Inclusion Criteria:
1. Male, age ≥ 18 years old.
2. ECOG performance status of 0 or 1
3. Histologic evidence of adenocarcinoma of the prostate who are deemed candidates for
curative radical prostatectomy.
4. Planned robotic or laparoscopic prostatectomy technique.
5. Low risk for conversion to open prostatectomy, in the opinion of the treating surgeon.
6. Intermediate-high or high risk, clinically localized disease by the following
criteria:
- Prostate cancer in at least 2 cores with a Gleason score ≥ 7 (4+3 or 3+4) in at
least 1 of those cores.
- No definite evidence of metastasis, in the opinion of the investigator.
7. Adequate organ function as defined by the following criteria within 14 days prior to
first dose of study treatment:
- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤3 x local laboratory
upper limit of normal (ULN)
- Total serum bilirubin ≤1.5 x ULN, (for subjects with Gilbert's disease ≤ 3 x ULN)
- Absolute neutrophil count (ANC) ≥1500/L without granulocyte colony-stimulating
factor support.
- White blood cell count ≥ 2500/mm3
- Serum albumin ≥ 2.8 g/dl
- Platelets ≥100,000/mm3
- Hemoglobin ≥9.0 g/dL
- Serum calcium ≤12.0 mg/dL
- Serum creatinine ≤ 2.0 x ULN or calculated creatinine clearance ≥ 30mL/min.
- Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol).
8. Written Authorization for Use and Release of Health and Research Study Information
(HIPAA authorization per institutional requirements)
9. Evidence of a personally signed and dated informed consent document indicating that
the subject has been informed of all pertinent aspects of the trial.
10. Willing/able to adhere to the prohibitions and restrictions specified in this
protocol.
11. Agrees to use a condom (even men with vasectomies) and another effective method of
birth control if subject is having sex with a woman who is pregnant or a woman of
childbearing potential while on study drug and for 4 months following the last dose of
study drug.
Exclusion Criteria:
1. Prior treatment for prostate cancer.
2. Major surgery or radiation therapy within 4 weeks of Day 1 on study.
3. Planned radiation therapy until at least 4 weeks after prostatectomy.
4. NCI CTCAE v4.0 grade 3 hemorrhage within 4 weeks of Day 1 on study.
5. Prothrombin time (PT)/INR or partial thromboplastin time (PTT) test ≥ 1.3 x the
laboratory ULN within 14 days before Day 1 on study (Arm A subjects only) or within 14
days of the completion of screening (Arm B subjects only).
6. Concomitant anticoagulation with oral anticoagulants (e.g., warfarin, direct thrombin
and Factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel). However, low-dose
aspirin for cardio protection is allowed (per local applicable guidelines).
7. History of or known metastatic prostate cancer.
8. QTcf interval > 500 msec on baseline EKG.
9. The subject has uncontrolled, significant intercurrent or recent illness including,
but not limited to, the following conditions:
a. Cardiovascular disorders:
i. Symptomatic congestive heart failure (CHF) New York Heart Association Class 3 or 4,
unstable angina pectoris, ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2.
coronary/peripheral artery bypass graft (CABG), within 6 months prior to screening.
ii. Stroke (including transient ischemic attack [TIA]), cerebrovascular accident
(CVA), myocardial infarction (MI), or other ischemic event, or thromboembolic event
(eg, deep venous thrombosis, pulmonary embolism (PE)) within 6 months prior to
screening.
b. Gastrointestinal (GI) disorders including those associated with a high risk of
perforation or fistula formation:
i. Evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory
bowel disease (eg, Crohn's disease), diverticulitis, cholecystitis, symptomatic
cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic
duct or common bile duct, or gastric outlet obstruction.
ii. Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess
within 6 months before first dose.
Note: Complete healing of an intra-abdominal abscess must be confirmed before first
dose.
c. Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5
ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage)
within 12 weeks before first dose.
d. Serious non-healing wound/ulcer/bone fracture. e. Other clinically significant
disorders that would preclude safe study participation.
10. Hypertension that cannot be controlled by medications (>140/90 mm Hg despite optimal
medical therapy).
11. Pre-existing thyroid abnormality with thyroid function that cannot be maintained in
the normal range with medication.
12. Concurrent treatment on another clinical trial. Supportive care trials or
non-treatment trials, e.g. QOL, are allowed.
13. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or study
drug administration, or may interfere with the interpretation of study results, and in
the judgment of the investigator would make the subject inappropriate for entry into
this study.
14. Inability to swallow tablets.
15. Diagnosis of another malignancy within 2 years before first dose of study treatment,
except for superficial skin cancers, or localized, low grade tumors deemed cured and
not treated with systemic therapy.
