Phase I Study of a Recombinant Fowl Pox Vaccine rF-CEA (6D)/TRICOM Alone or With GM-CSF in Patients With Advanced CEA Expressing Adenocarinomas
I. Determine the toxicity of recombinant fowlpox-CEA-TRICOM vaccine with or without
sargramostim (GM-CSF) or recombinant fowlpox-GM-CSF in patients with advanced or metastatic
II. Determine the CEA-specific T-cell precursor frequency in patients treated with these
III. Assess the immunogenicity of GM-CSF in patients treated with these regimens.
IV. Determine the inflammatory response and cytokine expression at the vaccination site in
these patients 48 hours after vaccination.
V. Correlate telomere length of leukocytes with prior cytotoxic therapies and immunologic
response in patients treated with these regimens.
OUTLINE: This is a dose-escalation study. The first three cohorts of 3-12 patients receive
escalating doses of recombinant fowlpox-CEA-TRICOM vaccine (fCEA-TRI) until the maximum
tolerated dose (MTD) is determined.
The MTD is defined as the dose preceding that at which 2 of 6 patients or 3 of 12 patients
experience dose-limiting toxicity. fCEA-TRI is administered intradermally every 2 weeks for
4 doses and then every 2 months thereafter (beginning on day 56) in the absence of disease
progression or unacceptable toxicity.
The fourth and fifth cohorts of 6 patients receive fCEA-TRI at the MTD in the same manner as
the first three cohorts combined with escalating doses of sargramostim (GM-CSF). GM-CSF is
administered subcutaneously once daily beginning on the day of each vaccination and
continuing for a total of 4 days.
The sixth through eighth cohorts of 6 patients receive fCEA-TRI at the MTD in the same
manner as the first three cohorts combined with escalating doses of recombinant
fowlpox-GM-CSF (rF-GM-CSF). rF-GM-CSF is administered in the same manner as GM-CSF.
Patients are followed every month for 4 months.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of recombinant fowlpox-CEA(6D)/TRICOM vaccine determined by dose-limiting toxicities graded according to NCI Common Toxicity Criteria, version 2.0
Margaret von Mehren
Fox Chase Cancer Center
United States: Food and Drug Administration
|Fox Chase Cancer Center||Philadelphia, Pennsylvania 19111|