Trial of Dasatinib (Sprycel®) in Subjects With Hormone-refractory Prostate Cancer

Exclusion Criteria

• •Subjects should have had no chemotherapy within 4 weeks of the start of treatment with dasatinib
• •Prior localized radiotherapy for metastatic disease is permitted, provided the treatment volume is less than25% of potential marrow space (the radiotherapy must have been completed 6 weeks prior to enrollment)
• •Systemic radiotherapy with samarium-153 must have been completed at least 2 months prior to enrollment (subjects may not have received prior strontium-89 \[Metastron\] therapy)
• •At least 6 weeks have elapsed from the last dose of cytotoxic or targeted therapeutics to the time of prescreening; if the subject has received a combination regimen of standard chemotherapy plus an investigational agent, a 6 week washout period is required
• •Subjects may not have received treatment with any kinase inhibitor
• •At least 2 months must have elapsed from time of dosing with vaccines to the time of prescreening
• •No malignancy, other than prostate cancer, that required radiotherapy or systemic treatment within the past 5 years
• •Subjects may not have any of the following: Clinical evidence of uncontrolled heart failure, myocardial infarction, or angina within the previous 6 months; prolonged QT interval Fridericia's (QTcF) \> 450msec; history of unstable ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation, or torsades de pointes); concomitant use of drugs known to cause torsades de pointes \[quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, erythromycins, clarithromycin, chlorpromazine, haloperidol, mesoridazine,thioridazine, pimozide, cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine\] (these agents must have been discontinued at least 7 days prior to starting dasatinib); subjects with hypokalemia or hypomagnesemia are excluded if the electrolyte anomaly cannot be corrected
• •Subjects may not be enrolled with any of the following: History of a significant bleeding disorder unrelated to cancer, including diagnosed congenital bleeding disorders (e.g., von Willebrand's disease), and diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies); GI bleeding from any cause within 3 months; Concomitant use of anticoagulants, except for low-dose warfarin (for prophylaxis to prevent catheter thrombosis) or heparin flushes (for IV lines), is prohibited (Note that chronic use of aspirin is prohibited)
• •Subjects must meet the following restrictions: Subjects may not have a concurrent medical condition which may increase the risk of toxicity, including pleural or pericardial effusion of any grade, or uncontrolled hypertension; Concomitant use of H2 blockers or proton pump inhibitors with dasatinib is not recommended (The use of antacids should be considered in place of H2 blockers or proton pump inhibitors in patients receiving dasatinib therapy); Patient must discontinue St. Johns Wort while receiving dasatinib therapy; Subjects must not use intravenous bisphosphonates during the first 8 weeks of dasatinib therapy due to risk of hypocalcemia; Subjects may not be receiving any restricted cytochrome P450 3A4 (CYP3A4) inhibitors (If the investigator feels that any of these agents should be given as uniquely useful for a clear diagnosis, the situation should be discussed with the Principal Investigator, and a clear monitoring program should be planned)
• •Subjects may not have evidence of untreated intracranial metastases, or untreated prostate cancer producing spinal cord compression