OBJECTIVES:

• 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 regimens.
• Assess the immunogenicity of GM-CSF in patients treated with these regimens.
• Determine the inflammatory response and cytokine expression at the vaccination site in these patients 48 hours after vaccination.
• 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.

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