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 ...

Background: Carcinoembryonic antigen (CEA) is overexpressed in multiple adenocarcinomas. Previous clinical studies utilizing CEA-based vaccine therapy have demonstrated safety, T-cell immune responses against CEA, and preliminary evidence of clinical benefit. Preclinical studies have shown that Saccharomyces-CEA (yeast-CEA) can induce a strong immune response to CEA as well as therapeutic antitumor responses in a CEA-transgenic host. Previous and ongoing clinical studies utilizing whole, heat-killed recombinant Saccharomyces cerevisiae yeast genetically modified to express mutated Ras (GI-4000) or hepatitis C (GI-5005) proteins demonstrated this vaccine vehicle to be well tolerated, with no product-related serious adverse events in \>200 treated subjects. Objectives: Primary -To determine the safety and tolerability of escalating doses of a heat-killed yeast-based vaccine that targets tumors that express CEA. Secondary * To evaluate CD4 and CD8 immunologic response as measured by an increase in CEA-specific T cells measured by ELISPOT in HLA-A2, -A3 and -A24(+) patients, and proliferation in response to CEA protein. * To evaluate evidence of clinical benefit, such as progression-free survival, RECIST criteria, reduction in serum markers, and/or reduction in circulating tumor cells. Eligibility: (dose escalation phase) Must have metastatic cancer that is CEA-positive (either a CEA serum level \> 5 ng/mL or a tumor that stains positive for CEA in \> 20% of a tumor block). Must have completed or had disease progression on at least one prior line of disease-appropriate therapy, or not be a candidate for therapy of proven efficacy for their disease. Must be ECOG Performance Status 0 2. Should have no autoimmune diseases; no evidence of immune dysfunction; no serious intercurrent medical illness; No untreated brain metastasis (or local treatment of brain metastases within the last 6 months) Any hypersensitivity reaction to yeast-based products. Eligibility: (extension phase: 10 additional patients at highest tested dose/MTD) Same as for the dose escalation phase with the following exceptions: * Patients must be HLA-A2, -A3, or -A24(+) for immunologic monitoring * ECOG PS = 0 1 Design: This is an open label, phase I trial with sequential cohorts of patients (3-6 patients per dose cohort) with dose escalation of heat-killed GI-6207 vaccine (see statistical analysis section). GI 6207 vaccine will be administered subcutaneously at 4 sites biweekly for 7 visits (days 1, 15, 29, 43, 57, 71, 85), then monthly until patients meet off-study criteria. All patients on a given dose level will have completed 1 month on-study before enrollment can begin on the next dose level or on the extension phase (see statistical analysis section).