A Study of VEGF Tyrosine Kinase Inhibitor (Pazopanib) in Men With High-Risk Prostate Cancer Followed by Radical Prostatectomy and Pelvic Lymph Node Dissection

Inclusion Criteria:

* Men ≥ 18 years of age
* Histological documentation of adenocarcinoma of the prostate, with available biopsy pathology. Biopsy material must be available for pathologic review.
* All patients must meet one or more of the following disease features: clinical stage greater than or equal to T3; Primary Gleason score of 4 OR Gleason score of 8, 9 or 10; serum prostate-specific antigen (PSA) ≥ 20 ng/mL; Prostate MRI findings consistent with T3 disease; Any clinical stage and PSA (prostate-specific antigen) \>10 and Gleason score 7; A Kattan nomogram predicted probability of being free from biochemical progression at 5 years after surgery of \< 60%.
* Patients must have a PSA (prostate-specific antigen) ≥ 2 ng/mL at the time of diagnosis of prostate cancer or later.
* No prior radiation or chemotherapy for prostate cancer treatment.
* Scheduled for radical prostatectomy surgery.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
* Patients may have been treated with up to 4 months of androgen deprivation therapy.
* No clinical evidence of metastatic prostate cancer, or enlarged pelvic lymph nodes in the imaging studies.
* Resected lymph nodes must be provided for all subjects for biomarker analysis immediately (same day) after surgery (radical prostatectomy).
* Adequate organ system function as defined by study Protocol

  1. Subjects may not have had a transfusion within 7 days of screening assessment.
  2. Concomitant elevations in bilirubin and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) above 1.0 x upper limit of normal (ULN) are not permitted.
  3. If urine protein count (UPC) =\>1, then a 24-hour urine protein must be assessed. Subjects must have a 24-hour urine protein value \<1 to be eligible.
* Subjects must provide written informed consent within one month prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow up.

Exclusion Criteria:

* Clinical evidence of metastatic prostate cancer.
* Prior malignancy. No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years.
* Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to: Active peptic ulcer disease Known intraluminal metastatic lesion/s with risk of bleeding Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment.
* Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:

  * Malabsorption syndrome or
  * Major resection of the stomach or small bowel.
* Corrected QT interval (QTc) \> 480 msecs Note: Correction method should be reported
* History of any one or more of the following cardiovascular conditions within the past 6 months:

  * Cardiac angioplasty or stenting
  * Myocardial infarction
  * Unstable angina
  * Coronary artery bypass graft surgery
  * Symptomatic peripheral vascular disease
  * Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
* No evidence of preexisting uncontrolled hypertension. If the patient has a history of elevated blood pressure at baseline then they must have controlled hypertension documented and confirmed by 2 consecutive blood pressure readings taken within 1 hour. The baseline systolic blood pressure readings must be =\<140 mm Hg, and the baseline diastolic blood pressure readings must be =\<90 mm Hg.

Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Following antihypertensive medication initiation or adjustment, blood pressure (BP) must be re-assessed three times at approximately 2-minute intervals. At least 24 hours must have elapsed between anti-hypertensive medication initiation or adjustment and Blood Pressure measurement. These three values should be averaged to obtain the mean diastolic blood pressure (DBP) and the mean systolic blood pressure (SBP). The mean SBP / DBP ratio must be \<140/90 mm Hg (OR 150/90 mm Hg, if this criterion is approved by the Huntsman Cancer Institute (HCI) Data Safety and Monitoring Committee (DSMC) Chair or Co-chair) in order for a subject to be eligible for the study (see protocol for details on Blood Pressure control and re-assessment prior to study enrollment).

* History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
* Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major surgery).
* Evidence of active bleeding or bleeding diathesis.
* Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage Note: Lesions infiltrating major pulmonary vessels (contiguous tumour and vessels) are excluded; however, the presence of a tumor that is touching, but not infiltrating (abutting) the vessels is acceptable (CT (computed tomography) with contrast is strongly recommended to evaluate such lesions).

  * Large protruding endobronchial lesions in the main or lobar bronchi are excluded; however, endobronchial lesions in the segmented bronchi are allowed.
  * Lesions extensively infiltrating the main or lobar bronchi are excluded; however, minor infiltrations in the wall of the bronchi are allowed.
* Recent hemoptysis (=\> ½ teaspoon of red blood within 8 weeks before first dose of study drug).
* Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
* Unable or unwilling to discontinue use of prohibited medications listed in the protocol for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study.
* Treatment with any of the following anti-cancer therapies:

  * radiation therapy, chemotherapy, immunotherapy, biologic therapy, investigational therapy
  * surgery or tumor embolization within 14 days prior to the first dose of pazopanib OR hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of Pazopanib
* Administration of any non-oncologic investigational drug within 30 days or 5 half lives whichever is longer prior to receiving the first
* Any ongoing toxicity from prior hormonal therapy that is \>Grade 1 and/or that is progressing in severity.