An Open Label Phase I Study to Eval the Safety and Tolerability of a Vaccine (GI-6207) Consisting of Whole, Heat-killed Recombinant Saccharomyces Cerevisiae (Yeast) Genetically Modified to Express CEA Protein in Adults With Metastatic CEA-expressing …

INCLUSION CRITERIA:

A. Histologically confirmed carcinoma by the NIH Laboratory of Pathology that has been shown to express CEA (either a CEA serum level > 5 microg/L or a tumor that stains positive for CEA in > 20% of a tumor block).

B. Completed or had disease progression on at least one prior line of disease-appropriate therapy for metastatic disease, or not be a candidate for therapy of proven efficacy for their disease.

C. 18 years of age or greater.

D. Must have metastatic disease that is measurable or non-measurable but evaluable (e.g., pleural effusion or present on bone scan).

E. Ability to understand and the willingness to sign a written informed consent document.

F. ECOG performance status of 0 2 (Karnofsky greater than or equal to 50).

G. Serum creatinine less than or equal to 1.5 times upper limit of normal OR creatinine clearance on a 24-h urine collection of greater than or equal to 60 mL/min.

H. ALT and AST less than or equal to 2.5 times the upper limits of normal.

I. Total bilirubin less than or equal to 1.5 times upper limit of normal OR in patients with Gilbert s syndrome, a total bilirubin less than or equal to 3.0.

J. 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. There should be a minimum of 2 weeks from any prior chemotherapy, immunotherapy and/or radiation.

K. Hematological eligibility parameters (within 16 days of starting therapy):

Granulocyte count greater than or equal to 1,500/mm(3)
Platelet count greater than or equal to 100,000/mm(3)

L. Prior immune therapy (e.g. related vaccinia and fowlpox vaccines or antigen-specific peptides) is allowed.

M. 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.

N. Patients with prostate cancer must continue to receive GnRH agonist therapy (unless orchiectomy has been done).

O. Patients must be negative for yeast allergy skin test.

P. Patients must have baseline pulse oximetry greater than 90% on room air.

INCLUSION CRITERIA (EXTENSION PHASE: 10 ADDITIONAL PATIENTS AT HIGHEST TESTED DOSE/MTD):

Eligibility: Same as with the dose escalation phase with the following exceptions:

Patients must be HLA-A2, A3, or A24 positive for immunologic monitoring.
ECOG PS equal to 0 1.

EXCLUSION CRITERIA:

A. Patients should have no evidence of immune dysfunction as listed below.

Human immunodeficiency virus positivity due to the potential for decreased immune response to the vaccine.
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 autoimmune disease that is controlled by replacement therapy, including thyroid disease and adrenal disease; or those with 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. Limited doses of systemic steroids to prevent IV contrast, allergic reaction, or anaphylaxis (in patients who have known contrast allergies) are allowed.

B. History of allergy or untoward reaction to yeast-based products (any hypersensitivity to yeast-based products will be excluded).

C. Pregnant or breast-feeding women.

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. Untreated brain metastases (or local treatment of brain metastases within the last 6 months) due to the poor prognosis of these patients and difficulty ascertaining the cause of neurologic toxicities.

G. Concurrent chemotherapy. An exception is to allow for patients on the extension phase only with breast cancer who are receiving trastuzumab to continue therapy with trastuzumab while receiving the vaccine treatment.

K. Chronic hepatitis infection, including B and C, because of potential immune impairment.

L. Patients requiring continuous tricyclic antidepressant therapy should be excluded due to the interference with the yeast skin test in creating false negative test results.