Study of TRC105 With Abiraterone and With Enzalutamide in Prostate Cancer Patients Progressing on Therapy

Exclusion Criteria

• •1. Non-PSA producing prostate cancers- such as small cell prostate cancers or those prostate cancers which exhibit radiographic progression without PSA rise
• •2. Inability to tolerate standard doses of abiraterone (1000 mg daily) or enzalutamide (160 mg daily).
• •3. Other prior malignancy requiring active anticancer therapy
• •4. Prior exposure to TRC105 or any CD105 targeted antibody
• •5. Any major surgical procedure within 2 weeks of starting therapy
• •6. Uncontrolled chronic hypertension defined as sustained by systolic pressure (SBP) \>150 mmHg or diastolic pressure (DBP) \>90 despite optimal therapy.
• •7. Active bleeding or pathologic conditions that carries a high bleeding risk
• •8. Use of thrombolytics within 10 days prior to the first day of TRC105
• •9. Known hypersensitivity to Chinese hamster ovary products or other recombinant human, chimeric, or humanized antibodies
• •10. A known diagnosis of Osler-Weber-Rendu syndrome
• •11. Ascites or pericardial or pleural effusion requiring external drainage procedures
• •12. History of untreated brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease. Patients with radiated or resected lesions are permitted, provided the lesions are fully treated and inactive, patients are asymptomatic, and no steroids have been administered for at least 28 days. Imaging for CNS disease will not be required for screening unless there is a history of a neurological finding such as new onset weakness or numbness that cannot be explained by other medical history.
• •13. Acute cardiovascular event within the past 6 months. An acute cardiovascular event will be defined as a myocardial infraction, NYHA Class II or worse congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA), or CABG. Deep venous thrombosis within 6 months, unless the patient is anti-coagulated without the use of warfarin for at least 2 weeks. In this situation, low molecular weight heparin is preferred.