Phase 1 Trial of Ipilimumab and GVAX in Patients With Metastatic Castration-resistant Prostate Cancer
Ipilimumab, an antibody that blocks cytotoxic T-lymphocyte antigen 4, and GVAX have demonstrated anti-tumor activity in prostate cancer. Pre-clinical studies with this combination have demonstrated potent synergy. The purpose of this study is to investigate, using a phase-I 3+3 dose escalation design followed by an expansion cohort, the safety and efficacy of combined treatment with GVAX and ipilimumab in castration-resistant metastatic prostate cancer (CRPC) patients.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1 Dose Escalation Trial of Ipilimumab in Combination With CG1940 and CG8711 in Patients With Metastatic Hormone-Refractory Prostate Cancer|
- Number of patients with adverse events [ Time Frame: 7 months ] [ Designated as safety issue: Yes ]
- number of patients that have a tumor/PSA response [ Time Frame: 7 months ] [ Designated as safety issue: No ]
- number of patients that will develop a tumor-specific (e.g. PSMA, NY-ESO) antibody response as measured by ELISA [ Time Frame: 7 months ] [ Designated as safety issue: No ]
- the number of patients that have activated T cells and dendritic cells as measured by FACS [ Time Frame: 7 months ] [ Designated as safety issue: No ]
|Study Start Date:||November 2004|
|Study Completion Date:||November 2011|
|Primary Completion Date:||December 2007 (Final data collection date for primary outcome measure)|
|Experimental: Ipilimumab and GVAX||
Drug: GVAX and ipilimumab
All patients receive a 500 million cell priming dose of granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells (GVAX) intradermally on day 1 followed by bi-weekly intradermal injections of 300 million cells for a 24 week period. The vaccinations are combined with monthly intravenous administrations of ipilimumab. The dose-escalation part of this study will be performed using the standard 3+3 phase-I trial design. Patients will be enrolled in cohorts of three; each cohort will receive an escalating dose of ipilimumab at 0•3, 1•0, 3•0 or 5•0 mg/kg. Sixteen patients will be treated in an expansion cohort with GVAX and 3•0 mg/kg ipilimumab.
A promising immunotherapeutic approach in prostate cancer is whole-cell vaccination. Irradiated allogeneic tumor cells expressing GM-CSF generate a long-lasting and specific anti-tumor immunity in preclinical models. Results from several phase I and II trials showed Prostate GVAX (GVAX) to be well tolerated and suggested improved survival. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is a crucial immune checkpoint molecule that down-regulates T-cell activation and proliferation. Ipilimumab, a fully human monoclonal antibody (IgG1) that blocks CTLA-4, promotes antitumor immunity, and has been demonstrated in two phase III trials to improve overall survival in metastatic melanoma patients. Pre-clinical studies of the anti-CTLA-4 antibody in combination with GM-CSF secreting tumor cell vaccines demonstrated a potent synergy. In this phase I study the investigators examine in CRPC patients whether ipilimumab can be safely combined with GVAX. In addition, the investigators will treat an additional 16 patients at a dose level of 3•0 mg/kg to determine the safety profile and antitumor effects of GVAX and ipilimumab in patients with CRPC.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01510288
|VU university medical center|
|Amsterdam, Netherlands, 1081 HV|
|Principal Investigator:||Winald Gerritsen, Prof. MD PhD||VU University Medical Center|
|Principal Investigator:||Fons van den Eertwegh, MD PhD||VU University Medical Center|