A Study of Pazopanib as Second Line Therapy in Patients With Metastatic Prostate Cancer Who Have Received Prior Therapy With an LHRH Agonist.
1. Diagnosis of adenocarcinoma of the prostate histology, currently on total androgen
blockage with a bicalutamide.
2. Subjects must provide written informed consent prior to administration of pazopanib
or the performance of any study-specific procedures or assessments, and must be
willing to comply with treatment and follow up. Procedures conducted as part of the
subject's routine clinical management (e.g., blood count, imaging study) and obtained
prior to signing of informed consent may be utilized for screening or baseline
purposes provided these procedures are conducted as specified in the protocol. Note:
It is not necessary that informed consent be obtained within the protocol-specified
3. Received no prior second line hormone therapy or any chemotherapy. No prior
bevacizumab, mTOR inhibitor, sunitinib, sorafenib or other VEGF TKI) for advanced or
metastatic prostate cancer.
4. Must have metastatic diagnosis, meaning disease beyond the prostate gland.
5. A progressing PSA of ≥ 3, the PSA will be measured in ≥ 14 days.
6. KPS of ≥ 70
7. Age ≥ 18 years old
8. Adequate organ system functions:
- Absolute neutrophil count (ANC) ≥ 1.5 X 109/L
- Hemoglobin ≥ 9 g/dL
- Platelets ≥ 100 X 109/L
- International normalized ratio (INR) ≤ 1.2 X upper limit of normal (ULN)
- Partial thromboplastin time (PTT) ≤ 1.2 X ULN
- Total bilirubin ≤ 1.5 X ULN
- AST and ALT ≤ 2.5 X ULN
- Calculated creatinine clearance ≥ 30 mL/min
- Urine Protein to Creatinine Ratio (UPC)2 < 1
- Total serum calcium concentration < 12.0mg/dL
- Subjects may not have had a transfusion within 7 days of screening
- If UPC ≥ 1, then a 24-hour urine protein must be assessed. Subjects must
have a 24-hour urine protein value < 1 g to be eligible.
9. Left ventricular ejection fraction (LVEF) ≥ 55% as assessed by echocardiography or
multigated acquisition (MUGA) scan. The same modality used at baseline must be
applied for subsequent evaluations.
Subjects meeting any of the following criteria must not be enrolled in the study:
1. History of another malignancy.
Note: Subjects who have had another malignancy and have been disease-free for 3
years, or subjects with a history of completely resected non-melanomatous skin
carcinoma or successfully treated in situ carcinoma are eligible.
2. History or clinical evidence of central nervous system (CNS) metastases.
Note: Subjects who have previously-treated CNS metastases (surgery ± radiotherapy,
radiosurgery, or gamma knife) and meet all 3 of the following criteria are eligible:
- Are asymptomatic and,
- Have had no evidence of active CNS metastases for ≥ 6 months prior to enrollment
- Have no requirement for steroids or enzyme-inducing anticonvulsants (EIAC).
3. Clinically significant gastrointestinal abnormalities including, but not limited to:
- Malabsorption syndrome,
- Major resection of the stomach or small bowel that could affect the absorption
of study drug,
- Active peptic ulcer disease,
- Inflammatory bowel disease,
- Ulcerative colitis, or other gastrointestinal conditions with increased risk of
- History of abdominal fistula, gastrointestinal perforation, or intra abdominal
abscess within 28 days prior to beginning study treatment.
4. Presence of uncontrolled infection.
5. Prolongation of corrected QT interval (QTc) > 480 milliseconds (msecs).
6. History of any one or more of the following cardiovascular conditions within the past
- Cardiac angioplasty or stenting,
- Myocardial infarction,
- Unstable angina,
- Symptomatic peripheral vascular disease,
- Class III or IV congestive heart failure, as defined by the New York Heart
7. History of cerebrovascular accident (CVA) including transient ischemic attack (TIA).
8. History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the
past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic
anticoagulating agents for at least 6 weeks are eligible.
9. Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥150mmHg
or diastolic blood pressure (DBP) of ≥ 90 mmHg].
Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior
to study entry. Blood pressure must be re-assessed on two occasions that are
separated by a minimum of 24 hours. The mean SBP/DBP values from each blood pressure
assessment must be < 150/90mmHg in order for a subject to be eligible for the study.
See Section 6.3.2 for instruction on blood pressure measurement and obtaining mean
blood pressure values.
10. Prior major surgery or trauma within 28 days prior to first dose of study drug and/or
presence of any non-healing wound, fracture, or ulcer.
11. Evidence of active bleeding or bleeding diathesis
12. Hemoptysis within 6 weeks of first dose of study drug.
13. Any serious and/or unstable pre-existing medical, psychiatric, or other conditions
that could interfere with subject's safety, obtaining informed consent or compliance
to the study.
14. Prohibited medications within 28 days unless the half-life of the medication is
longer than 28 days, will not be permitted.
15. Use of an investigational agent, including an investigational anti-cancer agent,
within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study
16. Prior use of an investigational or licensed drug that targets VEGF or VEGF receptors
(e.g., bevacizumab, sunitinib, sorafenib, etc), or are mTOR inhibitors (eg.
temsirolimus, everolimus, etc).
17. Is now undergoing and/or has undergone in the last 4 weeks immediately prior to first
dose of study drug, (surgery, tumor embolization, chemotherapy, radiation therapy,
immunotherapy, or biological therapy)
18. Any ongoing toxicity from prior anti-cancer therapy that is > Grade 1 and/or that is
progressing in severity.
19. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to pazopanib.