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
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
Phase I trial to study the effectiveness of vaccine therapy with or without sargramostim in treating patients who have advanced or metastatic cancer. Vaccines may make the body build an immune response to kill tumor cells. Colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood. Combining vaccine therapy with sargramostim may make tumor cells more sensitive to the vaccine and may kill more tumor cells
PRIMARY OBJECTIVES:
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 CEA-expressing adenocarcinomas.
II. Determine the CEA-specific T-cell precursor frequency in patients treated with these regimens.
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.
Inclusion Criteria:
Histologically confirmed adenocarcinoma that failed standard curative options and for which no standard palliative options are required within the next 8weeks
CEA expression by immunohistochemistry
Circulating CEA greater than 5 ng/mL
HLA phenotyping required
No clinically symptomatic brain metastases
Hormone receptor status:
Male or female
Performance status - ECOG 0-1
WBC at least 3,000/mm^3
Platelet count at least 100,000/mm^3
Bilirubin less than 1.5 times upper limit of normal (ULN)
AST and ALT less than 3 times ULN
PT and PTT less than 1.5 times ULN (unless therapeutically anticoagulated)
Creatinine less than 1.5 mg/dL
Creatinine clearance greater than 60 mL/min
Proteinuria or hematuria less than +2 on urinalysis*
Urine protein less than 1,000 mg/24-hour collection, if proteinuria greater than +1
No frequent vomiting or severe anorexia
No more than 10% weight loss within the past 3 months
No inflammatory bowel disease, Crohn's disease, ulcerative colitis, or active diverticulitis
No uncontrolled seizure disorders
No encephalitis
No multiple sclerosis
No allergy to eggs
No HIV-associated opportunistic infection
No autoimmune diseases, including the following:
Antinuclear antibody positive status allowed if no evidence of an autoimmune disease
No direct contact of vaccination site with the following persons for at least 72 hours after each vaccination:
No other concurrent serious medical illness that would preclude study entry
No other malignancy within the past 2 years except excised basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception for at least 1 month before (female patients only), during, and for at least 3 months after study participation
See Disease Characteristics
No prior CEA-directed active immunotherapy
Prior CEA-directed antibody therapy allowed
At least 4 weeks since prior immunotherapy and recovered
No other concurrent antineoplastic biologic therapy or immunotherapy
At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
No concurrent antineoplastic chemotherapy
See Disease Characteristics
No concurrent antineoplastic hormonal therapy
No concurrent systemic steroids (inhaled steroids allowed)
Concurrent systemic mineralocorticoids (e.g., megestrol for appetite stimulation or fludrocortisone) allowed
Concurrent birth control pills allowed
See Disease Characteristics
At least 4 weeks since prior radiotherapy and recovered
No prior radiotherapy to more than 50% of all nodal groups
See Disease Characteristics
Recovered from prior surgery
No prior splenectomy
Concurrent non-steroidal anti-inflammatory drugs allowed
No other concurrent anti-cancer therapy