LDE225 + Docetaxel/Prednisone for Adv/Met Castrate Resistant Prostate Cancer w/ Disease Progression After Docetaxel

Exclusion Criteria

• •Asymptomatic or minimally symptomatic patients with docetaxel naïve metastatic castration resistant prostate cancer
• •Patients who have had major surgery within 4 weeks of initiation of study medication
• •Patients with concurrent uncontrolled medical conditions that may interfere with their participation in the study or potentially affect the interpretation of the study data
• •Patients unable to take oral drugs or with lack of physical integrity of the upper gastrointestinal tract or known malabsorption syndromes (e.g., ulcerative colitis, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
• •Patients who have previously been treated with systemic LDE225 or with other Hh pathway inhibitors
• •Patients who have active uncontrolled or symptomatic central nervous system (CNS) metastases
• •History of hypersensitivity to LDE225 or to drugs of similar chemical classes
• •Patients who have neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or are on concomitant treatment with drugs that are recognized to cause rhabdomyolysis, such as 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) inhibitors (statins), clofibrate and gemfibrozil, and that cannot be discontinued at least 2 weeks prior to starting LDE225 treatment. If it is essential that the patient stays on a statin to control hyperlipidemia, only pravastatin may be used with extra caution
• •Patients who are planning on embarking on a new strenuous exercise regimen after initiation of study treatment: Muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided while on LDE225 treatment
• •Patients who have taken part in an experimental drug study within 4 weeks or 5 half-lives, whichever is longer, of initiating treatment with LDE225
• •Patients who are receiving other anti-neoplastic therapy besides Docetaxel (e.g. chemotherapy, targeted therapy or radiotherapy) concurrently or within 2 weeks of starting treatment with LDE225
• •Patients who are receiving treatment with medications known to be moderate and strong inhibitors or inducers of Cytochrome P450 3A4/5 (CYP3A4/5) or drugs metabolized by Cytochrome P450 2B6 (CYP2B6) or Cytochrome P450 2C9 (CYP2C9) that have narrow therapeutic index, and that cannot be discontinued before starting treatment with LDE225. Medications that are strong CYP3A4/5 inhibitors should be discontinued at least 7 days and strong CYP3A/5 inducers for at least 2 weeks prior to starting treatment with LDE225
• •Patients who require the use of warfarin (substrate of CYP2C9) cannot be enrolled as LDE225 is a competitive inhibitor of CYP2C9 based on in-vitro data
• •Impaired cardiac function or clinically significant heart disease, including any one of the following: Angina pectoris within 3 months Acute myocardial infarction within 3 months QTcF \> 450 msec for males and \> 470 msec for females on the screening ECG A past medical history of clinically significant ECG abnormalities or a family history of prolonged QT-interval syndrome Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
• •Prior to study entry any ECG abnormality has to be documented by the investigator as not medically relevant