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

This is an interventional treatment trial for Prostatic Neoplasms focused on measuring castration, prostate cancer, castration resistant prostate cancer, PSA, Docetaxel, Temsirolimus, disease progression free survival, DPFS, dose escalation Read More

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).