A Phase 1b/2a Study to Evaluate the Safety, Pharmacokinetics, and Objective Response of STAR-001 (LP-184) in Combination With Spironolactone in Supratentorial Glioblastoma at First Progression
brief summary
Approximately 58-68 total subjects will be enrolled. In the first stage, 10 response evaluable subjects (either IDHwt or IDHm Grade 4 astrocytoma) will be enrolled. If 1 or more of the first 10 response evaluable subjects achieve an objective response, 19 further subjects may be accrued in the second stage (for a total of 29 response evaluable subjects). Subjects enrolling in the study will provide fresh (in subjects who undergo a planned tumor resection) or archival (all subjects) tumor tissue sample (at least 10 unstained slides of 5-micron thickness) at screening for retrospective exploratory biomarker analysis and determination of intertumoral PTGR1 levels. STAR-001 (LP-184) will be administered via IV infusion over 30 minutes on Day 1 and Day 8 of each 21-day cycle. The STAR-001 dose for this study is 0.39 mg/kg. Spironolactone will be administered orally on Day (-2), Day (-1), and between 4-8 hours before the STAR-001 infusion on D1 (Day of STAR-001 IV infusion) and on Day 6, Day 7, and between 4-8 hours before the STAR-001 infusion on Day 8 . The spironolactone dose for this study is 100 mg given 3 times prior to STAR-001 infusion.
detailed description
Patients will continue to receive treatment based on response assessment and tolerability. Patients with disease control after Cycle 1 may continue treatment with STAR-001 (LP-184) if, in the opinion of the investigator, the patient is deriving clinical benefit from continuing study treatment. Patients may continue therapy for up to two years, or withdrawal for reasons of progressive disease on imaging, clinical progression, ≥Grade 4 AEs, withdrawal of consent, loss to follow-up, protocol violation, or at the discretion of the investigator.
Treatment beyond one year, if determined by the investigator to be of clinical benefit, requires consultation with and approval by the sponsor.
After treatment has been discontinued, an end-of-treatment visit will occur 30 days (+7 days) after the final dose. Patients are to be followed for survival (via telephone contact or review of medical records every 3 months.