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

Chong Kun Dang

Status and phase

Completed

Phase 1

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Treatments

Drug: CKD-516 inj

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01028859

127ASC09E

Details and patient eligibility

About

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 a 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).

Full description

OBJECTIVES:

I. Determine the maximum tolerated dose of CKD-516 administered at single doses every 21 days in patients with advanced solid tumors.
II. Determine both the toxicity and dose limiting toxicity of this regimen in these patients.
III. Determine the plasma and urine pharmacokinetics of CKD-516.
IV. Gather preliminary data regarding possible antitumor effects in those patients with measurable diseae. Assess the effects of CKD-516 on tumor blood flow using DCE-MRI scanning techniques, and establish the dose at which these effects occur.

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

Enrollment

30 estimated patients

Sex

All

Ages

20 to 75 years old

Volunteers

No Healthy Volunteers

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)
Renal: serum creatinine ≤ 1.5×ULN or Creatinine clearance ≥ 60 mL/min
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
Clinically significant eye diseases(e.g., Glaucoma or Proliferative diabetic retinopathy, Atrophic macular degeneration), or other clinically significant abnormality on screening visit
Uncontrolled hypertension(greater than 150 mmHg systolic anc 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 4 weeks prior to first dose of study drug(6 weeks for nitrosoureas and mitomycin C, 2 weeks for radiation therapy)
Other concurrent antitumor therapy
History of Serious hypersensitivity or allergy
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