A Study of VEGF Tyrosine Kinase Inhibitor (Pazopanib) in Men With High-Risk Prostate Cancer Followed by Radical Prostatectomy and Pelvic Lymph Node Dissection
A Study of VEGF Tyrosine Kinase Inhibitor (Pazopanib) in Men With High-Risk Prostate Cancer Followed by Radical Prostatectomy and Pelvic Lymph Node Dissection
The area around a tumor ("pre-metastatic niche") may be an area to which cancer cells are
 attracted. The study doctor will take blood and tumor samples to look for certain features
 linked with response to treatment so that they can predict which future patients may benefit
 from this therapy. The purpose of this study is to see if the drug pazopanib can be used to
 reduce the amount of pre-metastatic niche in the patient's lymph nodes (a common site for
 prostate cancer to spread). Down the line, this may help to prevent prostate cancer from
 coming back after surgery.
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.