The objective of this study is to investigate tolerability, safety, pharmacokinetics (PK) and efficacy of oral OKN-007 in participants with recurrent high-grade glioma.
Dose escalation/PK study (Phase Ib) will follow a traditional 3+3 design with evaluable participants enrolled at each dose level: Cohort 1 (1000mg, BID), Cohort 2, (1000mg, TID), and Cohort 3 (1500 mg, TID). The food-effect study will be one-week add-on study at the beginning of the dose escalation/PK study. Dose expansion study (Phase 2) will proceed to treat at the maximum tolerated dose (MTD) up to 2 years or until tumor progression, unacceptable toxicity, death or participants withdrawal. Participant may continue receiving treatment beyond 2 years at the discretion of investigator.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Dose escalation/PK cohort (Phase Ib): 1000mg twice daily (BID), 1000mg thrice daily (TID), 1500mg thrice daily (TID). Expansion cohort (Phase 2): MTD defined in the dose escalation (Phase Ib) study.
Number of Participants with DLTs (Dose Limiting Toxicities) and AEs (Adverse Events)
It will be summarized by dose cohort and by overall safety evaluable population using CTCAE v5.0 for Phase Ib dose escalation and Phase 2 dose expansion cohort.
Time frame: 28 days
Number of Participants with Best Overall Response Rate in the brain
The rate of participants with complete response of partial response using Response Assessment in Neuro-Oncology Criteria (RANO) will be summarized for Phase 2 dose expansion cohort.
Time frame: 24 months
Proportion of Participants as Assessed by 6-month Progression-Free Survival (PFS)
Proportion of participants who are progression free after six months will be calculated for Phase Ib dose escalation and Phase 2 dose expansion cohort.
Time frame: 6 months
Proportion of Participants as Assessed by Overall Survival (OS)
Proportion of participants who are alive will be calculated as the time (days) from Day 1 to the participant's death for Phase Ib dose escalation and Phase 2 dose expansion cohort.
Time frame: 24 months
The Cmax of OKN-007 in plasma
Blood samples will be collected at 10 time points during the 47.5 hours for Phase Ib dose escalation cohort.
Time frame: Day 1 and Day 14
The Tmax (time to maximum concentration) of OKN-007 in plasma
Blood samples will be collected at 10 time points during the 47.5 hours for Phase Ib dose escalation cohort.
Time frame: Day 1 and Day 14
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AUC (area under the time curve) of OKN-007 in plasma
Blood samples will be collected at 10 time points during the 47.5 hours for Phase Ib dose escalation cohort.
Time frame: Day 1 and Day 14
Plasma concentration of OKN-007
Blood samples will be collected for participants enrolled in Phase 2 expansion cohort.
Time frame: Before the first dose on Day 8 and before the first dose of Day 29 in the morning
OKN-007 plasma levels over time for food-effect study
Blood samples will be collected on prior to dosing and at the following samples after OKN-007 single dose during 47.5 hours for participants enrolled in the food-effect study in Phase Ib dose escalation cohort.
Time frame: Day 7 and Day 4 before the beginning of the dose escalation/PK study