NOV120401 (CKD-516 Tablet) for Advanced Solid Tumors

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of NOV120401 (CKD-516 Tablet) in Patients With Advanced Refractory Solid Tumors

Conditions
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Advanced Refractory Solid Tumors

Intervention / Treatment
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* Drug: NOV120401


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients aged 19 years or older Patients who failed existing anti-cancer therapies ECOG performance status ≤ 2 Life expectancy of ≥ 12 weeks Adequate hematological, hepatic and renal functions: Patients who give written informed consent voluntarily Exclusion Criteria: Prior systemic chemo-, radiochemo-, radio-, immuno-, hormonal and/or biological therapy within 2 weeks before study participation (in case of nitrosoureas and/or mitomycin, within 6 weeks before study participation) Patients who received major surgery within 4 weeks before study participation (in case of VATS and/or ONC surgery, within 2 weeks before study participation) Symptomatic CNS metastases (patients with radiologically and neurologically stable metastases and being off corticosteroids for at least 4 weeks are able to participate in this trial.) NYHA class III or IV heart failure, uncontrolled hypertension (SBP/DBP > 140/90 mm Hg), other clinically significant cardiovascular abnormalities at investigator's discretion (e.g., LVEF < 50%, clinically significant cardiac wall abnormalities or cardiac muscle damages) Acute coronary syndrome (unstable angina or myocardial infarction) within 6 months Uncontrolled arrhythmia Significant cerebrovascular diseases including stroke within 6 months Significant vascular diseases including aortic aneurysm requiring treatment or peripheral arterial diseases Patients with known active hepatitis, HIV infection, or other uncontrolled infectious disease Patients who cannot receive IP by mouth and have a history of clinically significant gastrointestinal disorders which can impede administration, transit or absorption of the IP A history of severe drug hypersensitivity or hypersensitivity to analogs of the IP Pregnancy or breast-feeding Women of childbearing potential (WOCBP) or men who are unwilling to use adequate contraception or be abstinent during the trial and for at least 2 months after the end of treatment Patients who received other investigational products or used other investigational devices within 3 weeks before participation Patients who cannot participate in this trial by investigator's discretion

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NOV120401 (CKD-516 Tablet)<br>5 to 45 mg/day PO for 5 consecutive days and 2 days off | Drug: NOV120401<br>* 5 to 45 mg/day PO for 5 consecutive days and 2 days off<br>* Other names: CKD-516 Tablet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and MTD/recommended phase 2 dose (RP2D) determination (Number of Participants with Adverse Events) | Number of Participants with Adverse Events | By 40 weeks after enrollment of the last subject | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profiles (Cmax, Tmax, AUClast, AUCinf, t1/2, CL, MRT, Ctrough) of CKD-516 and S516 (active metabolite of CKD-516) |  | 21 days | 
| Tumor response |  | 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 | 21 days | 
| Vascular disrupting activity measured by plasma factor (VEGF, G-CSF, GM-CSF, SDF-1) concentration from serum | concentration from serum | 21 days |