Inclusion Criteria:

1. Histologically or cytologically confirmed adenocarcinoma of the prostate without
small cell features;

2. At least 18 years of age when signing the Informed Consent;

3. Presence of metastatic disease on bone scan or CT/MRI imaging;

4. Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH)
analogue or orchiectomy (i.e., medical or surgical castration);

5. For patients who have not had an orchiectomy, there must be a plan to maintain
effective GnRH-analogue therapy for the duration of the trial;

6. Serum testosterone level < 50 ng/dL at the Screening Visit;

7. Progressive disease on or following docetaxel-based chemotherapy with medical or
surgical castration. Patients who are intolerant of docetaxel are also allowed.
Disease progression for study entry is defined as one or more of the following three
criteria: 1) PSA progression defined by a minimum of three rising PSA levels with an
interval of ≥ 1 week between each determination. The PSA value at the Screening visit
should be ≥ 2 μg/L (2 ng/mL); 2) Soft tissue disease progression defined by RECIST
1.1; 3) Bone metastatic disease progression defined by one or more new lesions on
bone scan that are not clinically consistent with tumor flare;

8. No more than three prior chemotherapy regimens with at least one regimen containing
docetaxel (unless intolerant as per # 7 above);

9. Karnofsky Performance Status of >70;

10. Estimated life expectancy of at least three months;

11. Able to swallow the study drug and comply with study requirements;

12. Willing and able to give informed consent.

Exclusion Criteria:

1. Subjects > 80 years old (dose escalation phase only, due to lower clearance in
elderly patients);

2. Severe concurrent disease, infection, or co-morbidity that, in the judgment of the
investigator, would make the patient inappropriate for enrollment;

3. Metastases in the brain or active epidural disease (NOTE: patients with treated
epidural disease are allowed provided follow up imaging documents stability of
epidural disease);

4. Absolute neutrophil count < 1,200/μL, platelet count < 100,000/μL, and hemoglobin <9
g/dL at the Screening Visit; (NOTE: patients may not have received any growth factors
or blood transfusions within seven days of the hematologic laboratory values obtained
at the Screening Visit)

5. Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST)
>1.5 times the upper limit of normal at the Screening Visit;

6. Creatinine > 1.5 x ULN at the Screening visit;

7. History of another malignancy within the previous 3 years other than non-melanomatous
skin cancer or non-invasive bladder cancer treated with curative intent;

8. Treatment with androgen receptor antagonists (bicalutamide, flutamide, nilutamide,
MDV3100), 5-α reductase inhibitors (finasteride, dutasteride), estrogens (ie DES),
sipuleucel-T, or chemotherapy within 28 days of Day 1 visit or plans to initiate
treatment with any of these treatments during the study;

9. Use of herbal products that may decrease PSA levels or systemic corticosteroids
greater than the equivalent of 10 mg of prednisone/prednisolone per day within four
weeks of Day 1 visit;

10. Ongoing treatment with warfarin unless the international normalized ratio (INR) is
well controlled and below 4

11. Exposure to ketoconazole or other strong CYP3A4 inhibitors or inducers intravenously
or orally within 28 days prior to Day 1 Visit. For abiraterone acetate or TAK700, 14
days washout is needed.

12. Ongoing treatment with sensitive CYP1A2 substrates or CYP1A2 substrates with narrow
therapeutic range (Appendix 3).

13. Ongoing treatment with CYP3A4 substrates with narrow therapeutic range (Appendix 3).

14. Radiation therapy within 2 weeks (if single fraction of radiotherapy within 2 weeks)
and radionuclide therapy within 8 weeks of Day 1 visit;

15. Planned palliative procedures for alleviation of bone pain such as radiation therapy
or surgery;

16. Structurally unstable bone lesions suggesting impending fracture;

17. Clinically significant cardiovascular disease including:myocardial infarction within
6 months, uncontrolled angina within 3 months, congestive heart failure, Diagnosed or
suspected congenital long QT syndrome; significant ventricular arrhythmias, Prolonged
corrected QT interval by the Fridericia or Bazett correction formula, History of
Mobitz II second degree or third degree heart block without a permanent pacemaker in
place; Hypotension (systolic blood pressure < 86 mMHg or bradycardia with a heart
rate < 50 beats per minute on any ECG taken at the Screening or Day 1 visit;
Uncontrolled hypertension; TIA or stroke/CVA within 6 months of Day 1 visit; Rest
limb claudication or ischemia within 6 months of Day 1 visit

18. Use of an investigational agent within four weeks of Day 1 visit or plans to initiate
treatment with an investigational agent during the study;

19. Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic
ulcer disease within last three months);

20. Major surgery within four weeks prior to Day 1 visit.

21. Presence of NCI CTC grade >1 peripheral neuropathy

22. History of pancreatitis

23. Known positive serology for HIV (patients with known history of HIV will be excluded
because of potential for unforeseen toxicity and morbidity in an immunocompromised
host).

24. Chronic hepatitis B or C with advanced, decompensated hepatic disease, or cirrhosis
of the liver or history of a chronic viral hepatitis or known viral hepatitis carrier
(patients recovered from hepatitis will be allowed to enter the study).

25. Documented prior disease progression on tasquinimod -