Phase I study of procaspase-activating compound-1 (PAC-1) in the treatment of advanced malignancies.

ABSTRACT:

Background

Procaspase-3 (PC-3) is overexpressed in multiple tumour types and procaspase-activating compound 1 (PAC-1) directly activates PC-3 and induces apoptosis in cancer cells. This report describes the first-in-human, phase I study of PAC-1 assessing maximum tolerated dose, safety, and pharmacokinetics.

Methods

Modified-Fibonacci dose-escalation 3 + 3 design was used. PAC-1 was administered orally at 7 dose levels (DL) on days 1-21 of a 28-day cycle. Dose-limiting toxicity (DLT) was assessed during the first two cycles of therapy, and pharmacokinetics analysis was conducted on days 1 and 21 of the first cycle. Neurologic and neurocognitive function (NNCF) tests were performed throughout the study.

Results

Forty-eight patients were enrolled with 33 completing ≥2 c

SUBMITTER: Danciu OC 

PROVIDER: S-EPMC9977881 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature