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

Phase I Clinical Trial to Assess the Safety and Pharmacokinetic Profile of CKD-516 Inj. Administered on A Twice-Weekly Schedule in Patients With Advanced Solid Cancers Failed to Standard Therapy

A phase I study is conducted to determine the maximum tolerated dose (MTD), dose limiting toxicity (DLT), safety and pharmacokinetics (PK) profile of a single agent CKD-516 injection on twice-weekly schedule in patients with advanced solid cancers failed to standard therapy. The usefulness of the this regimen is evaluated by response rate, progression free survival and vascular disruption effect by Dynamic Contrast-Enhanced MRI (DCE-MRI) or DWI.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: CKD-516 inj.

Detailed Description

This is an open label, dose escalation study. Patients receive CKD-516 IV over 30 minutes on day 1, 4, 8, 11 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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)
• serum creatinine ≤ 1.5×ULN or Creatinine clearance ≥ 60 mL/min
• PT, APTT: normal range
• 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
• Uncontrolled hypertension(greater than 150 mmHg systolic or 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 3 weeks prior to first dose of study drug(6 weeks for nitrosoureas and mitomycin C, 2 weeks for radiation therapy)
• Other concurrent antitumor therapy
• Patients with serious hypersensitivity history or allergy to CKD-516
• 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
• Patients judged to be inappropriate for this study by the investigator with other reasons

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: CKD-516 inj.; CKD-516 Inj, 3.3~13mg/m2/day, D1, 4, 8, 11 every 3 weeks	Drug: CKD-516 inj.; CKD-516: 3.3~13mg/m2/day; Other Names: CKD-516

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
MTD, Maximum Tolerated Dose	up to 21days

Secondary Outcome Measures

Outcome Measure	Time Frame
PK parameter of CKD-516	0(Pre-dose), 24hrs post dose (Day 1), 0, 0.5, 4, 8, 24hours post-dose(Day 11)
DLT, Dose-limiting Toxicity	up to 21days
ORR%, Objective response rate	up to 42weeks
Vascular disruption effect	4hr, 24hr post-dose

Collaborators and Investigators

• Sponsor: Chong Kun Dang Pharmaceutical
• Investigators: Principal Investigator: Yung-Jue Bang, Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: March 19, 2012
• First Submitted That Met QC Criteria: March 20, 2012
• First Posted (Estimate): March 22, 2012

Study Record Updates

• Last Update Posted (Estimate): September 16, 2015
• Last Update Submitted That Met QC Criteria: September 15, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Solid Tumor, Tubulin inhibitor
• Other Study ID Numbers: 127ASC12A