A phase I study is conducted to determine the maximum tolerated dose (MTD), dose limiting toxicity (DLT), safety and pharmacokinetics (PK) profile of a single agent CKD-516 injection on a weekly schedule in patients with advanced solid cancers failed to standard therapy. The usefulness of the this regimen is evaluated by response rate, progression free survival and vascular disruption effect by Dynamic Contrast-Enhanced MRI (DCE-MRI).
OBJECTIVES: * I. Determine the maximum tolerated dose of CKD-516 administered at single doses every 21 days in patients with advanced solid tumors. * II. Determine both the toxicity and dose limiting toxicity of this regimen in these patients. * III. Determine the plasma and urine pharmacokinetics of CKD-516. * IV. Gather preliminary data regarding possible antitumor effects in those patients with measurable diseae. Assess the effects of CKD-516 on tumor blood flow using DCE-MRI scanning techniques, and establish the dose at which these effects occur. OUTLINE: This is an open label, dose escalation study. Patients receive CKD-516 IV over 30 minutes on day 1, 8 every 3 weeks in the absence of unacceptable toxicity or disease progression. Cohorts of 3\~6 patients receive escalating doses of CKD-516 until the maximum tolerated dose(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicity.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
5.0 mg/2ml; 1.0, 2.0, 3.3, 5, 7, 9 \~ mg/m2; Day 1, Day 8 every 3 weeks
Seoul National University Hospital
Seoul, South Korea
MTD, Maximum Tolerated Dose
Time frame: 1st cycle
PK parameters of CKD-516 and its metabolite, S516, when CKD-516 administered on Days 1 and 8 of a 21-day cycle
Time frame: 1st cycle
Dose-limiting Toxicity
Time frame: 1st cycle
ORR%, Objective response rate
Time frame: every 2 cycle
PFS, Progression Free Survival
Time frame: 30 days before or after last patient out
Vascular disruption effect(with DCE-MRI)
Time frame: 24hr after 1st cycle day 1 treatment
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