A Phase I Study of Sequential Vaccinations With Fowlpox-CEA(6D)-Tricom (B7.1/ICAM/LFA3) and Vaccinia-CEA (6D)-Tricom, in Combination With GM-CSF and Interferon-Alfa-2B in Patients With CEA-Expressing Carcinomas
I. Determine the maximum tolerated dose and recommended phase II dose of interferon alfa-2b
(IFN-α-2b) when administered with recombinant vaccinia-CEA(6D)-TRICOM vaccine, recombinant
fowlpox-CEA(6D)-TRICOM vaccine, and sargramostim (GM-CSF) in patients with locally advanced
or metastatic carcinoembryonic antigen (CEA)-expressing carcinoma.
I. Determine the effect of IFN-α-2b on tumor cell expression of CEA and MHC class I antigens
in patients treated with this regimen.
II. Determine the immunologic effects of this regimen in these patients. III. Determine any
objective anti-tumor responses that may occur in response to this regimen in these patients.
IV. Determine the time to tumor progression in patients treated with this regimen.
OUTLINE: This is a dose-escalation study of interferon alfa-2b (IFN-α-2b).
COURSE I: Patients receive recombinant vaccinia-CEA(6D)-TRICOM vaccine subcutaneously (SC)
on day 1. Patients also receive sargramostim (GM-CSF) SC on days 1-4 and IFN-α-2b* SC on
days 9, 11, and 13.
COURSES II-IV: Patients receive recombinant fowlpox-CEA(6D)-TRICOM vaccine SC on day 1.
Patients also receive GM-CSF as in course 1 and IFN-α-2b* SC on days 1, 3, and 5.
NOTE: *The initial cohort of 6 patients does not receive IFN-α-2b.
Treatment repeats every 28 days for 4 courses in the absence of disease progression or
unacceptable toxicity. After 4 courses, patients who do not have progressive disease or
unacceptable toxicity may receive recombinant fowlpox-CEA (6D)-TRICOM vaccine, GM-CSF, and
IFN-α-2b every 28 days for 2 more courses and then every 3 months for up to 2 years.
Cohorts of 3-6 patients receive escalating doses of IFN-α-2b until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity. Six additional patients are treated at the
MTD; these patients must be HLA-A2 positive.
After completion of study treatment, patients are followed monthly for 4 months and then
every 6-12 months for up to 15 years.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of IFN-alpha-2b, defined as the dose level one level beneath that dose at which 2 or more of 6 patients showed DLT, graded according to NCI CTCAE version 4.0
Up to 112 days
Ohio State University
United States: Food and Drug Administration
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