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

Inclusion Criteria:

1. History of metastatic, castration-resistant prostate cancer with rising PSA on either abiraterone or enzalutamide

   * PSA rise will be defined as an increase in PSA of 0.2 ng/mL or higher on at least 2 separate occasions greater than 1 week apart while on either abiraterone or enzalutamide
   * If there is a drop in serum PSA after the first rise, and the patient has another PSA rise which is greater than the first, the patient will still be considered eligible.
2. ECOG 0-2
3. Resolution of adverse events results as described below.

   * Laboratory abnormalities must meet values specified below in criteria #4
   * If the patient's most recent line of therapy is treatment with abiraterone or enzalutamide, then all adverse events must be resolved to Grade 2 or better
   * If the most recent line of therapy is any other treatment for mCRPC then all Adverse events must be resolved to grade 1 or better, with the exception of fatigue, alopecia and neuropathy (which must resolve to CTCAE grade 2)
4. Adequate organ function defined by:

   * AST and ALT \< 2.5 x ULN
   * Total serum bilirubin \< 1.5 x ULN
   * Platelets \> 60,000
   * Hgb \> 8.5 g/dL
   * Serum Cr \<1.5 x ULN or a creatinine clearance \> 30.
   * INR ≤ 1.2 unless the patient is receiving a direct Factor Xa inhibitor or a direct thrombin inhibitor
5. Patients must be surgically sterile or must agree to use effective contraception during the study and for 3 months following last dose of TRC105. The definition of effective contraception will be based on the judgment of the Principal Investigator or a designated associate. Abstinence from intercourse is an acceptable form of contraception.

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.