Open Label Study to Evaluate the Safety and Tolerability of GI-6301 (Whole Heat-Killed Recombinant Yeast Modified to Express Brachyury Protein) in Adults With Solid Tumors
This is an open label, phase I trial with sequential dose escalation cohorts of patients (3-6 patients per dose cohort) for 4 doses of GI-6301 (Yeast-Brachyury vaccine).
GI-6301 (Yeast-Brachyury vaccine) will be administered subcutaneously at 4 sites biweekly for 7 visits (day 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 28 days on-study without dose limiting toxicities (DLT) before enrollment can begin on the next dose level or on the expansion phase.
Expansion Phase: 10 additional patients will be enrolled in the third dose group, receiving the same treatment regimen, to assess for immunologic responses and clinical responses. An additional 10 patients will be enrolled in the fourth dose group. Up to 38 patients may be theoretically required to complete this trial.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open Label Phase 1 Study to Evaluate the Safety and Tolerability of GI-6301 a Vaccine Consisting of Whole Heat-Killed Recombinant Saccharomyces Cerevisiae Yeast Genetically Modified to Express Brachyury Protein in Adults With Solid Tumors|
- Adverse events of escalating doses of GI-6301 vaccine [ Time Frame: At end of treatment (36 months) ] [ Designated as safety issue: Yes ]Type and Grade of treatment emergent adverse events.
- Change in T cell precursors [ Time Frame: 1 year ] [ Designated as safety issue: No ]Determine in an expanded cohort if a significant change in T cell precursors will be detectable as measured by an increase in Brachyury-specific T cell ELISPOT assay and proliferation.
- Clinical Benefit [ Time Frame: At the end of treatment (36 months) ] [ Designated as safety issue: No ]To evaluate evidence of clinical benefit, such as progression-free survival, clinical radiographic response, reduction in serum markers, and/or reduction in circulating tumor cells.
- General immune activation [ Time Frame: At the end of treatment (36 months) ] [ Designated as safety issue: No ]To evaluate parameters of general immune activation: Frequency of immune cell subsets in peripheral blood and changes in serum levels of cytokines.
|Study Start Date:||January 2012|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||June 2016 (Final data collection date for primary outcome measure)|
Experimental: GI-6301 Vaccine Arm
Escalating dose groups of 3-6 subjects to receive 4YU and 16YU; 13 subjects to receive 40YU and 10 subjects to receive 80YU.
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 to produce the final recombinant vaccine product.
This is an open label, phase I trial with sequential cohorts of patients (3-6 patients per dose cohort) with dose escalation of a heat-killed Yeast-Brachyury vaccine. Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits (Days 1, 15, 29, 43, 57, 71, 85 all +/- 2 days), then monthly until patients meet off-treatment criteria. The first 3 treatment cycles will consist of 2 vaccines and will last 28 days each; subsequent cycles will consist of one monthly vaccine treatment. Restaging of disease will be performed after the initial 3 cycles and then every 2 cycles thereafter.
For the first three patients on each dose level, there will be staggered enrollment of at least 2 weeks between patients.
Dose levels and responses to a vaccine are very different to drugs so we have no way of knowing a priori if a lower dose will result in more of a therapeutic anti-tumor immune response than a higher dose. Thus, up to 6 patients may be enrolled on each dose level in order to gain further information about safety and immunogenicity, providing that the maximally tolerated dose has not been exceeded.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01519817
|United States, Maryland|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||James L Gulley, M.D. Ph.D.||LTIB, CCR, NCI|