Open Label Phase I Study to Evaluate the Safety and Tolerability of Vaccine (GI-6207) Consisting of Whole, Heat-Killed Recombinant Saccharomyces Cerevisiae Genetically Modified to Express CEA Protein in Adults With Metastatic CEA-Expressing Carcinoma
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.
-To determine the safety and tolerability of escalating doses of a heat-killed yeast-based
vaccine that targets tumors that express CEA.
- 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
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
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
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
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
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the safety and tolerability of escalating doses of a heated-killed yeast-based vaccine that targets tumors that express CEA.
Ravi A Madan, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|