Pazopanib as Second Line Therapy in Patients With Metastatic Prostate Cancer Refractory to Total Androgen Blockade

Exclusion Criteria

• •Subjects meeting any of the following criteria must not be enrolled in the study:
• •1. History of another malignancy.
• •Note: Subjects who have had another malignancy and have been disease-free for 3 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
• •2. History or clinical evidence of central nervous system (CNS) metastases.
• •Note: Subjects who have previously-treated CNS metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and meet all 3 of the following criteria are eligible:
• •* Are asymptomatic and,
• •* Have had no evidence of active CNS metastases for ≥ 6 months prior to enrollment and,
• •* Have no requirement for steroids or enzyme-inducing anticonvulsants (EIAC).
• •3. Clinically significant gastrointestinal abnormalities including, but not limited to:
• •* Malabsorption syndrome,
• •* Major resection of the stomach or small bowel that could affect the absorption of study drug,
• •* Active peptic ulcer disease,
• •* Inflammatory bowel disease,
• •* Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation,
• •* History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.
• •4. Presence of uncontrolled infection.
• •5. Prolongation of corrected QT interval (QTc) \> 480 milliseconds (msecs).
• •6. History of any one or more of the following cardiovascular conditions within the past 12 months:
• •* Cardiac angioplasty or stenting,
• •* Myocardial infarction,
• •* Unstable angina,
• •* Symptomatic peripheral vascular disease,
• •* Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA).
• •7. History of cerebrovascular accident (CVA) including transient ischemic attack (TIA).
• •8. History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anticoagulating agents for at least 6 weeks are eligible.
• •9. Poorly controlled hypertension \[defined as systolic blood pressure (SBP) of ≥150mmHg or diastolic blood pressure (DBP) of ≥ 90 mmHg\].
• •Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Blood pressure must be re-assessed on two occasions that are separated by a minimum of 24 hours. The mean SBP/DBP values from each blood pressure assessment must be \< 150/90mmHg in order for a subject to be eligible for the study. See Section 6.3.2 for instruction on blood pressure measurement and obtaining mean blood pressure values.
• •10. Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer.
• •11. Evidence of active bleeding or bleeding diathesis
• •12. Hemoptysis within 6 weeks of first dose of study drug.
• •13. Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study.
• •14. Prohibited medications within 28 days unless the half-life of the medication is longer than 28 days, will not be permitted.
• •15. Use of an investigational agent, including an investigational anti-cancer agent, within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study drug.
• •16. Prior use of an investigational or licensed drug that targets VEGF or VEGF receptors (e.g., bevacizumab, sunitinib, sorafenib, etc), or are mTOR inhibitors (eg. temsirolimus, everolimus, etc).
• •17. Is now undergoing and/or has undergone in the last 4 weeks immediately prior to first dose of study drug, (surgery, tumor embolization, chemotherapy, radiation therapy, immunotherapy, or biological therapy)
• •18. Any ongoing toxicity from prior anti-cancer therapy that is \> Grade 1 and/or that is progressing in severity.
• •19. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib.