Background:
* There is no standard of care for prostate cancer patients progressing on hormone therapy with a rising serum PSA (prostatic specific antigen) level without evidence of metastatic disease.
* We have completed a phase II trial in which men with this stage of disease were randomized to receive a pox vector PSA vaccine vs. the antiandrogen nilutamide.
* The median time to treatment failure on nilutamide was 7.6 months.
* 12 patients on the vaccine arm had nilutamide added at the time of PSA progression.
* The median time for treatment failure after the addition of nilutamide was 13.9 months, for a total of 25.9 months from initiation of vaccine therapy.
* This suggests that the combination of hormone therapy with vaccine therapy may lead to an improved clinical benefit compared to hormone therapy alone.
* Due to the increased toxicity of nilutamide compared to other antiandrogens and the patients prior exposure to bicalutamide therapy, we plan to use flutamide as a second line hormonal manipulation in the below study.
Objectives (Primary):
-To determine if use of a combination of vaccine plus flutamide may be associated with a trend toward improvement in time to treatment failure compared to flutamide alone.
Eligibility:
* Must have non metastatic androgen insensitive prostate cancer with a rising PSA with castrate levels of testosterone and no evidence of metastatic disease on CT (computed tomography) scan or bone scan.
* Hgb (hemoglobin) greater than or equal to 9 g/dL.
* Lymphocyte count greater than or equal to 500/mm(3).
* Hepatic function: Bilirubin less than or equal to 1.5 mg/dL, OR patients with Gilbert's syndrome, a total bilirubin less than or equal to 3.0 mg/dL, AST (aspartate aminotransferase) and ALT (alanine aminotransferase) less than 2.5 times upper limit of normal
Design:
-Flutamide will be administered at a dose of 250 mg PO (by mouth) tid (three times a day) every day in both arms A and B.
rV-PSATRICOM will be administered s.c. (subcutaneous) on day 1 in Arm B.
rF-PSATRICOM will be administered s.c. on day 29 \& every 4 weeks in Arm B.
* For patients with declining PSA no restaging will be done unless they develop symptoms consistent with metastatic disease.
* For patients with rising PSA, once 2 consecutive PSA rises are seen, a CT will be done at their next scheduled visit. They will then be re-staged (CT and bone scans) at 3 month intervals as long as PSA continues to rise.
* After 3 months of therapy, patients receiving the flutamide alone (arm A) may cross over to receive vaccine if they develop a rising PSA and scans are without metastatic disease. The vaccine may commence 4 weeks after flutamide is stopped if the PSA continues to rise. If there is an antiandrogen withdrawal response (a decline in PSA 28 days after the discontinuation of flutamide), PSA serum levels will be checked every 28 days and vaccine may commence when the serum PSA levels begin to rise (if scans are negative for metastatsis). Patients on arm B will have flutamide discontinued and may continue vaccine therapy. At this point patients may continue to receive treatment on study until the development of disease on scans or a second occurrence of clinical progression.
* Patients who have been on study for 2 years or more with stable disease and who are not getting vaccine, clinic visits may be scheduled every 8 weeks. (Patients receiving monthly vaccine will continue to have monthly visits.)
* For patients who have stable disease and attend clinic every 8 weeks, once 2 consecutive PSA rises are seen, a CT and bone scan will be done at their next visit in 4 weeks. They will then be restaged (CT and bone scans) at 3 month intervals as long as PSA continues to rise.
