A Phase I Study of Sequential Vaccinations With Fowlpox-CEA(6D)-TRICOM (B7.1/ICAM/LFA-3) Alone, and in Combination With Vaccinia-CEA(6D)-TRICOM, and the Role of GM-CSF, in Patients With CEA Expressing Carcinomas
I. To determine the maximum tolerated dose and toxicity profile of the novel CEA-based
vaccine, rF-CEA(6D)-TRICOM (recombinant fowlpox-CEA(6D)-B7.1/ICAM-1/LFA-3), either alone or
in combination with a second vaccine, rV-CEA(6D)-TRICOM (recombinant
vaccinia-CEA(6D)-B7.1/ICAM-1/LFA-3) in patients with advanced CEA-bearing cancers.
II. To determine the maximum tolerated dose and toxicity profile of the novel CEA-based
vaccine rV-CEA(6D)-TRICOM when given in combination with the maximum tolerated dose of
rF-CEA(6D)-TRICOM, in patients with advanced CEA-bearing cancers.
III. To determine the safety and impact of colony stimulating factors (GM-CSF) on the
immunologic response, when given in conjunction with the combination of rV-CEA(6D)-TRICOM
(MTD) and rF-CEA(6D)-TRICOM (MTD) vaccines, in patients with advanced CEA-bearing cancers.
IV. To determine the change in CAP-1 directed T cells in patients treated with these
vaccines using ELISPOT assay analysis.
V. To perform a pilot analysis of the impact of vaccine therapy on the quantity of
circulating CEA-positive cells in the patients treated on this study in order to develop and
eventually validate a practical, intermediate bio-marker for the immunologic response to the
VI. To document any objective anti-tumor responses that occur.
OUTLINE: This is a dose-escalation study of fowlpox-CEA-TRICOM (fCEA-TRI) vaccine and
vaccinia-CEA-TRICOM (vCEA-TRI) vaccine.
STAGE I: Patients receive fCEA-TRI vaccine subcutaneously (SC) once daily on days 1, 29, 57,
Cohorts of 3-10 patients receive escalating doses of the fCEA-TRI vaccine until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2
of 6 patients experience dose-limiting toxicity (DLT).
STAGE II: Patients receive vCEA-TRI vaccine intradermally once on day 1 and fCEA-TRI vaccine
SC at the MTD determined in stage I once daily on days 29, 57, and 85.
Cohorts of 3-10 patients receive escalating doses of the vCEA-TRI vaccine until the MTD is
determined. The MTD is defined as the dose preceding that at which 2 of 6 patients
STAGE III: A single cohort of 6-10 patients receive both vaccines as in stage II, at the
MTDs determined in stages I and II, and sargramostim (GM-CSF) SC once daily on days 1-4,
29-32, 57-60, and 85-88.
Patients in any stage of the study with responding disease may receive additional doses of
the fCEA-TRI vaccine monthly for 2 months and then every 3 months thereafter. Patients who
have objective evidence of response (including mixed response) and/or a fall in an elevated
serum CEA level after the sixth vaccine and who subsequently develop disease progression
while on the extended every 3-month treatment schedule and have no other potentially better
treatment alternatives available may continue treatment as per the monthly vaccination
schedule for 2 additional months. Patients with stable or responding disease after those two
monthly vaccines may continue monthly vaccines at the discretion of the principal
Patients are followed at 4 weeks and then monthly for 3 months.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Immunologic response, measured by the frequency of interferon gamma-releasing T cells specific to CAP-1, an HLA-A2 restricted epitope of CEA, as measured by the ELISPOT assay
Pre and post-vaccination CTL precursor frequencies will be calculated so that changes in CTL precursor frequencies can be compared between dose levels of the vaccine. Also, 95% confidence intervals can be calculated for the percent increases (or decreases) in CTL precursor frequencies between dose levels.
Up to 3 months after completion of study treatment
Lombardi Comprehensive Cancer Center at Georgetown University
United States: Food and Drug Administration
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