Sequential Treatments or Combinations Including Dasatinib, Quercetin, Fisetin and/or Temozolomide for the Treatment of Previously Treated Glioma With Residual Disease

Early Phase 1

Not yet recruiting

• Conditions: Glioma
• Interventions: Procedure: Biospecimen Collection; Drug: Fluorodopa F 18; Drug: Dasatinib; Drug: Fisetin; Procedure: Magnetic Resonance Imaging; Other: Patient Observation; Procedure: Positron Emission Tomography; Drug: Temozolomide; Drug: Quercetin

• Registration Number: NCT07025226
• Lead Sponsor: Mayo Clinic

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-09
• Study First Submitted QC: 2025-06-09
• Last Update Submitted: 2025-06-16
• Study First Posted: 2025-06-17
• Last Update Posted: 2025-06-18
• Study Start: 2025-07-01
• Primary Completion: 2027-09-01
• Study Completion: 2027-09-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

• 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

• Co-enrollment on the neuro-oncology biorepository [institutional review board (IRB) 12-003458] for collection of research blood and CSF samples

• Provide written informed consent

• Willingness to return to Mayo Clinic for follow-up

Exclusion Criteria

• 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

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Regimen 1 (rest, no treatment)	Biospecimen Collection	Patients receive rest and take no treatment on days 1-35 of cycle 1. Patients at the end of cycle 1 proceed to regimen 2. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 1 (rest, no treatment)	Fluorodopa F 18	Patients receive rest and take no treatment on days 1-35 of cycle 1. Patients at the end of cycle 1 proceed to regimen 2. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 2 (dasatinib, quercetin)	Biospecimen Collection	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 proceed to regimen 3. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 1 (rest, no treatment)	Magnetic Resonance Imaging	Patients receive rest and take no treatment on days 1-35 of cycle 1. Patients at the end of cycle 1 proceed to regimen 2. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 1 (rest, no treatment)	Patient Observation	Patients receive rest and take no treatment on days 1-35 of cycle 1. Patients at the end of cycle 1 proceed to regimen 2. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 1 (rest, no treatment)	Positron Emission Tomography	Patients receive rest and take no treatment on days 1-35 of cycle 1. Patients at the end of cycle 1 proceed to regimen 2. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 2 (dasatinib, quercetin)	Dasatinib	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 proceed to regimen 3. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 2 (dasatinib, quercetin)	Fluorodopa F 18	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 proceed to regimen 3. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 3 (fisetin)	Biospecimen Collection	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 proceed to regimen 4. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 3 (fisetin)	Fisetin	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 proceed to regimen 4. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 6 (fisetin, temozolomide)	Positron Emission Tomography	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 proceed to end of study treatment and study follow up. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 2 (dasatinib, quercetin)	Magnetic Resonance Imaging	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 proceed to regimen 3. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 2 (dasatinib, quercetin)	Positron Emission Tomography	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 proceed to regimen 3. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 2 (dasatinib, quercetin)	Quercetin	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 proceed to regimen 3. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 3 (fisetin)	Fluorodopa F 18	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 proceed to regimen 4. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 3 (fisetin)	Magnetic Resonance Imaging	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 proceed to regimen 4. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 3 (fisetin)	Positron Emission Tomography	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 proceed to regimen 4. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 4 (temozolomide)	Biospecimen Collection	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 proceed to regimen 5. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 4 (temozolomide)	Fluorodopa F 18	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 proceed to regimen 5. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 4 (temozolomide)	Magnetic Resonance Imaging	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 proceed to regimen 5. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 4 (temozolomide)	Positron Emission Tomography	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 proceed to regimen 5. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 4 (temozolomide)	Temozolomide	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 proceed to regimen 5. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 5 (dasatinib, quercetin, temozolomide)	Biospecimen Collection	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 proceed to regimen 6. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 5 (dasatinib, quercetin, temozolomide)	Dasatinib	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 proceed to regimen 6. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 5 (dasatinib, quercetin, temozolomide)	Fluorodopa F 18	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 proceed to regimen 6. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 5 (dasatinib, quercetin, temozolomide)	Magnetic Resonance Imaging	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 proceed to regimen 6. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 5 (dasatinib, quercetin, temozolomide)	Positron Emission Tomography	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 proceed to regimen 6. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 5 (dasatinib, quercetin, temozolomide)	Quercetin	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 proceed to regimen 6. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 5 (dasatinib, quercetin, temozolomide)	Temozolomide	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 proceed to regimen 6. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 6 (fisetin, temozolomide)	Biospecimen Collection	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 proceed to end of study treatment and study follow up. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 6 (fisetin, temozolomide)	Fisetin	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 proceed to end of study treatment and study follow up. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 6 (fisetin, temozolomide)	Fluorodopa F 18	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 proceed to end of study treatment and study follow up. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 6 (fisetin, temozolomide)	Magnetic Resonance Imaging	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 proceed to end of study treatment and study follow up. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.
Regimen 6 (fisetin, temozolomide)	Temozolomide	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 proceed to end of study treatment and study follow up. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo 18F-DOPA-PET scans on study.

Primary Outcome Measures

Name	Time	Method
Completion of 3 cycles	Up to 16 weeks	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.
Turnaround time for scan and marker data	Up to 16 weeks (completion of 3 cycles)	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.

Secondary Outcome Measures

Name	Time	Method
Incidence of adverse events	Up to 3 years	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.
Change in senescence-associated proteins	Baseline; up to 3 years	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%.
Cell-free mitochondrial deoxyribonucleic acid (DNA)	Baseline; up to 3 years	Will evaluate the percentage change in cell-free mitochondrial DNA. An effective senolytics regimen will decrease cell-free mitochondrial DNA by at least 25%.
2-Hydroxyglutarate (2-HG)	Baseline; up to 3 years	Will evaluate the percentage change in 2-HG.
Amplified DNA junctions	Baseline; up to 3 years	Will evaluate the percentage change in amplified DNA junctions (if applicable).
Volume of disease	Baseline; up to 3 years	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.

Trial Locations

Locations (1)

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States