This early phase I trial tests the safety, side effects and how well medication combinations of dasatinib, quercetin, fisetin, temozolomide, LMP744, and autologous tumor lysate particle only (TLPO) vaccine 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. LMP744 works by interfering with a protein that tumor cells use to copy and repair their DNA. By blocking this repair process, the drug causes DNA damage so that tumor cells cannot survive. The autologous TLPO vaccine is made using material from a patient's own tumor. It delivers the tumor material to immune cells so they can learn to recognize and attack the cancer. Giving medication combinations of dasatinib, quercetin, fisetin, temozolomide, LMP744, and autologous TLPO vaccine may be safe, tolerable and/or effective in treating patients with previously treated glioma with residual disease.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07025226.
Locations matching your search criteria
United States
Minnesota
Rochester
Mayo Clinic in RochesterStatus: Active
Contact: Terence Calvin Burns
Phone: 507-284-2511
PRIMARY OBJECTIVE:
I. Determine the feasibility of transitioning patients with brain tumors from one candidate senolytic therapy to the next in a response-based adaptive approach.
SECONDARY OBJECTIVES:
I. Assess the safety of this algorithm-based approach to individualized therapeutic drug combinations in patients with pre-recurrent central nervous system (CNS) tumors.
II. Determine the feasibility of serially screening multiple candidate therapies or combinations based on individualized empiric biological feedback from biospecimens and imaging.
CORRELATIVE/TERTIARY OBJECTIVE:
I. Determine the interactions between cell-free mitochondrial DNA in cerebrospinal fluid (CSF) as well as candidate biomarkers of residual tumor including, CSF 2-hydroxyglutarate (as applicable), amplified chromosomal junctions (as applicable) in CSF and plasma, and -amino acid positron emission tomography (PET) scans, including during novel senolytic drug combinations.
OUTLINE: Patients are assigned to the Monitoring Arm or are assigned to initiate treatment in regimen 1.
MONITORING ARM: Patients receive rest as in Regimen 1 and do not proceed to any treatment on study.
REGIMEN 1: Patients receive rest and take no treatment on days 1-35 of cycle 1. At the end of cycle 1, patients may proceed to regimens 2, 3, 4, 5, 6, 7, or 8.
REGIMEN 2: Patients receive dasatinib orally (PO) once daily (QD) on days 1-2 and quercetin PO QD on days 1-2 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a partial response (PR) or complete response (CR) on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen.
REGIMEN 3: Patients receive fisetin PO QD on days 1-2 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen.
REGIMEN 4: Patients receive temozolomide PO QD on days 1-5 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen.
REGIMEN 5: Patients receive temozolomide PO QD on days 1-5, quercetin PO QD days 14-15 and dasatinib PO QD on days 14-15 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen.
REGIMEN 6: Patients receive temozolomide PO QD on days 1-5 and fisetin PO QD on days 14-15 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen.
REGIMEN 7: Patients receive topoisomerase-1 inhibitor LMP744 (LMP744) intravenously (IV) over 1 hour on days 1-5 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen.
REGIMEN 8: Patients receive autologous tumor lysate particle only cancer vaccine (autologous TLPO vaccine) intradermally (ID) on day 1 of cycles 1-3 and cycles 6, 9, and 12. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. NOTE: Patients may continue receiving autologous TLPO vaccine after proceeding to another regimen. Patients with a PR or CR may remain on the current regimen.
Additionally, patients undergo magnetic resonance imaging (MRI) throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.
After completion of study treatment, patients are followed up at 30 days.
Lead OrganizationMayo Clinic in Rochester
Principal InvestigatorTerence Calvin Burns
