A Study of Pazopanib as Second Line Therapy in Patients With Metastatic Prostate Cancer Who Have Received Prior Therapy With an LHRH Agonist.
Overview
- Phase
- Phase 2
- Intervention
- Pazopanib (GW786034)
- Conditions
- Prostate Cancer
- Sponsor
- Illinois CancerCare, P.C.
- Enrollment
- 11
- Locations
- 2
- Primary Endpoint
- Response Rate at 12 Weeks
- Status
- Terminated
- Last Updated
- 12 years ago
Overview
Brief Summary
A growing body of literature supports the role of angiogenesis in the development and spread of a variety of human cancers including prostate cancer.
- Vascular endothelial growth factor (VEGF) expression is low in normal prostate tissue, but markedly increased in tumor tissues, and has a positive association with tumor stage and grade
- Plasma VEGF levels are significantly elevated in patients with hormone refractory prostate cancer (HRPC) compared to those patients with localized disease and have been associated with disease progression in other cancer patient population.
- The Cancer and Leukemic Group-B demonstrated that VEGF levels correlate with survival.
Pazopanib is a potent multi-target receptor tyrosine kinase inhibitor of vascular endothelial growth factor receptors.
Detailed Description
VEGF expression is low in all normal prostate tissue, but markedly increased in tumor tissue, and has a positive association with MVD (micro vessel density) tumor stage, grade, and disease-specific survival in patients with prostate cancer. VEGF is known to be under the influence of HIF-1α, which is also up-regulated in the majority of prostate cancer tissue. It has been shown that complete androgen blockade down-regulates VEGF expression via the HIF-1α pathway with concomitant up-regulation of thrombospondin and induction of endothelial cell apoptosis. The VEGF pathway appears to be the dominant vascular formation pathway in prostate cancer with bFGF having a lesser role. Pazopanib , a hydrochloride salt, is a small molecule inhibitor of several tyrosine kinases, ie: VEGF 1, 2, 3, c-KIT and platelet-derived growth factor receptors. The broad blockade of the VEGF receptors should interfere with the VEGF/VEGF-receptor pathway, and have an impact on cell growth. According to the NCCN guidelines , first line therapy for metastatic prostate cancer is considered total androgen blockade, either utilizing orchiectomy and/or LH/RH agonists plus Casodex. Second line therapy would depend on the patient's response to first line therapy, urgency of a response, and the location of metastatic disease. Pazopanib has been explored in several settings. It has recently been looked at with Bicalutamide in hormone refractory prostate cancer. The second study was with earlier disease, i.e. D-0 relapse androgen-sensitive patients. The University of Chicago has a study looking at the sub-population of prostate cancer patients that have a "chemical relapse" in which patients are given one shot of Lupron, and if the PSA is adequately suppressed, the patients are randomized between pazopanib and placebo.
Investigators
James Knost
Principal Investigator
Illinois CancerCare, P.C.
Eligibility Criteria
Inclusion Criteria
- •Diagnosis of adenocarcinoma of the prostate histology, currently on total androgen blockage with a bicalutamide.
- •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 screening window.
- •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.
- •Must have metastatic diagnosis, meaning disease beyond the prostate gland.
- •A progressing PSA of ≥ 3, the PSA will be measured in ≥ 14 days.
- •KPS of ≥ 70
- •Age ≥ 18 years old
- •Adequate organ system functions:
- •Absolute neutrophil count (ANC) ≥ 1.5 X 109/L
- •Hemoglobin ≥ 9 g/dL
Exclusion Criteria
- •Subjects meeting any of the following criteria must not be enrolled in the study:
- •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.
- •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 and,
- •Have no requirement for steroids or enzyme-inducing anticonvulsants (EIAC).
- •Clinically significant gastrointestinal abnormalities including, but not limited to:
- •Malabsorption syndrome,
Arms & Interventions
Advanced prostate cancer, treatment, pazopanib
Pazopanib
Intervention: Pazopanib (GW786034)
Outcomes
Primary Outcomes
Response Rate at 12 Weeks
Time Frame: 12 weeks
Response rate defined as 50% decrease in the Prostate Specific Antigen (PSA) level at week 12 compared to baseline
Secondary Outcomes
- Number Adverse Events, Grades 1-5 Using NCI-CTCAE v 3.0(0-12 weeks)