A Phase II Randomized Trial of Recombinant Fowlpox and Recombinant Vaccinia Virus Expressing PSA in Patients With Adenocarcinoma of the Prostate
I. Determine the toxicity and maximum tolerated dose of recombinant fowlpox
prostate-specific antigen (PSA) vaccine in patients with advanced adenocarcinoma of the
II. Determine whether vaccination with recombinant fowlpox-PSA vaccine is associated with
antitumor activity in these patients.
III. Determine the efficacy of prime and boost regimens using recombinant fowlpox-PSA
vaccine and recombinant vaccinia-PSA vaccine in these patients.
IV. Compare the PSA-specific T-cell response in patients treated with recombinant
fowlpox-PSA vaccine followed by recombinant vaccinia-PSA vaccine vs the same vaccines but in
OUTLINE: This is a randomized, open-label, multicenter, dose-escalation study of recombinant
fowlpox prostate-specific antigen (PSA) vaccine.
SAFETY COHORT: The first cohort of 3 patients receives vaccination with recombinant
fowlpox-PSA vaccine intramuscularly (IM). Treatment repeats every 4 weeks for 3 courses. In
the absence of unacceptable toxicity in the first cohort, the second cohort of 3 patients
receives the same vaccine at the dose level immediately higher than the first cohort dose
level. In the presence of unacceptable toxicity in the first cohort, the second cohort of 3
patients receives the same vaccine at a dose level lower than the first cohort dose level.
The maximum tolerated dose (MTD) is the dose preceding that at which 1 of 6 patients
experiences grade 3 or worse dose-limiting toxicity.
Subsequent patients are assigned to one of two vaccination groups based on prior treatment
with recombinant vaccinia-PSA vaccine:
GROUP A (no prior recombinant vaccinia-PSA vaccine): Patients are randomized to one of two
ARM I: Patients receive recombinant fowlpox-PSA vaccine IM at the MTD from the safety cohort
every 4 weeks for 3 courses. Patients then receive recombinant vaccinia-PSA vaccine
intradermally every 4 weeks for 2 courses.
ARM II: Patients receive the same vaccines as in arm I but in reverse order.
GROUP B (prior recombinant vaccinia-PSA vaccine): Patients receive treatment as in arm I,
GROUPS A AND B: Patients with stable or responding disease at 6 months after completion of
vaccination therapy may continue treatment on the group and arm to which they were
originally assigned. Treatment repeats every 6-9 months in the absence of disease
Patients are followed monthly for 6 months and then every 3 months thereafter.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
PSA response is assessed at 3 successive monthly determinations, starting 28 days after the final vaccine dose.
Up to 3 months after the final vaccine dose
Joseph Paul Eder
Dana-Farber Cancer Institute
United States: Food and Drug Administration
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|