A Phase I/II Study of TRC105 in Metastatic Castrate Resistant Prostate Cancer (CRPC)

Inclusion Criteria

-INCLUSION CRITERIA:

1. Patients must have histopathological confirmation of prostate cancer by the
Laboratory of Pathology of the NCI, Pathology Department of the National Naval
Medical Center or Pathology Department of Walter Reed Army Medical Center prior to
entering this study. Patients whose pathology specimens are no longer available may
be enrolled in the trial if the patient has a clinical course consistent with
prostate cancer and available documentation from an outside pathology laboratory of
the diagnosis. In cases where original tissue blocks or archival biopsy material is
available, efforts will be made to contact referring physicians and outside pathology
departments to have the material forwarded to the research team for use in
correlative studies.

2. Patients must have metastatic progressive castrate-resistant prostate cancer defined
as progressive disease (see below) despite surgical castration or ongoing use of
gonadotropin-releasing hormone agonists with confirmed castrate levels of
testosterone.

Criteria of progression for trial eligibility are defined from the Prostate Cancer
Clinical Trials Working Group-2. Clinically progressive prostate cancer must be
evidenced and documented by any of the following parameters:

1. Two consecutively rising PSA values at a minimum of 1-week intervals (2.0 ng/mL
is the minimum starting value for PSA)

2. Appearance of one or more new lesion on bone scans

3. Progressive measurable disease by RECIST 1.1

Patients on flutamide for at least 6 months must have disease progression at least 4
weeks after withdrawal. Patients on bicalutamide or nilutamide for at least 6 months
must have progression at least 6 weeks after withdrawal.

All patients enrolled will be required to have measurable or non-measurable disease
on imaging studies.

3. Phase II study patients enrolled onto Arm 1 (chemotherapy-na ve) may not have
received any prior chemotherapy or antiangiogenic therapy for metastatic prostate
cancer. Those patients enrolled onto Arm 2 must have evidence of disease progression
(per criteria stated above) despite prior docetaxel. Any number of prior treatment
lines is acceptable.

4. Age greater than or equal to 18 years.

5. Life expectancy of greater than 3 months.

6. ECOG performance status 0-2.

7. Patients must have normal organ and marrow function as defined below:

- Absolute neutrophil count greater than or equal to 1,500/mcL

- Platelets greater than or equal to 100,000/mcL

- Total bilirubin less than or equal to 1.5 times upper normal limits or less than
3 mg/dl in subjects with Gilbert's Syndrome

- AST/ALT less than or equal to 2.5 times upper limit of normal

- Creatinine less than or equal to 1.5 times upper normal limits OR creatinine
clearance greater than or equal to 40 mL/min/1.73 m(2) for patients with
creatinine levels above institutional normal, as calculated by the Cockcroft
Gault formula.

8. Patients must have recovered from any acute toxicity related to prior therapy,
including surgery. Toxicity should be less than or equal to grade 1 or returned to
baseline.

9. All patients who have not undergone bilateral surgical castration must continue
suppression of testosterone production by appropriate usage of GnRH agonists or
antagonists.

10. Patients must not have other invasive malignancies (within the past 2 years with the
exception of non-melanoma skin cancers or non-invasive bladder cancer).

11. Enrolled patients must agree to use adequate contraception (hormonal or barrier
method of birth control; abstinence) prior to study entry, the duration of study
participation and 3 months after the end of the treatment.

12. Patient must be able to understand and willing to sign a written informed consent
document.

13. Patients on a stable dose of steroids of 10 mg/day or less can continue on steroids
if they are on peptic ulcer disease prophylaxis with an H2-blocker or proton pump
inhibitor.

EXCLUSION CRITERIA:

1. Patients who have had chemotherapy, large field radiotherapy, or major surgery must
wait 3 weeks prior to entering the study.

2. Patients may not be receiving any agents not approved by the FDA within the past 4
weeks.

3. Patients with known brain metastases will be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse
events.

4. Proteinuria, as demonstrated by a 24 hour protein of >= 2000 mg. Urine protein will
be screened by urine protein-creatinine ratio (UPC). For UPC ratio > 1.0, a 24-hour
urine protein will need to be obtained and the level should be < 2000 mg for patient
enrollment.

5. Uncontrolled intercurrent illness including, but not limited to, hypertension
(systolic BP > 160, diastolic BP > 100), ongoing or active systemic infection,
symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or
psychiatric illness/social situations that would limit compliance with study
requirements.

6. Thrombolytic or treatment-dose anticoagulant use within 10 days prior to first dose
with TRC105.

7. Hemorrhage within 30 days of dosing.

8. History of peptic ulcer disease or gastritis within 6 months of TRC105
administration, unless patient has received adequate treatment for peptic ulcer
disease and has evidence of complete resolution documented by EGD.

9. QTc > 500 msec.

10. Known HIV-positive patients are excluded.

11. History of hypersensitivity reaction to human or mouse antibody products.

12. Patients with a history of familial bleeding disorders.

13. Patients with a history of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu
syndrome).

14. Use of non-steroidal anti-inflammatory drugs (NSAIDs) beginning 14 days prior to the
first TRC105 dose, with the exception of aspirin when clinically indicated.