INCLUSION CRITERIA:
A. Histologically confirmed adencarcinoma that is CEA or MUC-1 positive. Tumor that has been shown to express CEA or MUC-1 (greater than or equal to 20 % of cells) by immunohistochemical techniques or patients that have had an elevated serum CEA (greater than 5 microgram/L) at any point during their disease course.
B. Patients must have completed at least one 5-FU containing chemotherapy regimen (e.g. 5-FU/LV with or without either irinotecan or oxaliplatin) for the colorectal cancer arm, or either failed or not be a candidate for therapy of proven efficacy for their disease in the non-colorectal cancer arm.
C. 18 years of age or greater.
D. All patients on the colorectal adenocarcinoma cohort must be HLA-A2 positive.
E. At least 10 patients on the non-colorectal adenocarcinoma cohort must be HLA-A2 positive.
F. Metastatic disease (measurable or non-measurable) with a life expectancy of at least 4 months.
G. Able to understand and give informed consent.
H. Able to avoid close household contact (close household contacts are those who share housing or have close physical contact) for at least three weeks after recombinant vaccinia vaccination with persons with active or a history of eczema or other eczematoid skin disorders; those with other acute, chronic or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds) until condition resolves; pregnant or nursing women; children 5 years of age and under; and immunodeficient or immunosuppressed persons (by disease or therapy), including HIV infection.
I. ECOG performance status of 0 - 1.
J. Serum creatinine within the institution limits of normal, and AST less than or equal to twice the upper limits of normal (at National Naval Medical Center this is a serum creatinine less than or equal to 1.5 mg/dL OR creatinine clearance on a 24 hour urine collection of greater than or equal to 60 mL/min, a total bilirubin less than or equal to 1.3, and AST less than or equal to 98 U/L and mg/DL).
K. Total bilirubin within the institution limits of normal OR patients with Gilbert's syndrome, a total bilirubin less than or equal to 3.0
L. Recovered completely from any reversible toxicity associated with recent therapy. Typically this is 3-4 weeks for patients who most recently received cytotoxic therapy except for the nitrosoureas and mitomycin C for which 6 weeks is needed for recovery.
M. Hematological eligibility parameters (within 16 days of starting therapy):
- Granulocyte count greater than or equal to 1,500/mm3
- Platelet count greater than or equal to 100,000/mm3
- Lymphocyte count greater than or equal to 500/mm3
- Hgb equal to 10 Gm/dL
N. Prior immune therapy with related vaccinia and fowlpox vaccines or antigen-specific peptides is allowed.
O. Men and women must agree to use effective birth control or abstinence during and for a period of 4 months after the last vaccination therapy.
P. Patients with prostate cancer must continue to receive GnRH agonist therapy (unless orchiectomy has been done).
INCLUSION CRITERIA FOR EXTENSION PHASE:
A. Completion of Core phase of the protocol.
B. Stable or responding disease (PR, CR).
C. No dose limiting toxicity (see below) in Core phase possibly, probably or definitely related to the vaccine.
Dose limiting toxicities include:
- Any Grade 2 generalized urticaria or Grade 3 or greater allergic reaction.
- Any Grade 2 or greater autoimmune response.
- Any Grade 3 or greater hematologic or non-hematologic reaction, including injection-site reaction.
EXCLUSION CRITERIA:
A. Patients should have no evidence of being immunocompromised as listed below.
- Human immunodeficiency virus positivity due to the potential for decreased tolerance and risk for severe side effects
- Active autoimmune diseases requiring treatment or a history of autoimmune disease that might be stimulated by vaccine treatment. This requirement is due to the potential risks of exacerbating autoimmunity. Patients with endocrine disease that is controlled by replacement therapy including thyroid disease and adrenal disease and vitiligo may be enrolled.
- Concurrent use of systemic steroids, except for physiologic doses for systemic steroid replacement or local (topical, nasal, or inhaled) steroid use.
B. History of allergy or untoward reaction to prior vaccination with vaccinia virus
C. Pregnant or breast-feeding women
D. Altered immune function, including immunodeficiency or history of immunodeficiency; eczema; history of eczema, or other eczematoid skin disorders; or those with acute, chronic or exfoliative skin conditions (e.g. atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds)
E. Serious intercurrent medical illness which would interfere with the ability of the patient to carry out the treatment program, including, but not limited to, inflammatory bowel disease, Crohn's disease, ulcerative colitis, or active diverticulitis
F. Evidence of clinically active brain metastasis within two months of registration. History of seizures, encephalitis, or multiple sclerosis
G. Medical conditions, which, in the opinion of the investigators would jeopardize the patient or the integrity of the data obtained
H. Chemotherapy, radiation therapy, or any other anti-neoplastic therapy at the time of registration. Subjects who initiate any of these therapies during the trial will receive no further inoculations and will be removed from the study.
I. Serious hypersensitivity reaction to egg products
J. Clinically significant cardiomyopathy
K. Chronic hepatitis infection, including B and C, because of potential immune impairment
L. Although topical steroids are allowed, steroid eye drops are not permitted for two weeks prior and 4 weeks following the initial vaccine with a vaccinia vector. Persons with inflammatory eye conditions who may develop a requirement for eye drops during that time period are not eligible for study
M. Active infection with fever greater than 100 degrees F or requirement for antibiotics within 72 hours of enrollment.
Warren Grant Magnuson Clinical Center (CC)