Safety Study of Increasing Doses of CKD-516 in Patients With Advanced Solid Cancers

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.

Inclusion criteria

• 20~75 years
• Histologically or cytologically confirmed solid tumors that have failed to standard therapy or for which no life prolonging treatment exists
• ECOG PS 0-2
• Life expectancy 12 weeks
• Hematopoietic: ANC ≥ 1,500/mm3, Platelet ≥ 100,000/mm3, Hemoglobin ≥ 9.0g/dL, Prothrombin time, Activated partial thromboplastin time: normal range
• Hepatic: total bilirubin ≤ 1.5×ULN(except Gilbert's syndrome patients), AST, ALT ≤ 3.0×ULN(AST, ALT ≤ 5.0×ULN in case of liver metastases)
• Renal: serum creatinine ≤ 1.5×ULN or Creatinine clearance ≥ 60 mL/min
• Signed a written informed consent

Exclusion criteria

• Brain or Leptomeningeal metastases
• History of Ischemic heart disease(e.g., myocardial infarction, unstable angina pectoris) or Clinically significant heart disease such as NYHA Class III and IV Congestive atrial arrhythmias, within 6 months prior to first dose of study drug
• Stable angina pectoris shown symptoms within 6 months prior to first dose of study durg, or Clinically significant abnormality on EKG or echocardiogram(e.g., LVEF < 50% or clinically significant heart wall abnormality or heart muscle damage)
• Cerebrovascular disease such as stroke
• Grade 2 or greater motor or sensory peripheral neuropathy
• Clinically significant eye diseases(e.g., Glaucoma or Proliferative diabetic retinopathy, Atrophic macular degeneration), or other clinically significant abnormality on screening visit
• Uncontrolled hypertension(greater than 150 mmHg systolic anc 100 mmHg diastolic regardless of medication)
• acute infection or blooding tendencies that would preclude study compliance
• Serious vascular disease such as Aortic aneurysm
• Other psychiatric disorders or other conditions that would preclude study compliance
• Receiving anticoagulation with warfarin, heparin, etc.
• Receiving antitumor therapy(surgery, immunotherapy or chemotherapy) within 4 weeks prior to first dose of study drug(6 weeks for nitrosoureas and mitomycin C, 2 weeks for radiation therapy)
• Other concurrent antitumor therapy
• History of Serious hypersensitivity or allergy
• Pregnant or nursing, active serum pregnancy test. Fertile patients must use effective contraception
• Participation in a clinical trial within 4 weeks of first dose of study drug