NCT01206036已完成1 期
Phase I/II Study With Temsirolimus Versus no add-on in Patients With Castration Resistant Prostate Cancer (CRPC) Receiving First-line Docetaxel Chemotherapy
Central European Society for Anticancer Drug Research3 个研究点 分布在 1 个国家目标入组 19 人开始时间: 2010年7月1日最近更新:
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 19
- 试验地点
- 3
- 主要终点
- recommended dose
研究概览
简要总结
In this Phase I study safety of the combination of Docetaxel and Temsirolimus needs to be shown before the study can be expanded into a Phase II study to examine the activity of a safe combination of Temsirolimus and Docetaxel in a comparison with Docetaxel alone.
详细描述
The purpose of this Phase I study is to evaluate feasibility of dose levels DL1, DL2 and DL3 (which are combinations of Temsirolimus and Docetaxel) and defining a recommended dose (RD) for the Phase II part using these dose levels in a dose escalating scheme.
Secondary objectives are the collection of safety data on the dose levels used in this part.
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
- •Phase I Part:
- •Adult males ≥18 years of age.
- •Patients with CRPC defined as confirmed rise of PSA levels after orchiectomy or LHRH agonist based therapy.
- •Progressive disease, defined as PSA progression by confirmed rising PSA levels.
- •PSA at time of study entry ≥2ng/ml within 1 week prior to treatment (according to Scher 2008).
- •Bone metastasis and/or lymph node and/or visceral organ metastases allowed. Measurable and non measurable disease allowed.
- •Performance status (PS) 0-1 ECOG.
- •Signed written informed consent.
- •White blood cell count (WBC) ≥4x10^9/L with neutrophils ≥1.5x10^9/L, platelet count ≥100x10^9/L, hemoglobin ≥9g/dL.
- •Total bilirubin <=2 x upper limit of normal.
- •AST and ALT <=2.5 x upper limit of normal, or <=5 x upper limit of normal in case of liver metastases.
- •Serum creatinine <=1.5 x upper limit of normal or creatinine clearance > 60 ml/min.
- •Androgen ablation will have to be continued. Antiandrogens such as bicalutamide will have to be discontinued at least 4 weeks prior to the start of study treatment.
排除标准
- •Phase I Part:
- •Clinically symptomatic brain or meningeal metastasis.
- •Receiving known strong CYP3A4 isoenzyme inhibitors and/or inducers.
- •Any investigational drug within the 30 days before inclusion.
- •Not recovered from prior biopsy, surgery, traumatic injury, and/or radiation therapy, as judged by the investigator.
- •Nonhealing wound or ulcer.
- •Grade ≥ 3 hemorrhage within the past month.
- •Any condition / concomitant disease not allowing chemotherapy with docetaxel, prednisone and temsirolimus in the discretion of the treating physician, like: Renal insufficiency requiring dialyses; congestive heart failure or uncontrolled angina pectoris; prior myocardial infarction within 6 months of start of chemotherapy; uncontrolled severe hypertension (failure of diastolic blood pressure to fall below 90 mm Hg despite the use of ≥ 3 anti-hypertensive drugs) or arrhythmias; instable diabetes mellitus, ulceration from diabetes mellitus or other conditions not allowing high dose corticosteroids; effusions in pericardium, pleura or abdomen symptomatic and in need of being punctured.
- •Known hypersensitivity to any of the components in the temsirolimus infusion or other medical reasons for not being able to receive adequate premedication (antihistamine agents).
- •Legal incapacity or limited legal capacity
- •Medical or psychological conditions that would not permit the patient to
- •complete the study or sign informed consent.
- •Inclusion Criteria Phase II Part, Chemotherapy Period:
- •Adult males ≥ 18 years of age.
- •Patients with CRPC defined as confirmed rise of PSA levels after orchiectomy or LHRH agonist based therapy
- •Progressive disease, defined as PSA progression by confirmed rising PSA levels
- •PSA at time of study entry ≥ 2ng/ml within 1 week prior to treatment (according to Scher 2008).
- •Bone metastasis and/or lymph node and/or visceral organ metastases allowed. Measurable and non measurable disease allowed.
- •Performance status (PS) 0-1 ECOG.
- •Signed written informed consent.
- •White blood cell count (WBC) ≥4x10^9/L with neutrophils ≥1.5x10^9/L, platelet count ≥100x10^9/L, hemoglobin ≥9g/dL.
- •Total bilirubin <= 2 x upper limit of normal.
- •AST and ALT <=2.5 x upper limit of normal, or <=5 x upper limit of normal in case of liver metastases.
- •Serum creatinine <=1.5 x upper limit of normal or creatinine clearance >60 ml/min.
- •Androgen ablation will have to be continued. Antiandrogens such as bicalutamide will have to be discontinued at least 4 weeks prior to the start of study treatment.
- •Exclusion Criteria Phase II Part, Chemotherapy Period:
- •Prior Chemotherapy.
- •Clinically symptomatic brain or meningeal metastasis.
- •Receiving known strong CYP3A4 isoenzyme inhibitors and/or inducers.
- •Any investigational drug within the 30 days before inclusion.
- •Not recovered from prior biopsy, surgery, traumatic injury, and/or radiation therapy, as judged by the investigator.
- •Nonhealing wound or ulcer.
- •Grade ≥ 3 hemorrhage within the past month.
- •Any condition / concomitant disease not allowing chemotherapy with docetaxel, prednisone and temsirolimus in the discretion of the treating physician, like: Renal insufficiency requiring dialyses; congestive heart failure or uncontrolled angina pectoris; prior myocardial infarction within 6 months of start of chemotherapy; uncontrolled severe hypertension (failure of diastolic blood pressure to fall below 90 mm Hg despite the use of ≥ 3 anti-hypertensive drugs) or arrhythmias; instable diabetes mellitus, ulceration from diabetes mellitus or other conditions not allowing high dose corticosteroids; effusions in pericardium, pleura or abdomen symptomatic and in need of being punctured.
- •Known hypersensitivity to any of the components in the temsirolimus infusion or other medical reasons for not being able to receive adequate premedication (antihistamine agents).
- •Legal incapacity or limited legal capacity.
- •Medical or psychological conditions that would not permit the patient to complete the study or sign informed consent.
- •Inclusion Criteria Phase II Part, Maintenance Period:
- •Completed 8 cycles (up to 26 weeks) treatment in Arm A
- •White blood cell count (WBC) ≥4x10^9/L with neutrophils ≥1.5x10^9/L, platelet count ≥100x10^9/L, hemoglobin ≥9g/dL.
- •Total bilirubin <=2 x upper limit of normal.
- •AST and ALT <=2.5 x upper limit of normal, or <=5 x upper limit of normal in case of liver metastases.
- •Serum creatinine <=1.5 x upper limit of normal or creatinine clearance >60 ml/min.
- •General condition sufficient to allow therapy with temsirolimus.
- •Signed Informed Consent.
- •Exclusion Criteria Phase II Part, Maintenance Period:
- •Disease Progression in the first 8 cycles (up to 26 weeks).
结局指标
主要结局
recommended dose
时间窗: 10 months
Phase I Part: Primary endpoint is the Recommended Dose (RD) for the Phase II Part chosen between the three DLs based on the dose escalation scheme.
disease progression-free survival
时间窗: 24 months
Phase II Part: Primary endpoint is to evaluate the activity of the addition of Temsirolimus to standard treatment on the disease progression-free survival (DPFS Chemotherapy) in patients with castration resistant prostate cancer receiving first-line Docetaxel chemotherapy.
次要结局
- DPFS time(24 months)
- quality of life(24 months)
- safety as defined as occurence of treatment related adverse events(10 months)
- overall response(24 months)
- 1-year Disease-Progression Free Survival Rate(24 months)
- PSA(24 months)
- overall survival(24 months)
- TTP-PSA(24 months)
- toxicity based on treatment-related toxicities using CTCAE v4.0(24 months)
- Frequency of medication for pain(24 months)
研究者
研究点 (3)
Loading locations...
相似试验
已完成
1 期
Temsirolimus and Sorafenib in Advanced Hepatocellular CarcinomaHepatocellular CarcinomaNCT01008917University of California, San Francisco25
已完成
1 期
Temsirolimus, Irinotecan Hydrochloride, and Temozolomide in Treating Younger Patients With Relapsed or Refractory Solid TumorsUnspecified Childhood Solid Tumor, Protocol SpecificNCT01141244National Cancer Institute (NCI)72
已完成
1 期
Temsirolimus, Dexamethasone, Mitoxantrone Hydrochloride, Vincristine Sulfate, and Pegaspargase in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Non-Hodgkin LymphomaChildhood B Acute Lymphoblastic LeukemiaChildhood T Acute Lymphoblastic LeukemiaMature T-Cell and NK-Cell Non-Hodgkin LymphomaRecurrent Childhood Acute Lymphoblastic LeukemiaRecurrent Childhood Lymphoblastic LymphomaNCT01403415National Cancer Institute (NCI)13
已完成
1 期
Sorafenib and Temsirolimus in Treating Patients With Unresectable or Metastatic Solid TumorsUnspecified Adult Solid Tumor, Protocol SpecificNCT00255658National Cancer Institute (NCI)40
已完成
1 期
Docetaxel and Sirolimus in Patients With Advanced MalignanciesAdvanced CancerNCT01054313M.D. Anderson Cancer Center103