NOV120401 (CKD-516 Tablet) for Advanced Solid Tumors

Advanced Refractory Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02300467
• Other study ID #: NOV120401-101
• Status: Recruiting
• Phase: Phase 1
• First received: November 18, 2014
• Last updated: August 13, 2015
• Start date: December 2014
• Est. completion date: July 2016

Study information

• Verified date: August 2015
• Source: National OncoVenture
• Contact: Hark Kyun Kim, MD, PhD
• Email: hkim[@]ncc.re.kr
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Refractory Solid Tumors

Intervention

Drug:
• NOV120401
5 to 45 mg/day PO for 5 consecutive days and 2 days off

Locations

Country	Name	City	State
Korea, Republic of	National Cancer Center	Goyang-si	Gyeonggi-do

Sponsors (2)

Lead Sponsor	Collaborator
National OncoVenture	Chong Kun Dang Pharmaceutical

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Pharmacokinetic profiles (Cmax, Tmax, AUClast, AUCinf, t1/2, CL, MRT, Ctrough) of CKD-516 and S516 (active metabolite of CKD-516)		21 days	No
Secondary	Tumor response		up to 36 weeks	No
Secondary	Vascular disrupting activity measured by tubulin status (western blot from peripheral blood mononuclear cell)	western blot from peripheral blood mononuclear cell	21 days	No
Secondary	Vascular disrupting activity measured by plasma factor (VEGF, G-CSF, GM-CSF, SDF-1) concentration from serum	concentration from serum	21 days	No