Sequenced or combined dasatinib, quercetin, fisetin, and temozolomide for adults with previously treated glioma and remaining tumor

MC230715 Pilot Study of the Mechanistic Feedback From CNS Tumors With Latent Residual Disease to Guide Individualized Therapies

This trial will try different sequences or combinations of dasatinib, the plant compounds quercetin and fisetin, and the chemotherapy temozolomide to see if they are safe and help adults with previously treated glioma that still has residual tumor.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Mayo Clinic (Academic / other)
• Drugs / interventions: chemotherapy, radiation, dasatinib
• Locations: 1 site (Rochester, Minnesota)
• Trial ID: NCT07025226 on ClinicalTrials.gov

What this trial studies

This is an early phase I, single-site trial testing safety, side effects, and initial activity of various sequences and combinations of dasatinib, quercetin, fisetin, and temozolomide in adults with previously treated glioma that has radiographic residual disease. Participants will receive planned drug regimens with imaging and biospecimen collection (including PET and MRI) to monitor response and collect pharmacologic and biological data. Eligible patients must have IDH-mutant or MGMT-methylated glioma, adequate organ function, and ECOG performance status 0–2. The primary focus is on safety and tolerability, with secondary observations about tumor control and biological effects of the combinations.

Who should consider this trial

Good fit: Adults (≥18) with previously treated glioma who have radiographic residual disease and tumors that are IDH-mutant or MGMT-methylated, with ECOG 0–2 and adequate blood counts and organ function are the intended candidates.

Not a fit: Patients whose tumors are not IDH-mutant or not MGMT-methylated, those with very poor performance status or inadequate organ function, or those unable to tolerate the study drugs are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, these combinations might better control remaining tumor cells and delay disease progression, potentially extending time without worsening of the tumor.

How similar studies have performed: Temozolomide is an established chemotherapy for glioma and dasatinib has shown limited activity in some brain-tumor settings, while using quercetin and fisetin as senolytic agents in cancer treatment is largely experimental, so this specific combination approach is novel.

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

Where this trial is running

Rochester, Minnesota

• Mayo Clinic in Rochester — Rochester, Minnesota, United States (Recruiting)

Study contacts

• Principal investigator: Terence C. Burns, MD, PhD — Mayo Clinic in Rochester
• Study coordinator: Clinical Trials Referral Office

Conditions Glioma