RATIONALE: 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.
PURPOSE: Phase I trial to study the effectiveness of vaccine therapy with or without
sargramostim in treating patients who have advanced or metastatic cancer.
- 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.
- Determine the CEA-specific T-cell precursor frequency in patients treated with these
- Assess the immunogenicity of GM-CSF in patients treated with these regimens.
- Determine the inflammatory response and cytokine expression at the vaccination site in
- Correlate telomere length of leukocytes with prior cytotoxic therapies and immunologic
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.
PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study within 1. 2 years.
DISEASE CHARACTERISTICS:
- Histologically confirmed adenocarcinoma that failed standard curative options and for
which no standard palliative options are required within the next 8 weeks
- Advanced or metastatic disease
- Recurrent or unresectable disease
- Microscopic metastatic disease confirmed by surgical exploration allowed
- CEA expression by immunohistochemistry OR
- Circulating CEA greater than 5 ng/mL
- HLA phenotyping required
- HLA phenotyping must be repeated for patients who have undergone allogeneic bone
marrow transplantation
- No clinically symptomatic brain metastases
- Patients with brain metastases who have completed palliative radiotherapy and
have discontinued steroids are eligible
- Hormone receptor status:
- Not specified
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Sex:
- Male or female
Menopausal status:
- Not specified
Performance status:
- ECOG 0-1
Life expectancy:
- Not specified
Hematopoietic:
- WBC at least 3,000/mm^3
- Platelet count at least 100,000/mm^3
Hepatic:
- 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)
Renal:
- Creatinine less than 1. 5 mg/dL OR
- Creatinine clearance greater than 60 mL/min
- Proteinuria or hematuria less than +2 on urinalysis* OR
- Urine protein less than 1,000 mg/24-hour collection, if proteinuria greater than +1
NOTE: Proteinuria of +2 allowed provided etiology is non-renal
Gastrointestinal:
- 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
Neurologic:
- No uncontrolled seizure disorders
- No encephalitis
- No multiple sclerosis
Immunologic:
- No allergy to eggs
- No HIV-associated opportunistic infection
- No autoimmune diseases, including the following:
- Systemic lupus erythematosus
- Sjögren's syndrome
- Scleroderma
- Myasthenia gravis
- Goodpasture syndrome
- Addison's disease
- Hashimoto's thyroiditis
- Graves' disease
- Antinuclear antibody positive status allowed if no evidence of an autoimmune disease
Other:
- No direct contact of vaccination site with the following persons for at least 72 hours
after each vaccination:
- Children under 1 year of age
- Pregnant women
- Individuals with eczema or other open skin condition
- Immunocompromised individuals
- 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
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- 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
Chemotherapy:
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and
recovered
- No concurrent antineoplastic chemotherapy
Endocrine therapy:
- 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
Radiotherapy:
- See Disease Characteristics
- At least 4 weeks since prior radiotherapy and recovered
- No prior radiotherapy to more than 50% of all nodal groups
Surgery:
- See Disease Characteristics
- Recovered from prior surgery
- No prior splenectomy
Other:
- Concurrent non-steroidal anti-inflammatory drugs allowed
- No other concurrent anti-cancer therapy
