE grade 3 or 4 alkaline phosphatase.
次要结局
- Response Based on PET Scan(10 to 14 days after study entry)
研究者
Mary-Ellen Taplin, MD
Associate Professor of Medicine, HMS
Dana-Farber Cancer Institute