This study focuses on determining the pharmacokinetic and pharmacodynamic effect of DSP-0390 in brain and blood from patients with IDH-mutant WHO grade II or III 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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
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.
Washington University School of Medicine
St Louis, Missouri, United States
RECRUITINGUnbound 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)
Incidence of treatment emergent adverse events (TEAEs)
Assessed using CTCAE v5.0
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)
Assessed using CTCAE v5.0
Time frame: From start of treatment through 30 day follow-up (estimated to be 6 weeks)
Lathosterol levels in non-enhancing tumor tissue
Lathosterol levels 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 lathosterol levels in non-enhancing tumor tissue
Lathosterol levels in non-enhancing tumor tissue will be quantified using tissue removed during resection after treatment.
Time frame: Baseline and at time of surgery following treatment (estimated to be 2 weeks)
Zymostenol levels in non-enhancing tumor tissue
Zymostenol levels 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 zymostenol levels in non-enhancing tumor tissue
Zymostenol levels in non-enhancing tumor tissue will be quantified using tissue removed during resection after treatment.
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
L/Z ratio 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 lathosterol/zymostenol (L/Z) ratio in non-enhancing tumor tissue
L/Z ratio in non-enhancing tumor tissue will be quantified using tissue removed during resection after treatment.
Time frame: Baseline and at time of surgery following treatment (estimated to be 2 weeks)
Changes in lathosterol levels in blood
Change in lathosterol levels in blood will be quantified after 5 days of DSP-0390 dosing.
Time frame: From start of treatment through 5 days of treatment
Changes in lathosterol levels in blood
Change in lathosterol levels in blood will be quantified after 10 days of DSP-0390 dosing.
Time frame: From start of treatment through 10 days of treatment
Changes in lathosterol levels in blood
Change in lathosterol levels in blood will be quantified after 11 days of DSP-0390 dosing.
Time frame: From start of treatment through 11 days of treatment
Changes in lathosterol levels in blood
Change in lathosterol levels in blood will be quantified after 15 days of DSP-0390 dosing.
Time frame: From start of treatment through day 15
Changes in lathosterol levels in blood
Change in lathosterol levels in blood will be quantified after surgical resection.
Time frame: From start of treatment through day 16
Changes in zymostenol levels in blood
Change in zymostenol levels in blood will be quantified after 5 days of DSP-0390 dosing.
Time frame: From start of treatment through 5 days of treatment
Changes in zymostenol levels in blood
Change in zymostenol levels in blood will be quantified after 10 days of DSP-0390 dosing.
Time frame: From start of treatment through 10 days of treatment
Changes in zymostenol levels in blood
Change in zymostenol levels in blood will be quantified after 11 days of DSP-0390 dosing.
Time frame: From start of treatment through 11 days of treatment
Changes in zymostenol levels in blood
Change in zymostenol levels in blood will be quantified after 15 days of DSP-0390 dosing.
Time frame: From start of treatment through day 15
Changes in zymostenol levels in blood
Change in zymostenol levels in blood will be quantified after surgical resection.
Time frame: From start of treatment through day 16
Changes in L/Z ratio in blood
Change in L/Z ratio in blood will be quantified after 5 days of DSP-0390 dosing.
Time frame: From start of treatment through 5 days of treatment
Changes in L/Z ratio in blood
Change in L/Z ratio in blood will be quantified after 10 days of DSP-0390 dosing.
Time frame: From start of treatment through 10 days of treatment
Changes in L/Z ratio in blood
Change in L/Z ratio in blood will be quantified after 11 days of DSP-0390 dosing.
Time frame: From start of treatment through 11 days of treatment
Changes in L/Z ratio in blood
Change in L/Z ratio in blood will be quantified after 15 days of DSP-0390 dosing.
Time frame: From start of treatment through day 15
Changes in L/Z ratio in blood
Change in L/Z ratio in blood will be quantified after surgical resection.
Time frame: From start of treatment through day 16
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