NCT01510288

Phase 1 Trial of Ipilimumab and GVAX in Patients With Metastatic Castration-resistant Prostate Cancer

A Phase 1 Dose Escalation Trial of Ipilimumab in Combination With CG1940 and CG8711 in Patients With Metastatic Hormone-Refractory Prostate Cancer

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: Amsterdam UMC, location VUmc · Academic / Other
• Sex: Male
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Prostate Cancer

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2004-11-01
• Primary completion: 2007-12-01
• Completion: 2011-11-01
• First posted: 2012-01-16
• Last updated: 2012-01-16

Locations

1 site across 1 country: Netherlands