The purpose of this open-label, dose-escalation phase I trial is to evaluate the safety, tolerability and pharmacokinetic profiles and to assess the efficacy of NOV120401 (CKD-516 Tablet), a novel vascular disrupting agent, in patients with advanced refractory solid tumors.
Vascular disrupting agents are expected to kill cancer cells located in core of tumor tissues by disrupting microvascular structure of tumor. To assess the safety and tolerability of NOV120401 (CKD-516 Tablet), patients with advanced refractory solid tumors will be enrolled in this study. Initial dose of NOV120401 (CKD-516 Tablet) is 5 mg/day, which will be escalated until at least 2 of 6 subjects show dose-limiting toxicities (DLTs). Pharmacokinetic profiles and efficacy by tumor response and vascular disrupting activities will also be assessed.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
5 to 45 mg/day PO for 5 consecutive days and 2 days off
National Cancer Center
Goyang-si, Gyeonggi-do, South Korea
RECRUITINGSafety and MTD/recommended phase 2 dose (RP2D) determination (Number of Participants with Adverse Events)
Number of Participants with Adverse Events
Time frame: By 40 weeks after enrollment of the last subject
Pharmacokinetic profiles (Cmax, Tmax, AUClast, AUCinf, t1/2, CL, MRT, Ctrough) of CKD-516 and S516 (active metabolite of CKD-516)
Time frame: 21 days
Tumor response
Time frame: up to 36 weeks
Vascular disrupting activity measured by tubulin status (western blot from peripheral blood mononuclear cell)
western blot from peripheral blood mononuclear cell
Time frame: 21 days
Vascular disrupting activity measured by plasma factor (VEGF, G-CSF, GM-CSF, SDF-1) concentration from serum
concentration from serum
Time frame: 21 days
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