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

Mayo Clinic

Status and phase

Enrolling

Early Phase 1

Conditions

Glioma

Treatments

Drug: Dasatinib

Drug: Temozolomide

Drug: Quercetin

Drug: Fluorodopa F 18

Procedure: Magnetic Resonance Imaging

Procedure: Biospecimen Collection

Procedure: Positron Emission Tomography

Other: Patient Observation

Drug: Fisetin

Study type

Interventional

Funder types

Other

Identifiers

NCT07025226

NCI-2025-03841 (Registry Identifier)

MC230715 (Other Identifier)

23-008241 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment

10 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

10 participants in 6 patient groups

Regimen 1 (rest, no treatment)

Active Comparator group

Description:

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.

Treatment:

Other: Patient Observation

Procedure: Positron Emission Tomography

Procedure: Biospecimen Collection

Procedure: Magnetic Resonance Imaging

Drug: Fluorodopa F 18

Regimen 2 (dasatinib, quercetin)

Experimental group

Description:

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.

Treatment:

Procedure: Positron Emission Tomography

Procedure: Biospecimen Collection

Procedure: Magnetic Resonance Imaging

Drug: Quercetin

Drug: Fluorodopa F 18

Drug: Dasatinib

Regimen 3 (fisetin)

Experimental group

Description:

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.

Treatment:

Drug: Fisetin

Procedure: Positron Emission Tomography

Procedure: Biospecimen Collection

Procedure: Magnetic Resonance Imaging

Drug: Fluorodopa F 18

Regimen 4 (temozolomide)

Experimental group

Description:

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.

Treatment:

Procedure: Positron Emission Tomography

Procedure: Biospecimen Collection

Procedure: Magnetic Resonance Imaging

Drug: Fluorodopa F 18

Drug: Temozolomide

Regimen 5 (dasatinib, quercetin, temozolomide)

Experimental group

Description:

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.

Treatment:

Procedure: Positron Emission Tomography

Procedure: Biospecimen Collection

Procedure: Magnetic Resonance Imaging

Drug: Quercetin

Drug: Fluorodopa F 18

Drug: Temozolomide

Drug: Dasatinib

Regimen 6 (fisetin, temozolomide)

Experimental group

Description:

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.

Treatment:

Drug: Fisetin

Procedure: Positron Emission Tomography

Procedure: Biospecimen Collection

Procedure: Magnetic Resonance Imaging

Drug: Fluorodopa F 18

Drug: Temozolomide