Clinical trial NCT07025226: Sequential Treatments or Combinations Including Dasatinib, Quercetin, Fisetin and/or Temozolomide for the Treatment of Previously Treated Glioma With Residual Disease
Official title: Pilot Study of the Mechanistic Feedback From CNS Tumors With Latent Residual Disease to Guide Individualized Therapies
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Glioma
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2025-06-17
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Completion of 3 cycles
timeFrame: Up to 16 weeks
measure: Turnaround time for scan and marker data
timeFrame: Up to 16 weeks (completion of 3 cycles)
Secondary outcomes:
measure: Incidence of adverse events
timeFrame: Up to 3 years
measure: Change in senescence-associated proteins
timeFrame: Baseline; up to 3 years
measure: Cell-free mitochondrial deoxyribonucleic acid (DNA)
timeFrame: Baseline; up to 3 years
measure: 2-Hydroxyglutarate (2-HG)
timeFrame: Baseline; up to 3 years
measure: Amplified DNA junctions
timeFrame: Baseline; up to 3 years
measure: Volume of disease
timeFrame: Baseline; up to 3 years
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic in Rochester
name: Terence C. Burns, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: