Cancer Vaccine Targeting Brachyury Protein in Tumors
- Cancer vaccines are being developed to help teach the body's immune system to attack and destroy cancer cells. A new vaccine being tested targets Brachyury protein. This protein is present in some tumor cells, and it can help tumor cells spread to other parts of the body. Researchers want to see whether the new Brachyury protein vaccine can help treat people with advanced carcinomas.
- To test the safety and effectiveness of a cancer vaccine that targets Brachyury protein in tumor cells.
- Individuals at least 18 years of age who have advanced cancers that have not responded or are no longer responding to standard treatments.
- Because the vaccine is made with yeast, people with yeast allergies will not be eligible.
- Participants will be screened with a medical history and physical exam. Imaging studies will be used to examine the cancer. Heart and thyroid function tests will be conducted. Blood and urine samples will also be collected.
- Participants will receive vaccine injections every 2 weeks, for a total of seven visits. After seven visits, if the cancer has shrunk or stopped growing, participants will continue to have the vaccine about once a month.
- Treatment will be monitored with frequent blood tests and imaging studies. Other tests will be given as directed by the study doctors. Some participants will have apheresis to collect additional blood cells for study.
- Participants will continue to receive the vaccine as long the tumor does not start growing again and there are no serious side effects....
|Neoplasms Malignant Solid Tumors Colon Neoplasms Adenocarcinoma||Biological: GI-6301 (Yeast Brachyury Vaccine)||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||An Open Label Phase I Study to Evaluate the Safety and Tolerability of GI-6301 Vaccine Consisting of Whole, Heat-Killed Recombinant Saccharomyces Cerevisiae (Yeast) Genetically Modified to Express Brachyury Protein in Adults With Solid Tumors|
- Number of Participants With Brachyury-Specific T-cell Responses [ Time Frame: Baseline (pre-vaccination) and approximately day 84 (after 6 vaccinations) ]A fluorescense activated cell sorting (FACS)-based assay for cluster of differentiation 4 (CD4) or cluster of differentiation 8 (CD8) T-cells expressing the cytokines interferon (IFN) gamma, interleukin 2 (IL2), and tumor necrosis factor (TNF) alpha, and/or cluster of differentiation 107a (CD107a) (a marker for lytic potential) was used to determine the numbers of participants showing development or enhancement of the level of brachyury-specific T-cells after vaccination.
- Count of Participants With Adverse Events of Escalating Doses of Yeast Brachyury ( GI- 6301) Vaccine [ Time Frame: 4 years and 25 days ]Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. A non-serious adverse event is any untoward medical occurrence.
- Number of Participants With a Clinical Benefit Assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: 3 and 5 months restaging ]Clinical benefit is defined as partial response (PR) or stable disease (SD) and was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Partial response is ≥30% decrease in the sum of greatest diameters/no new lesions. Progressive disease is ≥20% increase in the sum of greatest diameters/new lesions. Stable disease does not meet criteria for complete response (disappearance of all lesions; no new lesions), partial response, or progressive disease.
- Changes in Immune Cell Subsets in Peripheral Blood Mononuclear Cells (PBMC) [ Time Frame: Pre (Baseline) and Day 85 after 6 vaccinations ]Blood samples will be collected via apheresis and analyzed by multicolor flow cytometry in PBMCs for cluster of differentiation 4 (CD4), cluster of differentiation 8 (CD8), Natural Killer (NK), Natural Killer T (NKT), conventional dendritic cell (cDC), plasmacytoid dendritic cell (pDC), myeloid-derived suppressor cell (MDSC), Tregs, CD4 central memory (CD4 CM), CD4 effector memory (CD4 EM), CD4 terminal effector memory (CD4 EMRA), CD4 naïve, CD8 CM, CD8 EM, CD8 EMRA, and CD8 naïve cells. Significance of changes in immune cells was determined by p value (Wilcoxon test) and the median and interquartile range of data.
- Changes in Serum Levels of Cytokines [ Time Frame: Pre (Baseline) and Day 85 after 6 vaccinations ]Blood samples were collected and changes in serum levels of cytokines interferon gamma (IFNg), Interleukin 10 (IL-10), Interleukin 12 (IL-12)p70, Interleukin 1b (IL-1b), Interleukin 2 (IL-2), Interleukin 6 (IL-6), Interleukin 8 (IL-8), and tumor necrosis factor (TNF) were assessed by the multiplexed mesoscale assay. Significance of changes in serum levels of cytokines was determined by p value (Wilcoxon test) and the median and interquartile range of data.
- Changes in Soluble Cluster of Differentiation 27 (sCD27) [ Time Frame: Pre (Baseline) and Day 85 after 6 vaccinations ]Blood samples were collected and changes in serum levels of soluble sCD27 were assessed by enzyme-linked immunosorbent assay (ELISA). Significance of changes in soluble sCD27 was determined by p value (Wilcoxon test) and the median and interquartile range of data.
- Median Ratio of Soluble Cluster of Differentiation 27:40L (sCD27:sCD40L) [ Time Frame: Pre (Baseline) and Day 85 after 6 vaccinations ]Blood samples were collected and changes in serum levels of the ratio of soluble sCD27:sCD40L was assessed by enzyme-linked immunosorbent assay (ELISA). Significance of changes in soluble sCD27:sCD40L was determined by p value (Wilcoxon test) and the median and interquartile range of data.
- Changes in Soluble Cluster of Differentiation 40L (sCD40L) [ Time Frame: Pre (Baseline) and Day 85 after 6 vaccinations ]Blood samples were collected and changes in serum levels of soluble sCD27 were assessed by enzyme-linked immunosorbent assay (ELISA). Significance of changes in soluble sCD40L was determined by p value (Wilcoxon test) and the median and interquartile range of data.
|Actual Study Start Date:||January 5, 2012|
|Estimated Study Completion Date:||January 1, 2018|
|Primary Completion Date:||March 3, 2016 (Final data collection date for primary outcome measure)|
Experimental: Yeast-Brachyury vaccine
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Biological: GI-6301 (Yeast Brachyury Vaccine)
GI-6301 is a heat-killed, recombinant yeast-based vaccine engineered to express the transcription factor, Brachyury. The Brachyury gene is used to transfect the parental yeast strain (S. cerevisiae W303 - a haploid strain with known mutations from wildtype yeast) to produce the final recombinant vaccine product.
Other Name: Yeast-Brachyury vaccine
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01519817
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||James L Gulley, M.D.||National Cancer Institute (NCI)|