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

• Status: Completed
• Trial end date: 2015-10-01
• Target enrollment: 0
• Participant gender: Male

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 Temsirolimus and Docetaxel in a comparison with Docetaxel alone.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Central European Society for Anticancer Drug Research
• Treatments: Docetaxel; Everolimus; Sirolimus

Criteria

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).