Vaccine Therapy, GM-CSF, and Interferon Alfa-2b in Treating Patients With Locally Advanced or Metastatic Cancer That Expresses Carcinoembryonic Antigen (CEA)

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose and recommended phase II dose of interferon alfa-2b
(IFN-α-2b) when administered with recombinant vaccinia-CEA(6D)-TRICOM vaccine, recombinant
fowlpox-CEA(6D)-TRICOM vaccine, and sargramostim (GM-CSF) in patients with locally advanced
or metastatic carcinoembryonic antigen (CEA)-expressing carcinoma.

SECONDARY OBJECTIVES:

I. Determine the effect of IFN-α-2b on tumor cell expression of CEA and MHC class I antigens
in patients treated with this regimen.

II. Determine the immunologic effects of this regimen in these patients. III. Determine any
objective anti-tumor responses that may occur in response to this regimen in these patients.

IV. Determine the time to tumor progression in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of interferon alfa-2b (IFN-α-2b).

COURSE I: Patients receive recombinant vaccinia-CEA(6D)-TRICOM vaccine subcutaneously (SC)
on day 1. Patients also receive sargramostim (GM-CSF) SC on days 1-4 and IFN-α-2b* SC on
days 9, 11, and 13.

COURSES II-IV: Patients receive recombinant fowlpox-CEA(6D)-TRICOM vaccine SC on day 1.
Patients also receive GM-CSF as in course 1 and IFN-α-2b* SC on days 1, 3, and 5.

NOTE: *The initial cohort of 6 patients does not receive IFN-α-2b.

Treatment repeats every 28 days for 4 courses in the absence of disease progression or
unacceptable toxicity. After 4 courses, patients who do not have progressive disease or
unacceptable toxicity may receive recombinant fowlpox-CEA (6D)-TRICOM vaccine, GM-CSF, and
IFN-α-2b every 28 days for 2 more courses and then every 3 months for up to 2 years.

Cohorts of 3-6 patients receive escalating doses of IFN-α-2b until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity. Six additional patients are treated at the
MTD; these patients must be HLA-A2 positive.

After completion of study treatment, patients are followed monthly for 4 months and then
every 6-12 months for up to 15 years.

Inclusion Criteria:

- Histologically confirmed carcinoembryonic antigen (CEA)-expressing carcinoma

- Metastatic or locally advanced disease

- Tumor accessible for biopsy

- Must have received ≥ 1 prior systemic regimen for metastatic disease

- No known brain metastases

- Performance status - ECOG 0-2

- Performance status - Karnofsky 60-100%

- More than 6 months

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Bilirubin ≤ 2.0 times upper limit of normal (ULN)

- AST and ALT ≤ 4.0 times ULN

- Hepatitis B negative

- Hepatitis C negative

- Creatinine ≤ 1.96 mg/dL

- Creatinine clearance > 50 mL/min

- No persistent proteinuria

- Protein < 1,000 mg by 24-hour urine collection

- No urinary sediment abnormalities

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

- No clinically significant cardiomyopathy requiring treatment

- No impaired function (i.e., ejection fraction < 50%) for patients who have not had
prior vaccine and are asymptomatic

- HIV negative

- No ongoing or active infection

- No history of allergic reaction to eggs or egg products

- No history of allergy or untoward reaction to prior vaccinia vaccination (e.g.,
smallpox immunization) or to any of its components

- No history of or active eczema or other eczematoid skin disorders

- No atopic dermatitis

- No other acute, chronic, or exfoliative skin conditions, including any of the
following:

- Burns

- Impetigo

- Varicella zoster

- Severe acne

- Other open wounds or rashes

- No immunocompromised condition

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for ≥ 3 months after
completion of study treatment

- No sexual contact for 3 weeks after each vaccination treatment

- Must be willing to undergo tumor biopsy

- No psychiatric illness or social situation that would preclude study compliance

- No life-threatening illness

- No other active malignancy within the past 2 years except nonmelanoma skin cancer or
superficial bladder or cervical lesions treated with surgical resection

- No other uncontrolled illness

- Must be able to avoid close household contact with the following individuals for ≥ 3
weeks after vaccinia vaccination:

- Pregnant or nursing women

- Children under 5 years of age

- Individuals who are immunodeficient or immunosuppressed by disease or therapy
(including HIV infection)

- Individuals with the following conditions:

- History of or active eczema or other eczematoid skin disorders

- Atopic dermatitis

- Other acute, chronic, or exfoliative skin conditions (e.g., burns,
impetigo, varicella zoster, severe acne, or other open rashes or wounds)

- No concurrent influenza vaccine

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
and recovered

- No concurrent steroid therapy, except topical or inhaled steroids

- No concurrent steroid eye drops

- More than 4 weeks since prior radiotherapy and recovered

- More than 4 weeks since prior surgery and recovered

- No prior splenectomy

- No other concurrent investigational agents