GVAX in Advanced Prostate Cancer Patients Made Lymphopenic
Androgen (a male sex hormone) deprivation is the standard therapy for metastatic prostate cancer and results in regression or control of disease in 80-85% of patients. This hormone therapy results in a progression-free survival of 12-18 months and overall survival of 24-30 months. However, all patients ultimately develop hormone-refractory prostate cancer (HRPC). Management of HRPC patients is a significant challenge for both patient and physician. Neither past nor current chemotherapy regimens have shown curative potential in patients with HRPC. Thus new treatment strategies are a high priority.
A major focus of new treatment strategies is to enlist the aid of the immune system, particularly the development of prostate cancer vaccines. There has been a number of studies using dendritic cell based vaccines and the treatment has been well tolerated. Specific T-cell immune responses have been observed and occasional evidence for tumor regression. A reduction in serum prostate-specific antigen (PSA) has been observed as well. Lengthening the time-to-progression and delays in the onset of bone pain have been observed in subsets of patients with HRPC.
The initial preclinical observations suggesting that a granulocyte-macrophage colony-stimulating factor (GM-CSF) gene transduced allogeneic (GVAX) prostate cancer vaccine may be efficacious in poorly immunogenic cancers were reported.
The objective of this study is to evaluate the safety and immunologic effects of vaccinations with Allogeneic Prostate GVAX® (CG1940 & CG8711) in patients made lymphopenic by treatment with chemotherapy and infused with autologous peripheral blood mononuclear cells (PBMC). Clinical observations and laboratory measurements will be monitored to evaluate safety, toxicity and immune responses. Additionally, the effects of treatment on serum PSA levels and tumor response will be evaluated.
Biological: GM-CSF gene transduced allogeneic vaccine GVAX
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of Human GM-CSF Gene-Transduced Irradiated Prostate Allogeneic Cancer Cell Vaccines (GVAX®) in Advanced Prostate Cancer Patients Made Lymphopenic and Infused With Autologous Peripheral Blood Mononuclear Cells|
- To evaluate the safety of combined CG1940 & CG8711, chemotherapy with cyclophosphamide +/- fludarabine and hematopoietic reconstitution in patients with advanced hormone-refractory prostate cancer (HRPC)
- To explore the effects of different chemotherapy regimens on the immune response of CG1940 & CG8711 vaccinated and reconstituted lymphopenic patients with HRPC
- To compare the frequency of tumor vaccine-specific, PSMA-specific T cells, and the titer of vaccine-specific antibodies in Cohorts A-C, compare in Cohorts A-C
- To evaluate in vitro sensitization (IVS) methods for their capacity to expand tumor vaccine-specific CD4+ and CD8+ T cells from the peripheral blood
- To determine whether the degree of lymphopenia inversely correlates with the expansion of tumor-specific CD4 and CD8 T cells
- To evaluate the effects of these procedures on serum PSA levels and tumor response
|Study Start Date:||July 2005|
|Estimated Study Completion Date:||July 2005|
Please refer to this study by its ClinicalTrials.gov identifier: NCT00122005
|United States, Oregon|
|Providence Portland Medical Center|
|Portland, Oregon, United States, 97213|
|Principal Investigator:||Bernard Fox, PhD||Providence Health & Services|