Early Phase 1 Window of Opportunity Study of Oral DSP-0390 in Gliomas
Summary
This study focuses on determining the pharmacokinetic and pharmacodynamic effect of DSP-0390 in brain and blood from patients with IDH-mutant glioma undergoing tumor resection. Tissue will be collected during surgical resection. Blood will be drawn at various time points throughout the 2 weeks of treatment. The hypothesis is that DSP-0390 will accumulate in brain tumor tissue at pharmacologically relevant concentrations, and that alterations in cholesterol metabolism driven by mutant IDH will increase susceptibility to DSP-0390 and lead to tumor cell death.
Arms & interventions
- DrugDSP-0390
DSP-0390 will be administered orally with preferably 200 mL of water, or approximately one-half cup water. The patient will take DSP-0390 after a minimum of a 6-hour fast and will fast for 1 hour after taking the dose.
Outcome measures
Primary
Unbound DSP-0390 concentration in non-enhancing tumor tissue
Unbound DSP-0390 concentration in non-enhancing tumor tissue will be quantified using tissue removed during resection after treatment.
Time frame: At time of surgery following treatment (estimated to be 2 weeks)
Changes in DSP-0390 concentration in plasma
Unbound DSP-0390 concentration in plasma will be quantified using blood samples taken throughout treatment.
Time frame: From start of treatment through end of treatment (estimated to be 2 weeks)
Secondary
Incidence of treatment emergent adverse events (TEAEs)
Time frame: From start of treatment through 30 day follow-up (estimated to be 6 weeks)
Incidence of grade 3 or higher study drug related adverse events (AEs)
Time frame: From start of treatment through 30 day follow-up (estimated to be 6 weeks)
Lathosterol levels in non-enhancing tumor tissue
Time frame: At time of surgery following treatment (estimated to be 2 weeks)
Changes in lathosterol levels in non-enhancing tumor tissue
Time frame: Baseline and at time of surgery following treatment (estimated to be 2 weeks)
Zymostenol levels in non-enhancing tumor tissue
Time frame: At time of surgery following treatment (estimated to be 2 weeks)
Changes in zymostenol levels in non-enhancing tumor tissue
Time frame: Baseline and at time of surgery following treatment (estimated to be 2 weeks)
Lathosterol/zymostenol (L/Z) ratio in non-enhancing tumor tissue
Time frame: At time of surgery following treatment (estimated to be 2 weeks)
Changes in lathosterol/zymostenol (L/Z) ratio in non-enhancing tumor tissue
Time frame: Baseline and at time of surgery following treatment (estimated to be 2 weeks)
Changes in lathosterol levels in blood
Time frame: From start of treatment through 5 days of treatment
Changes in lathosterol levels in blood
Time frame: From start of treatment through 10 days of treatment
Changes in lathosterol levels in blood
Time frame: From start of treatment through 11 days of treatment
Changes in lathosterol levels in blood
Time frame: From start of treatment through day 15
Changes in lathosterol levels in blood
Time frame: From start of treatment through day 16
Changes in zymostenol levels in blood
Time frame: From start of treatment through 5 days of treatment
Changes in zymostenol levels in blood
Time frame: From start of treatment through 10 days of treatment
Changes in zymostenol levels in blood
Time frame: From start of treatment through 11 days of treatment
Changes in zymostenol levels in blood
Time frame: From start of treatment through day 15
Changes in zymostenol levels in blood
Time frame: From start of treatment through day 16
Changes in L/Z ratio in blood
Time frame: From start of treatment through 5 days of treatment
Changes in L/Z ratio in blood
Time frame: From start of treatment through 10 days of treatment
Changes in L/Z ratio in blood
Time frame: From start of treatment through 11 days of treatment
Changes in L/Z ratio in blood
Time frame: From start of treatment through day 15
Changes in L/Z ratio in blood
Time frame: From start of treatment through day 16
Eligibility criteria
Study locations (1)
Washington University School of Medicine
St Louis, Missouri, 63110