Study of TRC105 With Abiraterone and With Enzalutamide in Prostate Cancer Patients Progressing on Therapy
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: TRC105; Abiraterone; Enzalutamide
Intervention description: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks; Patients who are progressing on Abiraterone will undergo a washout period and then continue treatment with standard dosing of Abiraterone plus TRC105.; Patients who are progressing on Enzalutamide will undergo a washout period and then continue standard treatment with Enzalutamide plus TRC105.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Bayesian design
Masking: None (Open Label)
Enrollment: 11.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Prostate Cancer; Metastatic Prostate Cancer; Castration Resistant Prostate Cancer; Metastatic Castration Resistant

Summary:

      This research study is being done to measure the clinical benefit of TRC105 in combination
      with abiraterone or enzalutamide in metastatic, castration-resistant prostate cancer patients
      who are taking either abiraterone or enzalutamide and showing signs of biochemical
      progression without radiographic progression. A patient who is progressing on AR-therapy will
      continue the same AR-therapy on study with the addition of TRC105. The two arms will accrue
      in parallel and independently.
    

Eligibility criteria:

        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.