Recombinant fowlpox-TRICOM vaccine(NCI)

Background:
No treatment is known to improve survival for prostate cancer patients who have not been helped by previous treatments with hormones and chemotherapy.
An experimental vaccine called prostate specific antigen (PSA)/TRICOM contains genes for a protein produced by prostate cancer cells called prostate-specific antigen (PSA). The vaccine can trigger the immune system to make cells that may be able to recognize and attack the cancer cells that make PSA.
Granulocyte macrophage colony stimulating factor (GM-CSF) is an approved drug that is usually given to increase a patient's white blood cell count or to stimulate the immune system.
1Samarium-153-ethylene diamine tetramethylene phosphonate (53Sm-EDTMP) is a radioactive drug that has been approved for many years to treat advanced prostate cancer. It is given through a vein and can be targeted directly to tumors in the bone where it can relieve pain caused by bone lesions. Radiation also increases the level of certain proteins inside the tumor, making it easier for the immune system to find and kill the tumor cells.
When laboratory mice were given just vaccine, just radiation, or a combination of both, the combination was most effective in treating tumors.
Objectives:
-To determine if combined treatment with PSA/TRICOM vaccine and 153Sm-EDTMP radiation can delay progression of prostate cancer better than radiation alone.
Eligibility:
-Patients who have advanced prostate cancer that has worsened despite treatments with hormones, have two or more bone lesions related to their prostate cancer, and have had prior treatment with docetaxel chemotherapy.
Design:
Patients are randomly assigned to receive radiation alone (Arm A) or radiation with vaccine and sargramostim (Arm B).
Arm A receives 153Sm-EDTMP radiation starting on study day 8 and repeated every 12 weeks.
Arm B receives a priming vaccine on study day 1 and radiation on day 8. Radiation therapy is repeated every 12 weeks. Boosting vaccines are given on days 15 and 29 and then monthly. GM-CSF is given with each vaccination (on the day of the vaccination and for the next 3 days) to enhance the immune response. Vaccinations and GM-CSF are given as injections under the skin, usually in the thigh. Radiation therapy is given through a vein.
Patients are monitored regularly with physical examinations, blood and urine tests, and scans to evaluate safety and treatment response.
Patients who are human leukocyte antigen serotype within HLA-A A serotype group (HLA-A2)-positive undergo apheresis, a procedure similar to donating blood, for obtaining immune cells called lymphocytes to measure the immune response to the vaccine.

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.