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 ...

Breast Cancer Clinical Trial

Official title: 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

Status Completed

Clinical Trial Summary

Objectives:

• To find out the maximum tolerated dose of the GI-6207 vaccine (the highest dose that does not cause unacceptable side effects), and to evaluate any side effects.

• To see if GI-6207 has any effect on patients tumors.

• To learn how the vaccine causes immune responses against the cancer.

Eligibility:

• Patients 18 years of age and older who have been diagnosed with a cancer that has not responded to standard treatments. Patients must not be allergic to yeast or yeast products.

Design:

• Initial physical examination, blood and tissue sampling, computed tomography (CT) scan, and skin test to determine eligibility for the procedure.

• Treatment with GI-6027 in seven 14-day cycles as follows:

• Vaccine administered on days 1, 15, 29, 43, 57, 71, and 85.

• Vaccine given at four sites around the body: right and left chest area below the armpit, and right and left upper thigh in the pelvic region. (These areas drain into parts of your body that contain large numbers of lymph nodes. The lymph nodes contain immune cells that may be activated by the vaccine to target cancer cells.)

• Clinic visits for physical examinations to check vital signs, take additional blood and urine samples, and perform other tests needed for the study.

• After day 85 (about 3 months), patients will continue to receive vaccine monthly (or every 28 days) as long as the vaccine is not producing harmful effects or side effects and the cancer is either stable or reducing. Patients who do well on the vaccine may continue to receive it for as long as it is available.

Clinical Trial Description

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). ;

Related Conditions & MeSH terms

• Breast Cancer
• Colorectal Cancer
• Colorectal Neoplasms
• Head and Neck Cancer
• Head and Neck Neoplasms
• Lung Cancer
• Prostate Cancer

• NCT number: NCT00924092
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 1
• Start date: March 13, 2009
• Completion date: August 2, 2012