A Pilot Study of Sequential Vaccinations With ALVAC-CEA and Vaccinia-CEA With the Addition of IL-2 and GM-CSF in Patients With CEA Expressing Tumors
OBJECTIVES: I. Evaluate the safety of sequentially administered vaccinia-carcinoembryonic
antigen (CEA) vaccine and ALVAC-CEA vaccine (CEA-Avipox vaccine) in two schedules and with
the addition of sargramostim (GM-CSF) plus or minus interleukin-2 (IL-2) in patients with
CEA expressing tumors. II. Compare the CEA-specific cellular immune response in cancer
patients randomized to receive a single vaccination with vaccinia-CEA vaccine followed by
three boosts with ALVAC-CEA vaccine (V-A-A-A) or the reverse vaccination sequence (A-A-A-V).
III. Determine whether the addition of GM-CSF alone or with IL-2 enhances the immune
response to sequentially administered vaccinia-CEA vaccine and ALVAC-CEA vaccine. IV.
Compare the enzyme linked immunosorbent assay ELISPOT with lymphoproliferative and
cytotoxicity assays for measuring CEA-specific T lymphocyte immune response.
OUTLINE: This is two-stage, partially randomized study. In stage one, patients are
randomized to arm I or II. Arm I: Patients receive vaccinia-carcinoembryonic antigen (CEA)
vaccine intradermally on day 1 of course 1 and ALVAC-CEA vaccine (CEA-Avipox vaccine)
intramuscularly (IM) on day 1 of courses 2-4. Each course lasts 28 days. Arm II: Patients
receive ALVAC-CEA vaccine (CEA-Avipox vaccine) IM on day 1 of courses 1-3 and vaccinia-CEA
vaccine intradermally on day 1 of course 4. Each course lasts 28 days. Patients in arms I
and II continue 28-day courses through month 6 and then receive 3-month courses for 2 years
in the absence of disease progression or unacceptable toxicity. In stage two, patients are
enrolled successively into arms III and IV. Arm III: Patients receive vaccines according to
whichever schedule (arm I or II) was found to be superior plus sargramostim (GM-CSF)
subcutaneously (SC) on days 1-4 of each course. Each course lasts 28 days. Arm IV: Patients
receive vaccines plus GM-CSF as in arm III and interleukin-2 SC once daily on days 7-11 of
each course. Each course lasts 28 days. Patients on arms III and IV continue 28-day courses
through month 6 and then receive 3-month courses for 2 years in the absence of disease
progression or unacceptable toxicity. If 2 or more patients in either arm III or IV
experience dose limiting toxicity, accrual into study stops. Otherwise, the best response
among the 4 arms is determined and further HLA-A2 positive patients are enrolled into that
arm so that a total of 6 HLA-A2 positive patients with advanced disease and 6 HLA-A2
positive patients with NED (without radiographic or clinical evidence of tumor) are treated.
If more than one regimen is equally superior, the least toxic regimen is chosen for further
accrual. Patients are followed at 28 days following the last vaccination.
PROJECTED ACCRUAL: A minimum of 24 patients (6 HLA-A2 positive and up to 3 HLA-A2 negative
patients per arm) will be accrued for this study.
Allocation: Randomized, Primary Purpose: Treatment
John L. Marshall, MD
Lombardi Cancer Research Center
United States: Federal Government
|National Naval Medical Center||Bethesda, Maryland 20889|
|Lombardi Cancer Center, Georgetown University||Washington, District of Columbia 20007|