A phase i pharmacokinetic and pharmacodynamic study of CKD-732, an antiangiogenic agent, in patients with refractory solid cancer

Sang Joon Shin; Hei Cheul Jeung; Joong Bae Ahn; Sun Young Rha; Jae Kyung Roh; Kyung Soo Park; Dal Hyun Kim; Chin Kim; Hyun Cheol Chung

doi:10.1007/s10637-009-9287-8

A phase i pharmacokinetic and pharmacodynamic study of CKD-732, an antiangiogenic agent, in patients with refractory solid cancer

Sang Joon Shin, Hei Cheul Jeung, Joong Bae Ahn, Sun Young Rha, Jae Kyung Roh, Kyung Soo Park, Dal Hyun Kim, Chin Kim, Hyun Cheol Chung

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

Abstract

Summary: We conducted a phase I trial of the antiangiogenic agent 6-O-(4-dimethylaminoethoxy) cinnamoyl fumagillol hemioxalate (CKD-732). Our aims were to determine the maximum tolerated dose (MTD), pharmacokinetics (PK), and safety profiles as well as identify the biologically active dose (BAD) from ex vivo pharmacodynamics (PD) and biomarkers of CKD-732. Using a dose escalation schedule, 19 patients with refractory solid tumors were enrolled at dose levels of CKD-732 ranging from 1 to 15 mg/m² given twice weekly for 2 weeks followed by a 1-week rest. No treatment-related deaths occurred in this study. Confusion and insomnia were dose-limiting toxicities (DLTs), and MTD was 15 mg/m². The area under the concentration-time curve (AUC) and maximum concentration (Cmax) increased dose dependently with increasing doses. The BAD was 5 mg/m² according to ex vivo PD. A decrement in soluble vascular endothelial growth factor receptor-3 (sVEGF-3) level was correlated with a reduction in tumor size (r=0.54, P=0.045). The results from this study showed an MTD of 15 mg/m² and a BAD of 5 mg/m².

Original language	English
Pages (from-to)	650-658
Number of pages	9
Journal	Investigational New Drugs
Volume	28
Issue number	5
DOIs	https://doi.org/10.1007/s10637-009-9287-8
Publication status	Published - 2010 Oct

Bibliographical note

Funding Information:
Acknowledgements This work was supported by a Korea Science and Engineering Foundation (KOSEF) grant funded by the Ministry of Science and Technology (MOST) of Korea (R11-2000-082-02008-0) and grants from the Korean Ministry for Health, Welfare and Family Affairs (01-PJ1-PG4-01PT01-0004 and A050083). We thank Dong-Su Jang for his help with drawing the figures. Language editing was done by Sydney Sue Kim.

All Science Journal Classification (ASJC) codes

Oncology
Pharmacology
Pharmacology (medical)

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s10637-009-9287-8

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title = "A phase i pharmacokinetic and pharmacodynamic study of CKD-732, an antiangiogenic agent, in patients with refractory solid cancer",

abstract = "Summary: We conducted a phase I trial of the antiangiogenic agent 6-O-(4-dimethylaminoethoxy) cinnamoyl fumagillol hemioxalate (CKD-732). Our aims were to determine the maximum tolerated dose (MTD), pharmacokinetics (PK), and safety profiles as well as identify the biologically active dose (BAD) from ex vivo pharmacodynamics (PD) and biomarkers of CKD-732. Using a dose escalation schedule, 19 patients with refractory solid tumors were enrolled at dose levels of CKD-732 ranging from 1 to 15 mg/m2 given twice weekly for 2 weeks followed by a 1-week rest. No treatment-related deaths occurred in this study. Confusion and insomnia were dose-limiting toxicities (DLTs), and MTD was 15 mg/m2. The area under the concentration-time curve (AUC) and maximum concentration (Cmax) increased dose dependently with increasing doses. The BAD was 5 mg/m2 according to ex vivo PD. A decrement in soluble vascular endothelial growth factor receptor-3 (sVEGF-3) level was correlated with a reduction in tumor size (r=0.54, P=0.045). The results from this study showed an MTD of 15 mg/m2 and a BAD of 5 mg/m2.",

author = "Shin, {Sang Joon} and Jeung, {Hei Cheul} and Ahn, {Joong Bae} and Rha, {Sun Young} and Roh, {Jae Kyung} and Park, {Kyung Soo} and Kim, {Dal Hyun} and Chin Kim and Chung, {Hyun Cheol}",

note = "Funding Information: Acknowledgements This work was supported by a Korea Science and Engineering Foundation (KOSEF) grant funded by the Ministry of Science and Technology (MOST) of Korea (R11-2000-082-02008-0) and grants from the Korean Ministry for Health, Welfare and Family Affairs (01-PJ1-PG4-01PT01-0004 and A050083). We thank Dong-Su Jang for his help with drawing the figures. Language editing was done by Sydney Sue Kim.",

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AU - Rha, Sun Young

AU - Roh, Jae Kyung

AU - Park, Kyung Soo

AU - Kim, Dal Hyun

AU - Kim, Chin

AU - Chung, Hyun Cheol

N1 - Funding Information: Acknowledgements This work was supported by a Korea Science and Engineering Foundation (KOSEF) grant funded by the Ministry of Science and Technology (MOST) of Korea (R11-2000-082-02008-0) and grants from the Korean Ministry for Health, Welfare and Family Affairs (01-PJ1-PG4-01PT01-0004 and A050083). We thank Dong-Su Jang for his help with drawing the figures. Language editing was done by Sydney Sue Kim.

PY - 2010/10

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N2 - Summary: We conducted a phase I trial of the antiangiogenic agent 6-O-(4-dimethylaminoethoxy) cinnamoyl fumagillol hemioxalate (CKD-732). Our aims were to determine the maximum tolerated dose (MTD), pharmacokinetics (PK), and safety profiles as well as identify the biologically active dose (BAD) from ex vivo pharmacodynamics (PD) and biomarkers of CKD-732. Using a dose escalation schedule, 19 patients with refractory solid tumors were enrolled at dose levels of CKD-732 ranging from 1 to 15 mg/m2 given twice weekly for 2 weeks followed by a 1-week rest. No treatment-related deaths occurred in this study. Confusion and insomnia were dose-limiting toxicities (DLTs), and MTD was 15 mg/m2. The area under the concentration-time curve (AUC) and maximum concentration (Cmax) increased dose dependently with increasing doses. The BAD was 5 mg/m2 according to ex vivo PD. A decrement in soluble vascular endothelial growth factor receptor-3 (sVEGF-3) level was correlated with a reduction in tumor size (r=0.54, P=0.045). The results from this study showed an MTD of 15 mg/m2 and a BAD of 5 mg/m2.

AB - Summary: We conducted a phase I trial of the antiangiogenic agent 6-O-(4-dimethylaminoethoxy) cinnamoyl fumagillol hemioxalate (CKD-732). Our aims were to determine the maximum tolerated dose (MTD), pharmacokinetics (PK), and safety profiles as well as identify the biologically active dose (BAD) from ex vivo pharmacodynamics (PD) and biomarkers of CKD-732. Using a dose escalation schedule, 19 patients with refractory solid tumors were enrolled at dose levels of CKD-732 ranging from 1 to 15 mg/m2 given twice weekly for 2 weeks followed by a 1-week rest. No treatment-related deaths occurred in this study. Confusion and insomnia were dose-limiting toxicities (DLTs), and MTD was 15 mg/m2. The area under the concentration-time curve (AUC) and maximum concentration (Cmax) increased dose dependently with increasing doses. The BAD was 5 mg/m2 according to ex vivo PD. A decrement in soluble vascular endothelial growth factor receptor-3 (sVEGF-3) level was correlated with a reduction in tumor size (r=0.54, P=0.045). The results from this study showed an MTD of 15 mg/m2 and a BAD of 5 mg/m2.

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ER -

A phase i pharmacokinetic and pharmacodynamic study of CKD-732, an antiangiogenic agent, in patients with refractory solid cancer

Abstract

Bibliographical note

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