A Phase I study of the mTOR inhibitor Temsirolimus in combination with the HDAC inhibitor Vorinostat in patients with metastatic prostate cancer .
To determine safety, tolerability and recommended Phase II dose of Temsirolimus in combination with Vorinostat in metastatic, hormone refractory, chemo-resistant prostate cancer.
Patients must have a histologically confirmed diagnosis of adenocarcinoma of the prostate that is hormone refractory and with evidence of progressive metastatic disease following docetaxel treatment by any of the following: 1. Increased serum prostate-specific antigen (PSA) levels confirmed by 3 consecutive PSA measurements (at least 2 weeks apart), the first sample to be taken at least 6 weeks after bicalutamide or megestrol acetate withdrawal AND/OR 2. Progression of bidimensionally measurable soft tissue (nodal) metastasis by CT scan or MRI within the past 4 weeks AND/OR 3. Progression of bone disease by at least two new bone lesions on bone scan confirmed by a second bone scan
Eligible patients will be assigned to the starting dose of 200 mg QD for Vorinostat and 15 mg IV of Temsirolimus weekly. Subsequent Vorinostat and Temsirolimus dose escalated levels will be comprised of 2 patients per cohorts and will be selected from five pre-specified combinations of Vorinostat and Temsirolimus as determined by the CRM (Continual Reassessment Method).
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