A PHASE I TRIAL OF RECOMBINANT VACCINIA VIRUS THAT EXPRESSES PSA IN PATIENTS WITH ADENOCARCINOMA OF THE PROSTATE
I. Assess the toxicity associated with repeated vaccination with recombinant vaccinia virus
expressing prostate-specific antigen (rV-PSA) in patients with metastatic adenocarcinoma of
II. Determine the optimal dose of rV-PSA given at monthly intervals based on cellular and
III. Determine whether vaccination with rV-PSA is associated with anti-tumor activity.
IV. Determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF) has an
effect on cellular and humoral immunity different from rV-PSA, and whether the addition of
GM-CSF has enhanced antitumor effect compared to rV-PSA alone.
OUTLINE: This is an open label, dose escalation study.
Patients in cohorts of 3-6 receive 3 vaccinations with rV-PSA at 4-week intervals (days 1,
29, 57, and 85) in the absence of disease progression or unacceptable toxicity. Response
assessment is performed at eight weeks. Patients who discontinue therapy prior to eight
weeks are considered unevaluable for response. If dose limiting toxicity is observed in 2 of
6 patients entered at a dose level, no further patients are entered at that level and the
MTD is defined as the preceding dose level. Ten additional patients are treated at the MTD
and receive granulocyte-macrophage colony-stimulating factor (GM-CSF) administered
subcutaneously on day -1 through day 2 of each cycle. Patients who are HLA-A2 positive, have
received all 3 rV-PSA vaccinations without unacceptable toxicity, and have been off study
for at least 30 days due to disease progression may continue treatment with rV-PSA at the
highest dose level and the addition of GM-CSF.
Patients are followed monthly for 6 months.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Donald W. Kufe, MD
Dana-Farber Cancer Institute
United States: Food and Drug Administration
|Massachusetts General Hospital Cancer Center||Boston, Massachusetts 02114|
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|Brigham and Women's Hospital||Boston, Massachusetts 02115|