Clinical trial NCT02300467: NOV120401 (CKD-516 Tablet) for Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced Refractory Solid Tumors
Lead sponsor: National OncoVenture
Sponsor class: OTHER
Collaborators: name: Chong Kun Dang Pharmaceutical
First posted: 2014-11-25
Enrollment: 30
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety and MTD/recommended phase 2 dose (RP2D) determination (Number of Participants with Adverse Events)
timeFrame: By 40 weeks after enrollment of the last subject
Secondary outcomes:
measure: Pharmacokinetic profiles (Cmax, Tmax, AUClast, AUCinf, t1/2, CL, MRT, Ctrough) of CKD-516 and S516 (active metabolite of CKD-516)
timeFrame: 21 days
measure: Tumor response
timeFrame: up to 36 weeks
measure: Vascular disrupting activity measured by tubulin status (western blot from peripheral blood mononuclear cell)
timeFrame: 21 days
measure: Vascular disrupting activity measured by plasma factor (VEGF, G-CSF, GM-CSF, SDF-1) concentration from serum
timeFrame: 21 days
Other outcomes:
Locations:
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
Study officials:
affiliation: National OncoVenture (jyk1949@ncc.re.kr)
name: Jung Yong Kim, MD
role: STUDY_DIRECTOR
affiliation: National OncoVenture (minchae@ncc.re.kr)
name: Min Chae Kim, Pharmacist
role: STUDY_DIRECTOR
References: