Randomized Single Institution Pilot Study of Vaccinia-CEA (6D)-Tricomand Fowlpox CEA(6D)-Tricom With GM-CSF in Combination With Docetaxel in Patients With CEA-Bearing Cancers
- Determine the recommended dose and schedule of docetaxel when given in combination with
recombinant vaccinia-CEA-TRICOM vaccine, recombinant fowlpox-CEA-TRICOM vaccine, and
sargramostim (GM-CSF), defined by best immune response with acceptable toxicity, in
patients with carcinoembryonic antigen (CEA)-expressing metastatic lung or colorectal
- Compare the effect of varying doses and schedules of docetaxel on CEA-specific T-cell
immune responses by ELISPOT assay in patients treated with these regimens.
- Compare objective antitumor response in patients treated with these regimens.
OUTLINE: This is a 2-part, randomized, pilot study. Patients are randomized to 1 of 6
treatment arms: arms I, II, and III in part I (lung cancer and colorectal cancer patients)
and arms IV, V, and VI in part II (lung cancer patients only). Patients are stratified
according to disease site and HLA-A2 positivity (positive vs negative). At least 6 of 10
patients must be HLA-A2 positive for each of the treatment arms.
- Vaccinia-CEA-TRICOM vaccine (parts I and II): In all treatment arms, patients receive
vaccinia-CEA-TRICOM vaccine intradermally on day 1 and sargramostim (GM-CSF)
subcutaneously (SC) into the vaccine site on days 1-4.
- Fowlpox-CEA-TRICOM vaccine and concurrent chemotherapy:
- Part I (lung cancer and colorectal cancer patients):
- Arm I: Three weeks after treatment with vaccinia-CEA-TRICOM vaccine, patients
receive fowlpox-CEA-TRICOM vaccine SC on day 1 and GM-CSF SC into each
vaccination site on days 1-4.
- Arm II: Patients receive fowlpox-CEA-TRICOM vaccine and GM-CSF as as in arm I
and lower-dose docetaxel IV over 30 minutes on days 1 and 8.
- Arm III: Patients receive fowlpox-CEA-TRICOM vaccine and GM-CSF as in arm I
and standard-dose docetaxel IV over 30 minutes on days 1 and 8.
- Part II (lung cancer patients only):
- Arm IV: Patients receive fowlpox-CEA-TRICOM vaccine and GM-CSF as in arm I
and full-dose docetaxel IV over 1 hour on day 1.
- Arm V: Patients receive full-dose docetaxel IV over 1 hour on day 1,
fowlpox-CEA-TRICOM vaccine SC on day 8, and GM-CSF SC into each vaccination
site on days 8-11.
- Arm VI: Patients receive full-dose docetaxel as in arm V, fowlpox-CEA-TRICOM
vaccine SC on day 15, and GM-CSF SC into each vaccination site on days 15-18.
Treatment in all arms repeats every 21 days for a total of 4 courses in the absence of
disease progression or unacceptable toxicity. Patients who do not have significant disease
progression or unacceptable toxicity after 4 courses of treatment may receive additional
fowlpox-CEA-TRICOM vaccine and docetaxel according to the treatment arm on which they were
enrolled at study entry.
Patients are followed every 6 months for 2 years and then annually for 13 years.
PROJECTED ACCRUAL: A total of 60 patients (10 per treatment arm) will be accrued for this
study within 10 months.
Allocation: Randomized, Primary Purpose: Treatment
Change in immune response as assessed by T-cells monthly
John L. Marshall, MD
Lombardi Cancer Research Center
United States: Food and Drug Administration
|Lombardi Comprehensive Cancer Center at Georgetown University Medical Center||Washington, District of Columbia 20007|