NOV120401 (CKD-516 Tablet) for Advanced Solid Tumors

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

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.

Study Overview

• Status: Unknown
• Conditions: Advanced Refractory Solid Tumors
• Intervention / Treatment: Drug: NOV120401

Detailed Description

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
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, Korea, Republic of, 410-769
      • Recruiting
      • National Cancer Center
      • Contact: Hark Kyun Kim, MD, PhD; Email: hkim@ncc.re.kr
      • Principal Investigator: Hark Kyun Kim, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female patients aged 19 years or older
2. Patients who failed existing anti-cancer therapies
3. ECOG performance status ≤ 2
4. Life expectancy of ≥ 12 weeks
5. Adequate hematological, hepatic and renal functions:
6. Patients who give written informed consent voluntarily

Exclusion Criteria:

1. 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)
2. 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)
3. 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.)
4. 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)
5. Acute coronary syndrome (unstable angina or myocardial infarction) within 6 months
6. Uncontrolled arrhythmia
7. Significant cerebrovascular diseases including stroke within 6 months
8. Significant vascular diseases including aortic aneurysm requiring treatment or peripheral arterial diseases
9. Patients with known active hepatitis, HIV infection, or other uncontrolled infectious disease
10. 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
11. A history of severe drug hypersensitivity or hypersensitivity to analogs of the IP
12. Pregnancy or breast-feeding
13. 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
14. Patients who received other investigational products or used other investigational devices within 3 weeks before participation
15. Patients who cannot participate in this trial by investigator's discretion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National OncoVenture
• Collaborators: Chong Kun Dang Pharmaceutical
• Investigators: Study Director: Jung Yong Kim, MD, National OncoVenture (jyk1949@ncc.re.kr); Study Director: Min Chae Kim, Pharmacist, National OncoVenture (minchae@ncc.re.kr)

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Anticipated): July 1, 2016
• Study Completion (Anticipated): July 1, 2016

Study Registration Dates

• First Submitted: November 18, 2014
• First Submitted That Met QC Criteria: November 24, 2014
• First Posted (Estimate): November 25, 2014

Study Record Updates

• Last Update Posted (Estimate): August 14, 2015
• Last Update Submitted That Met QC Criteria: August 13, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: NOV120401-101