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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

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 Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT07025226
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Early Phase 1
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Mayo Clinic
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Terence C. Burns, MD, PhD
Principal Investigator Affiliation	Mayo Clinic in Rochester
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries	United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Glioma
Study Website:	View Trial Website

Arms & Interventions

Arms

Active Comparator: Regimen 1 (rest, no treatment)

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.

Experimental: Regimen 2 (dasatinib, 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.

Experimental: Regimen 3 (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.

Experimental: Regimen 4 (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.

Experimental: Regimen 5 (dasatinib, quercetin, 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.

Experimental: Regimen 6 (fisetin, 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.

Interventions

Procedure: - Biospecimen Collection

Undergo blood and CSF sample collection

Drug: - Dasatinib

Given PO

Drug: - Fisetin

Given PO

Drug: - Fluorodopa F 18

Undergo 18F-DOPA-PET scan

Procedure: - Magnetic Resonance Imaging

Undergo MRI

Other: - Patient Observation

Receive rest and take no treatment

Procedure: - Positron Emission Tomography

Undergo 18F-DOPA-PET scan

Drug: - Quercetin

Given PO

Drug: - Temozolomide

Given PO

Contact a Trial Team

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Mayo Clinic in Rochester, Rochester, Minnesota

Status

Address

Mayo Clinic in Rochester

Rochester, Minnesota, 55905

Site Contact

Clinical Trials Referral Office

[email protected]

855-776-0015

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