This phase I trial tests the safety, side effects, and best dose of triapine in combination with temozolomide in treating patients with glioblastoma that has come back after a period of improvement (recurrent). Triapine inhibits an enzyme responsible for producing molecules required for the production of deoxyribonucleic acid (DNA), which may inhibit tumor cell growth. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill tumor cells and slow down or stop tumor growth. Giving triapine in combination with temozolomide may be safe, tolerable, and/or effective in treating patients with recurrent glioblastoma.
Patients must have histologically confirmed World Health Organization (WHO) grade 2-4 glioma, isocitrate dehydrogenase (IDH) wild type (WT) (by immunohistochemistry [IHC] R132H negative [neg] or sequencing). Astrocytoma with molecular features of glioblastoma (GBM). Confirmed diagnosis via molecular testing
Group 1 and 2: recurrent glioblastoma
Group 3: Surgically amenable recurrent glioblastoma
Patients must have stable or decreasing dose of corticosteroids equivalent to ≤ 6 mg dexamethasone, for ≥ 7 days prior to registration
Patients who have a prior or concurrent malignancy that may interfere with study treatment or safety
NOTE: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible, per principal investigator (PI) discretion
Patients who are receiving any other investigational agents.
Exceptions: COVID-19 vaccine and treatment is allowed, per PI's discretion
Sequential
Biospecimen Collection
Procedure/SurgeryUndergo collection of blood samples
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Questionnaire Administration
Other interventionAncillary studies
Resection
Procedure/SurgeryUndergo surgical resection
Temozolomide
DrugGiven PO
Triapine
DrugGiven PO
Recommended phase 2 dose for triapine in combination with temozolomide
The recommended phase 2 dose will be based on treatment-emergent and drug-related toxicity. Dose limiting toxicities and adverse events (AEs) will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0.
Incidence of AEs and serious AEs
Will evaluate the occurrence of toxicity (AEs and serious AEs) and the number of patients who discontinue treatment due to toxicity. Toxicity will be assessed by CTCAE v. 5.0. Adverse events will be sorted (by type, severity \[grade\], timing, and attribution to triapine), collected, and reported according to CTCAE v5.0.
Progression free survival (PFS)
Progression will be determined by clinical progression or by radiographic imaging as assessed by Response Assessment in Neuro-Oncology (RANO) criteria. The median and corresponding 95% confidence interval will also be estimated.
Overall survival
Will be described by Kaplan-Meier curve. The median and corresponding 95% confidence interval will also be estimated.
Overall response rate (ORR)
ORR will be assessed by RANO criteria. To determine the ORR, this endpoint will calculate the proportion of treated patients who experience an overall response (complete response \[CR\] or partial response \[PR\] per RANO criteria). The date of first response for either CR or PR will be used for the calculation of ORR. Will be estimated using the expansion cohort, along with its 95% confidence interval.
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Northwestern University
Lead sponsor
National Cancer Institute (NCI)
Collaborator
Nanopharmaceutics
Collaborator
BrainUp
Collaborator
