MC230715 Pilot Study of the Mechanistic Feedback From CNS Tumors With Latent Residual Disease to Guide Individualized Therapies
This early phase I trial tests the safety, side effects and how well medication combinations of dasatinib, quercetin, fisetin, temozolomide, LMP744, and autologous tumor lysate particle only (TLPO) vaccine 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. LMP744 works by interfering with a protein that tumor cells use to copy and repair their DNA. By blocking this repair process, the drug causes DNA damage so that tumor cells cannot survive. The autologous TLPO vaccine is made using material from a patient's own tumor. It delivers the tumor material to immune cells so they can learn to recognize and attack the cancer. Giving medication combinations of dasatinib, quercetin, fisetin, temozolomide, LMP744, and autologous TLPO vaccine may be safe, tolerable and/or effective in treating patients with previously treated glioma with residual disease.
• 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
• Age ≥ 18 years
• Prior diagnosis of a glioma
• Negative serum pregnancy test is required for persons of childbearing potential ≤ 8 days prior to registration
• 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