This early phase I trial tests the safety, side effects and how well medication combinations of dasatinib, quercetin, fisetin and temozolomide work in treating patients with glioma for which the patient has received treatment in the past (previously treated) and for tumor cells that remain after attempts to treat the tumor have been made (residual disease). Dasatinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply, which may help keep tumor cells from growing. Quercetin and fisetin are compounds found in plants. They have antioxidant and anti-inflammatory properties and help remove senescent cells, older or damaged cells that have stopped dividing but don't die off as they should and build up in tissues over time. Senescent cells may cause inflammation or damage to nearby healthy cells. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill tumor cells and slow down or stop tumor growth. Giving medication combinations of dasatinib, quercetin, fisetin and temozolomide may be safe, tolerable and/or effective in treating patients with previously treated glioma with residual disease.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Undergo blood and CSF sample collection
Given PO
Given PO
Undergo 18F-DOPA-PET scan
Undergo MRI
Receive rest and take no treatment
Undergo 18F-DOPA-PET scan
Given PO
Given PO
Mayo Clinic in Rochester
Rochester, Minnesota, United States
RECRUITINGCompletion of 3 cycles
Will evaluate feasibility of serially screening multiple candidate therapies or combinations based on individualized empiric biological feedback from biospecimens and imaging. This will be measured as the percentage of patients successfully completing 3 cycles of drug administration (study visits). A cycle is 35 +/- 7 days. Regimen will be considered feasible if at least 2/3 of patients can achieve this target.
Time frame: Up to 16 weeks
Turnaround time for scan and marker data
Will also evaluate feasibility as the turnaround time for scan and marker data that is used to determine if patients should stay on current therapy or move to the next regimen. The outcomes will be cycle-specific. A cycle is 35 +/- 7 days. The target for this is a mean turnaround time of 3 days; if the maximum turnaround time exceeds 5 days, this will prompt an evaluation of process to identify barriers.
Time frame: Up to 16 weeks (completion of 3 cycles)
Incidence of adverse events
Will assess the safety of this algorithm-based approach to individualized therapeutic drug combinations in patients with pre-recurrent central nervous system tumors. The study drugs will be considered well-tolerated with no grade 3 or higher adverse event attributable to the drugs in the 10 patients. Adverse events will be evaluated per the Common Terminology Criteria for Adverse Events (CTCAE) version 5 criteria and summarized by type and severity as well as perceived attribution to study treatment for each of the regimens received by patients.
Time frame: Up to 3 years
Change in senescence-associated proteins
Will evaluate relative change from baseline in enrichment for a panel of senescence-associated proteins in cerebrospinal fluid (CSF) for each sequentially administered senolytic agent. An effective senolytics regimen will decrease CSF senescence associated secretory phenotype, including monocyte chemoattractant protein-1 levels, by at least 25%.
Time frame: Baseline; up to 3 years
Cell-free mitochondrial deoxyribonucleic acid (DNA)
Will evaluate the percentage change in cell-free mitochondrial DNA. An effective senolytics regimen will decrease cell-free mitochondrial DNA by at least 25%.
Time frame: Baseline; up to 3 years
2-Hydroxyglutarate (2-HG)
Will evaluate the percentage change in 2-HG.
Time frame: Baseline; up to 3 years
Amplified DNA junctions
Will evaluate the percentage change in amplified DNA junctions (if applicable).
Time frame: Baseline; up to 3 years
Volume of disease
Will evaluate the percentage change in the volume of disease above a tumor to normal standardized uptake value maximum ratio of 2 from fluorodopa F 18-positron emission tomography.
Time frame: Baseline; up to 3 years
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