This study will evaluate the side effects of a fixed dose of vaccine and GM-CSF with
increasing doses of anti-CTLA-4 antibody in patients with advanced prostate cancer. The
vaccine consists of a "priming vaccine" called PROSTVAC/TRICOM, made from vaccinia virus, and
a "boosting vaccine" called PROSTVAC-F/TRICOM, made from fowlpox virus. GM-CSF is a chemical
that boosts the immune system, and anti-CTLA-4 antibody is a protein that may improve
anti-tumor activity and the response to the vaccines. DNA is inserted into the priming and
boosting vaccine viruses to cause production of proteins that enhance immune activity and
also to produce prostate specific antigen (PSA)-a protein that is normally produced by the
patient's tumor cells.
Patients 18 years of age and older with androgen-insensitive prostate cancer that has spread
beyond the original site may be eligible for this 7-month study. Candidates must have disease
that has worsened despite treatments with hormones and up to one chemotherapy regimen. Their
tumor must produce PSA, and they must have no history of allergy to eggs or egg products
Candidates are screened with a medical history and physical examination, blood and urine
tests, electrocardiogram, pathological confirmation of the diagnosis and presence of the PSA
marker, chest x-rays, imaging studies to assess the extent of tumor, and, if clinically
indicated, a cardiologic evaluation.
Participants receive the priming vaccination on study day 1. After 2 weeks and then again
every 4 weeks while on the study, they receive a boosting vaccine. All vaccines are injected
under the skin. On the day of each vaccination and daily for the next 3 days, patients
receive an injection of GM-CSF to increase the number of immune cells at the vaccination
site. On the day of the first six boosting vaccinations, they receive anti-CTLA-4 antibody as
an infusion through a vein over 90 minutes.
Patients are monitored for safety and treatment response with the following tests and
procedures:
- Blood and urine tests monthly, or more often if needed, to monitor liver, kidney, and
other organ function.
- Imaging studies to assess the tumor before starting treatment, again around study days
99 and 183, and then every 3 months after that while on study.
- Apheresis (a procedure for collecting immune cells called lymphocytes) to measure the
immune response to treatment. Apheresis is done three times: before starting the study
and again around study days 99 and 183. For this procedure, blood is collected through a
needle in an arm vein. The blood circulates through a machine that separates it into its
components by spinning, and the lymphocytes are extracted. The rest of the blood is
returned to the patient through the same needle. This will only be done in participants
who have the tissue marker HLA-A2 (about 50% of patients).
Patients whose disease responds to treatment and who do not develop severe side effects may
continue treatment beyond the initial 7-month study period on vaccine alone (without the
antibody). After treatment is completed, patients are monitored for up to 15 years. This
includes a medical history and physical examination for 5 years following the last
vaccination. Information beyond 5 years is collected once a year by telephone.