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Sponsors and Collaborators: |
National Center for Research Resources (NCRR) Duke University |
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Information provided by: | National Center for Research Resources (NCRR) |
ClinicalTrials.gov Identifier: | NCT00006430 |
Purpose: This protocol proposes a safety and feasibility trial in patients with metastatic prostate cancer (stages D1-D3) investigating the induction of antitumor immunity by administration of cultured autologous peripheral blood precursor derived dendritic cells (DC), transfected with mRNA amplified from autologous prostate tumor tissue. The feasibility and dose-limiting toxicity of administering escalating doses of tumor RNA transfected dendritic cells will be defined. As a secondary endpoint, the ability of tumor RNA transfected dendritic cells to induce tumor-specific immune responses will be evaluated. Finally, the anti-tumor effect based on PSA (biochemical) response criteria will be defined.
Background: Because prostate cancer is incurable when metastatic and conventional therapies do not offer a clear survival benefit, new therapeutic strategies are warranted. This study is based on the premise that clinically effective cell mediated immune responses against prostate tumors can be elicited by activation of tumor associated antigen specific T cells. Work performed by others and our group suggests that PSA, a protein expressed in virtually all prostate cancers, can serve as a widely expressed candidate antigen for prostate cancer immunotherapy. In particular, we have shown that cultured dendritic cells transfected with mRNA encoding PSA are remarkably effective in stimulating antigen specific immunity in vitro. Therefore, we hypothesize that administration of PSA RNA transfected DC will lead to detectable levels of PSA specific CTL in the peripheral blood of patients with PSA expressing metastatic prostate cancer. It is hoped that these T cell responses also have clinical antitumor activity.
Condition | Intervention | Phase |
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Prostate Cancer |
Biological: Autologous dendritic cells transfected with amplified tumor RNA |
Phase I |
Study Type: | Interventional |
Study Design: | Treatment |
Methods: Patients will undergo percutaneous needle biopsies from either primary or metastatic sites to obtain tumor tissue. Patients in whom sufficient tumor mRNA has been amplified by PCR to transfect the assigned dendritic cell dose will undergo leukapheresis and peripheral blood mononuclear cells will be cultured in vitro for 7 days with GM-CSF and IL-4 to generate precursor derived dendritic cells. Dendritic cells will then be cryopreserved for later use. On the day the patient returns to receive his infusion (weeks 0, 2, and 4) the dendritic cells will be thawed, reconstituted, and transfected with amplified total tumor mRNA. Patients will receive a total of 3 treatments consisting of combined I.V. and I.D. injections, each on study week 0, 2, and 4.
Repeat leukapheresis will be performed 2 weeks after the last dose to determine immune function. PSA levels will be measured prior to the start of treatment and 2 weeks following the last infusion. Patients who do not receive therapy due to a failure to produce sufficient RNA or dendritic cells will be replaced in order to assess toxicity.
Data Analysis: 1. To determine the short and long term toxicities associated with administration of tumor RNA dendritic cells in patients with metastatic prostate cancer. 2. To determine feasibility of dendritic cell vaccine generation according to the proportion of patients for whom sufficient cells are generated to provide treatment. 3. To determine the cellular immune response to intravenous infusion of tumor RNA dendritic cells.
4. To measure the PSA response of patients with metastatic prostate cancer to intravenous infusion of tumor RNA dendritic cells.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Male |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Patients must have recovered from all acute toxicities from prior treatment.
United States, North Carolina | |
Duke University Medical Center | |
Durham, North Carolina, United States, 27710 |
Principal Investigator: | Johannes Vieweg, M.D. | Duke University |
Study ID Numbers: | NCRR-M01RR00030-0177, M01RR00030 |
Study First Received: | November 3, 2000 |
Last Updated: | June 23, 2005 |
ClinicalTrials.gov Identifier: | NCT00006430 History of Changes |
Health Authority: | United States: Federal Government |
Prostatic Diseases Genital Neoplasms, Male Urogenital Neoplasms |
Genital Diseases, Male Prostatic Neoplasms Carcinoma |
Neoplasms Neoplasms by Site Prostatic Diseases Genital Neoplasms, Male |
Urogenital Neoplasms Genital Diseases, Male Prostatic Neoplasms |