Phase I Study of CKD-516, a Novel Vascular Disrupting Agent, in Patients with Advanced Solid Tumors.
- Author:
Do Youn OH
1
;
Tae Min KIM
;
Sae Won HAN
;
Dong Yeop SHIN
;
Yun Gyoo LEE
;
Keun Wook LEE
;
Jee Hyun KIM
;
Tae You KIM
;
In Jin JANG
;
Jong Seok LEE
;
Yung Jue BANG
Author Information
- Publication Type:Original Article
- Keywords: CKD-516; Vascular disrupting agent; Phase I clinical trial; Solid tumor
- MeSH: Abdominal Pain; Disease-Free Survival; Humans; Hypertension; Male; Myalgia; National Cancer Institute (U.S.); Nausea; Pharmacokinetics; Vomiting
- From:Cancer Research and Treatment 2016;48(1):28-36
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: CKD-516 is a newly developed vascular disrupting agent. This phase I dose-escalation study of CKD-516 was conducted to determine maximum-tolerated dose (MTD), safety, pharmacokinetics, and preliminary antitumor efficacy in patients with advanced solid tumors. MATERIALS AND METHODS: Patients received CKD-516 intravenously on D1 and D8 every 3 weeks, in a standard 3+3 design. Safety was evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.02 and response was assessed by Response Evaluation Criteria in Solid Tumor ver. 1.1. RESULTS: Twenty-three patients were treated with CKD-516 at seven dosing levels: 1 mg/m2/day (n=3), 2 mg/m2/day (n=3), 3.3 mg/m2/day (n=3), 5 mg/m2/day (n=3), 7 mg/m2/day (n=3), 9 mg/m2/day (n=6), and 12 mg/m2/day (n=2). Mean age was 54 and 56.5% of patients were male. Two dose-limiting toxicities, which were both grade 3 hypertension, were observed in two patients at 12 mg/m2/day. The MTD was determined as 12 mg/m2/day. Most common adverse events were gastrointestinal adverse events (diarrhea, 34.8% [30.4% grade 1/2, 13.0% grade 3]; nausea, 21.7% [all grade 1/2]; vomiting, 21.7% [all grade 1/2]), myalgia (17.4%, all grade 1/2), and abdominal pain (21.7% [21.7% grade 1/2, 4.3% grade 3]). The pharmacokinetic study showed the dose-linearity of all dosing levels. Among 23 patients, six patients (26.1%) showed stable disease. Median progression-free survival was 39 days (95% confidence interval, 37 to 41 days). CONCLUSION: This study demonstrates feasibility of CKD-516, novel vascular disrupting agent, in patients with advanced solid tumor. MTD of CKD-516 was defined as 12 mg/m2/day on D1 and D8 every 3 weeks.
