Early Phase 1 Window of Opportunity Study of Oral DSP-0390 in Grade II and III Gliomas
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.
• Either newly diagnosied, suspected lower grade glioma per radiographic features, or radiographic recurrence of a histologically confirmed grade II or III IDH-mutant glioma.
• Patient must be a candidate for surgical resection
• At least 18 years of age.
• Karnofsky ≥ 70%
• Adequate bone marrow and organ function as defined below:
‣ Absolute neutrophil count ≥ 1.5 K/cumm (patient may not use G-CSF or GM-CSF to achieve this ANC level)
⁃ Platelets ≥ 100 K/cumm
⁃ Hemoglobin ≥ 9 g/dL (patient may not receive transfusion or use erythropoietin to obtain this Hgb level)
⁃ Total bilirubin ≤ 1.5 x IULN (or ≤ 3 x IULN for patients with known Gilbert's syndrome)
⁃ AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
⁃ International normalized ratio (INR), prothrombin time (PT), partial thromboplastin time (PTT), or activated partial thromboplastin time (aPTT) ≤1.5 x ULN. The use of anticoagulants is permitted as long as the PT/(a)PTT is within therapeutic limits (according to the local institution standard) and the patient has been on a stable anticoagulant regimen for at least 2 weeks prior to Day 1.
⁃ Creatinine Clearance of ≥40 mL/min per Cockroft-Gault formula or by a 24 hour urine.
• If a patient is using an antiepileptic medication, the patient is on a stable dose and without seizures for 14 days prior to Day 1. The antiepileptic medication used must not fall under any prohibited therapy category as defined in the protocol.
• If the patient is receiving corticosteroids at baseline, the dose administered is stable or decreasing for at least 5 days prior to Day 1. A higher stable dose of corticosteroids, if used as hormone replacement therapy, may be allowed upon discussion with the sponsor-investigator.
• The effects of DSP-0390 on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (2 forms of acceptable contraception, including one barrier method) prior to study entry, for the duration of study participation, and for 6 months after the last dose of DSP-0390. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• Ability to understand and willingness to sign an IRB approved written informed consent document.