Medication Combinations of Dasatinib, Quercetin, Fisetin, Temozolomide, LMP744, and Autologous TLPO Vaccine for the Treatment of Previously Treated Glioma With Residual Disease

NCT07025226 | Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: MC23071523-008241
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Glioma

Outcome Measures

Primary Outcomes (2)

• Completion 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.

  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.

  Up to 16 weeks (completion of 3 cycles)

Secondary Outcomes (6)

• Incidence of adverse events

  Up to 3 years

• Change in senescence-associated proteins

  Baseline; up to 3 years

• Cell-free mitochondrial deoxyribonucleic acid (DNA)

  Baseline; up to 3 years

• 2-Hydroxyglutarate (2-HG)

  Baseline; up to 3 years

• Amplified DNA junctions

  Baseline; up to 3 years

Study Arms (9)

Regimen 1 (1 cycle rest, assignment to treatment regimen)

ACTIVE COMPARATOR

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. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.

Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Imaging; Other: Patient Observation; Procedure: Positron Emission Tomography

Regimen 2 (dasatinib, quercetin)

EXPERIMENTAL

Patients receive dasatinib PO 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 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. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.

Procedure: Biospecimen Collection; Drug: Dasatinib; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Drug: Quercetin

Regimen 3 (fisetin)

EXPERIMENTAL

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. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.

Procedure: Biospecimen Collection; Drug: Fisetin; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography

Regimen 4 (temozolomide)

EXPERIMENTAL

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. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.

Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Drug: Temozolomide

Regimen 5 (dasatinib, quercetin, temozolomide)

EXPERIMENTAL

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. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.

Procedure: Biospecimen Collection; Drug: Dasatinib; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Drug: Quercetin; Drug: Temozolomide

Regimen 6 (fisetin, temozolomide)

EXPERIMENTAL

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. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.

Procedure: Biospecimen Collection; Drug: Fisetin; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Drug: Temozolomide

Monitoring Arm

EXPERIMENTAL

Patients take no treatment and undergo monitoring only. Patients receive rest as in Regimen 1 and do not proceed to any treatment on study. Patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo amino acid PET scans on study.

Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Imaging; Other: Patient Observation; Procedure: Positron Emission Tomography

Regimen 7 (LMP744)

EXPERIMENTAL

Patients receive LMP744 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. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.

Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Drug: Topoisomerase-1 Inhibitor LMP744

Regimen 8 (autologous TLPO vaccine)

EXPERIMENTAL

Patients receive autologous TLPO vaccine 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 MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study.

Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Drug: Single Agent Therapy

Interventions

Dasatinib DRUG

Given PO

Also known as: BMS 354825, BMS-354825, BMS354825, Dasatinib Hydrate, Dasatinib Monohydrate, Sprycel

Regimen 2 (dasatinib, quercetin); Regimen 5 (dasatinib, quercetin, temozolomide)

Fisetin DRUG

Given PO

Also known as: 3,3',4',7-Tetrahydroxyflavone, 7,3',4'-Flavon-3-ol

Regimen 3 (fisetin); Regimen 6 (fisetin, temozolomide)

Quercetin DRUG

Given PO

Also known as: 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-1-benzopyran-4-one, 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-chromen-4-one, C.I. Natural Yellow 10

Regimen 2 (dasatinib, quercetin); Regimen 5 (dasatinib, quercetin, temozolomide)

Patient Observation OTHER

Receive rest and take no treatment

Also known as: Active Surveillance, deferred therapy, expectant management, Observation, Watchful Waiting

Monitoring Arm; Regimen 1 (1 cycle rest, assignment to treatment regimen)

Positron Emission Tomography PROCEDURE

Undergo amino acid PET scan (optional)

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Monitoring Arm; Regimen 1 (1 cycle rest, assignment to treatment regimen); Regimen 2 (dasatinib, quercetin); Regimen 3 (fisetin); Regimen 4 (temozolomide); Regimen 5 (dasatinib, quercetin, temozolomide); Regimen 6 (fisetin, temozolomide); Regimen 7 (LMP744); Regimen 8 (autologous TLPO vaccine)

Temozolomide DRUG

Given PO

Also known as: CCRG-81045, Gliotem, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temizole, Temodal, Temodar, Temomedac, TMZ

Regimen 4 (temozolomide); Regimen 5 (dasatinib, quercetin, temozolomide); Regimen 6 (fisetin, temozolomide)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection, Sample Collection

Monitoring Arm; Regimen 1 (1 cycle rest, assignment to treatment regimen); Regimen 2 (dasatinib, quercetin); Regimen 3 (fisetin); Regimen 4 (temozolomide); Regimen 5 (dasatinib, quercetin, temozolomide); Regimen 6 (fisetin, temozolomide); Regimen 7 (LMP744); Regimen 8 (autologous TLPO vaccine)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Monitoring Arm; Regimen 1 (1 cycle rest, assignment to treatment regimen); Regimen 2 (dasatinib, quercetin); Regimen 3 (fisetin); Regimen 4 (temozolomide); Regimen 5 (dasatinib, quercetin, temozolomide); Regimen 6 (fisetin, temozolomide); Regimen 7 (LMP744); Regimen 8 (autologous TLPO vaccine)

Topoisomerase-1 Inhibitor LMP744 DRUG

Given IV

Also known as: 308246-52-8, Indenoisoquinoline, LMP744, LMP-744, 5H-(1,3)Dioxolo(5,6)indeno(1,2-C)isoquinoline-5,12(6H)-dione, 6-(3-((2-Hydroxyethyl)amino)propyl)-2,3-dimethoxy-

Regimen 7 (LMP744)

Single Agent Therapy DRUG

Given autologous TLPO vaccine ID

Also known as: Drug Monotherapy, Monotherapy, Single Agent Treatment, Single Drug Therapy

Regimen 8 (autologous TLPO vaccine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Prior diagnosis of a glioma treated with chemotherapy and/or radiation with stable disease based on Response Assessment in Neuro-Oncology (RANO) criteria
• Must have IDH-mutant OR MGMT-methylated glioma
• NOTE: Patients with any radiographic evidence of residual disease are eligible
• Eastern Cooperative Oncology Group (ECOG) of 0, 1, or 2, and Karnofsky performance status \>= 50
• Hemoglobin ≥ 9.0 g/dL (≤ 15 days prior to registration)
• Absolute neutrophil count (ANC) ≥ 1500/mm\^3 (≤ 15 days prior to registration)
• Platelet count ≥ 100,000/mm\^3 (without transfusion ≤ 7 days preceding lab assessment) (≤ 15 days prior to registration)
• Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 2.5 x upper limit of normal (ULN) (or ≤ 5 x ULN for patients with liver involvement) (≤ 15 days prior to registration)
• Calculated creatinine clearance ≥ 45 ml/min using the Cockcroft-Gault formula (≤ 15 days prior to registration)
• Average corrected QT interval (QTc) ≤ 450 ms on triplicate 12 lead electrocardiogram (ECG) ≤ 29 days prior to registration
• NOTE: QTc intervals will be corrected using Fridericia's formula (Fridericia 1920)
• Negative serum pregnancy test is required for persons of childbearing potential ≤ 8 days prior to registration
• Presence of an implanted cranial CSF access device, such as Ommaya reservoir or ventriculoperitoneal shunt
• Willingness to provide blood and CSF samples for research

You may not qualify if:

• Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:
• Pregnant persons
• Nursing persons
• Persons of childbearing potential and persons able to father a child who are unwilling to employ adequate contraception
• Patients who are not appropriate medical candidates due to current or past medical history or uncontrolled concurrent illness which limits safety of or compliance to study proceedings
• Participants who are unable to swallow tablets or who are at risk for impaired absorption of oral medication
• NOTE: This includes but not limited to, refractory vomiting, gastric resection/bypass, or duodenal/jejunal resection
• NOTE: An exception can be granted for such patients if no oral medications are planned (i.e., patient will receive only IV or intradermal agents)
• Patients with known hypersensitivity or allergy to all of the study drugs on the protocol (known hypersensitivity or allergy to one drug does not preclude participation in this protocol)
• Inability to undergo MRI scans
• NOTE: These patients may be enrolled in the Monitoring Arm
• Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:
• Pregnant persons
• Nursing persons
• Persons of childbearing potential and persons able to father a child who are unwilling to employ adequate contraception

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Related Links

• Mayo Clinic Clinical Trials
• Review article discussing the rationale for and general design of this study

MeSH Terms

Conditions

Glioma

Interventions

Specimen Handling; Dasatinib; fisetin; Magnetic Resonance Spectroscopy; Watchful Waiting; Observation; Quercetin; Temozolomide; Drug Therapy

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Spectrum Analysis; Chemistry Techniques, Analytical; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration; Methods; Flavonols; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Dacarbazine; Triazenes; Imidazoles; Therapeutics

Study Officials

• Terence C. Burns, MD, PhD

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trials Referral Office

CONTACT

855-776-0015; mayocliniccancerstudies@mayo.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2025
• First Posted: June 17, 2025
• Study Start: August 12, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: July 2, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)