A Randomized Phase II Trial Combining Vaccine Therapy With PROSTVAC/TRICOM and Flutamide vs. Flutamide Alone in Men With Androgen Insensitive, Non-Metastatic (D0.5) Prostate Cancer
- There is no standard of care for prostate cancer patients progressing on hormone
therapy with a rising serum PSA 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.
- 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.
- To determine preliminary evidence of any patterns of immunologic effects which differ
by treatment including the immunologic effects of flutmaide withdrawal on patients
continuing on vaccine following a rising PSA on flutamide.
- 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 scan or
- Hgb 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 and ALT less than 2.5
times upper limit of normal
-Flutamide will be administered at a dose of 250 mg PO tid every day in both arms A and B.
rV-PSATRICOM will be administered s.c. on day 1 in Arm B.
rF-PSATRICOM will be administered s.c. on day 29 & every 4 weeks in Arm B.
- Sargramostim 100 microg s.c. will be given at the vaccine site for 4 consecutive days
starting on day 1 of each vaccine only for patients enrolled at the NCI site.
- 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
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Time to treatment failure
Ravi A Madan, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|
|Cancer Institute of New Jersey||New Brunswick, New Jersey 08901|