Phase I Trial of a PSA Based Vaccine and an Anti-CTLA-4 Antibody in Adults With Metastatic Androgen Independent Prostrate Cancer
- Adenocarcinoma of the prostate is the most common cancer diagnosis in American males,
and the second leading cause of cancer death.
- The proposed vaccine strategy represents a third-generation design that elicits a
T-cell immune response to cells expressing PSA and has been shown to break tolerance to
this self-antigen, and cause objective response and PSA declines in patients with
- This strategy also utilizes an antibody to CTLA-4 that may block the normal signals to
down regulate the immune response following active vaccination.
- Anti CTLA-4 antibodies have been associated with autoimmune events that are generally
manageable and have been associated with clinical response.
- To determine the safety and tolerability of a combination of a fixed dose of vaccine
and anti-CTLA4, which will be dose escalated.
- To evaluate immunologic response (as measured by an increase in PSA specific T-cells
measured by ELISPOT in HLA-A2+ patients), and clinical response (as measured by RECIST
and PSA consensus criteria).
- Must have metastatic androgen insensitive prostate cancer with no bone pain requiring
narcotics and have had no more prior chemotherapy.
- Life expectancy greater than or equal to 6 months. ECOG 0-1
- Should have no autoimmune diseases; no evidence of being immunocompromised; no serious
intercurrent medical illness; no cardiac disease; no prior splenectomy.
- No prior treatment with MDX-010 (Ipilimumab).
- No brain metastasis, history of seizures, encephalitis, or multiple sclerosis.
- No serious hypersensitivity reaction to egg products.
- This is an open label, phase I safety trial with sequential cohorts of patients all
receiving a fixed dose of PSA-TRICOM vaccines and sargramostim, with dose escalation of
- PROSTVAC -V/TRICOM (vaccinia) 2 x 10(8) pfu subcutaneously will be administered as the
initial priming vaccine on day 1 of cycle 1 only.
- PROSTVAC -F/TRICOM (fowlpox) 1 x 10(9) pfu subcutaneously starting on day 15 followed
by monthly boosting vaccination. Sargramostim 100 mcg per day will be administered
subcutaneously at the vaccination site on days 1-4 of each vaccine cycle (prime and
- MDX-010 (Ipilimumab) will be administered, as per the assigned dose level, as a
90-minute intravenous infusion on the same day as the monthly boosting vaccinations
with PROSTVAC-F/TRICOM (fowlpox). After 6 courses of MDX-010, patients may receive
Maintenance dose of MDX-010 every 3 months until there is evidence of disease
progression or toxicity, for up to an additional 12 months (equivalent to 4 additional
- Monthly boosting vaccinations with PROSTVAC-F/TRICOM (fowlpox) and sargramostim may
then continue until patients meet off study criteria.
Primary Purpose: Treatment
To determine the safety and tolerability of a combination of a fixed dose of vaccine and anti-CTLA4, which will be dose escalated.
Rohan Hazra, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|