A Neoadjuvant, Randomized, Phase II Study of VEGF Tyrosine Kinase Inhibitor (Pazopanib) in Men With High-Risk Prostate Cancer Followed by Radical Prostatectomy and Pelvic Lymph Node Dissection
- Men ≥ 18 years of age
- Histological documentation of adenocarcinoma of the prostate, with available biopsy
pathology. Biopsy material must be available for central pathologic review.
- All patients must meet one or more of the following features: clinical stage T3
disease; Gleason score of 8, 9 or 10; serum PSA(prostate-specific antigen) ≥ 20
ng/mL; Gleason score of 7 and prostate MRI findings consistent with T3 disease;
Clinical stage T2a, T2b, T2c 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.
- 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.
- Fresh tumor tissue and 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. Subjects receiving anticoagulant therapy are eligible if their INR
(international normalized ratio) is stable and within the recommended range for
the desired level of anticoagulation.
3. Concomitant elevations in bilirubin and AST/ALT (aspartate
aminotransferase/alanine aminotransferase) above 1.0 x ULN (upper limit of
normal) are not permitted.
- If UPC (urine protein count) =>1, then a 24-hour urine protein must be assessed.
Subjects must have a 24-hour urine protein value <1 to be eligible. Use of urine
dipstick for renal function assessment is not acceptable.
- 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.
- Prior radiation or chemotherapy for prostate cancer treatment.
- 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, Chrohn'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
- 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) (To be added as an Appendix in the protocol, See Section YYY
Appendix Y for description)
- No evidence of preexisting uncontrolled hypertension as documented 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 and the mean systolic blood pressure. The mean
SBP / DBP ratio must be <140/90 mmHg (OR 150/90 mm Hg, if this criterion is approved by
Safety Review Team) 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
- 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
- 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
- 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, surgery or tumor embolization within 14 days prior to the
first dose of pazopanib OR
- chemotherapy, immunotherapy, biologic therapy, investigational therapy 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 anti-cancer therapy that is >Grade 1 and/or that is
progressing in severity, except alopecia.