Status:
COMPLETED
CESAR Study in Prostate Cancer With Temsirolimus Added to Standard Docetaxel Therapy (CEPTAS)
Lead Sponsor:
Central European Society for Anticancer Drug Research
Conditions:
Prostatic Neoplasms
Eligibility:
MALE
18+ years
Phase:
PHASE1
PHASE2
Brief Summary
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 ...
Detailed Description
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 I...
Eligibility Criteria
Inclusion
- 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).
Exclusion
Key Trial Info
Start Date :
July 1 2010
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
October 1 2015
Estimated Enrollment :
19 Patients enrolled
Trial Details
Trial ID
NCT01206036
Start Date
July 1 2010
End Date
October 1 2015
Last Update
January 27 2016
Active Locations (2)
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1
CESAR Study Center
Essen, Germany
2
CESAR Study Center
Freiburg im Breisgau, Germany