CESAR Study in Prostate Cancer With Temsirolimus Added to Standard Docetaxel Therapy (CEPTAS)

Inclusion Criteria 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. Exclusion Criteria 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).