Inclusion Criteria:

- Adenocarcinoma of the prostate that is metastatic or unresectable and for which
standard curative options do not exist

- Radiographic evidence of metastatic prostate cancer

- Progressive disease despite ongoing androgen deprivation therapy (ADT), defined as
castration resistant prostate cancer (CRPC)

- Other than ongoing prior treatment with other hormonal agents such as antiandrogens
or ketoconazole must have been stopped at least two weeks prior to enrollment

- Have received prior docetaxel-based chemotherapy for prostate cancer within the past
12 months. Such chemotherapy must have been stopped at least 3 weeks prior to the
first dosing in this study

- Life expectancy of at least 12 weeks

- Must agree to use adequate contraception prior to study entry and for the duration of
study participation

Exclusion Criteria:

- Prior treatment with enzalutamide, TOK-001, or ARN-509

- Participants who have received more than two prior chemotherapy regimens for
metastatic CRPC

- Receiving any other investigational anticancer agents

- Known brain metastases

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to tivozanib or enzalutamide

- Radiotherapy or minor surgical procedure within 2 weeks, or major surgical procedure
within 4 weeks prior to administration of first dose of study drug; inadequate
recovery from prior surgical procedure

- History of seizure of condition that may predispose to seizure

- Significant cardiovascular disease

- Non-healing wound, bone fracture or skin ulcer

- Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis or other
gastrointestinal condition with increased risk of perforation; history of abdominal
fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks
prior to administration of first dose of study drug

- Serious/active infection or infection requiring parenteral antibiotics

- Significant thromboembolic or vascular disorders within 6 months prior to
administration of first dose of study drug

- Currently active second primary malignancy, including hematologic malignancies,
except for non-melanoma skin cancers, in situ cervical cancer, and ductal or lobular
carcinoma in situ of the breast

- History of genetic or acquired immune suppression disease such as HIV; subjects on
immune suppressive therapy for organ transplant

- Inability to swallow capsules, malabsorption syndrome or gastrointestinal disease
that severly affects the absorption of study drugs, major resection of the stomach or
small bowel, or gastric bypass procedure

- Significant bleeding disorders within 6 months prior to administration of first dose
of study drug

- Psychiatric disorder or altered mental status precluding informed consent or
protocol-related testing