A phase 1 dose-escalation and dose-expansion study to assess the safety and efficacy of CKD-516, a novel vascular disrupting agent, in combination with Irinotecan in patients with previously treated metastatic colorectal cancer
- Authors
- Jeong, H[Jeong, Hyehyun]; Hong, YS[Hong, Yong Sang]; Kim, JE[Kim, Jeong Eun]; Lim, HS[Lim, Hyeong-Seok]; Ahn, JB[Ahn, Joong Bae]; Shin, SJ[Shin, Sang Joon]; Park, YS[Park, Young Suk]; Kim, ST[Kim, Seung Tae]; Han, SW[Han, Sae-Won]; Kim, TY[Kim, Tae-You]; Kim, TW[Kim, Tae Won]
- Issue Date
- Oct-2021
- Publisher
- SPRINGER
- Keywords
- Colorectal cancer; Vascular-disrupting agent; CKD-516; Irinotecan
- Citation
- INVESTIGATIONAL NEW DRUGS, v.39, no.5, pp.1335 - 1347
- Indexed
- SCIE
SCOPUS
- Journal Title
- INVESTIGATIONAL NEW DRUGS
- Volume
- 39
- Number
- 5
- Start Page
- 1335
- End Page
- 1347
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/2013
- DOI
- 10.1007/s10637-021-01110-9
- ISSN
- 0167-6997
- Abstract
- Introduction The combination of an anti-angiogenic agent with cytotoxic chemotherapy is a standard treatment strategy for metastatic colorectal cancer. CKD-516 is an oral vascular disrupting agent that was preliminarily shown to be safe and efficacious as a monotherapy in refractory solid cancers. We evaluated the recommended phase 2 dose, safety, and preliminary efficacy of CKD-516 in combination with irinotecan in treatment-refractory metastatic colorectal cancer. Methods This phase 1 dose-escalation and dose-expansion study included patients with treatment-refractory metastatic colorectal cancer. CKD-516 tablets were administered for five consecutive days followed by two days off in combination with intravenous irinotecan (120 mg/m(2)) administered on day one of each treatment cycle every two weeks. A traditional 3 + 3 dose-escalation design was used. Results In total, 16 and 23 patients were enrolled in the dose-escalation and dose-expansion cohorts, respectively. The most common adverse events included diarrhea (79%), nausea (74%), vomiting (67%), and neutropenia (62%). No dose-limiting toxicity occurred, and the recommended phase 2 dose was determined at CKD-516/irinotecan doses of 11/120 mg/m(2). No cases of cardiac ischemia, cardiac dysfunction, or thromboembolism were reported. Among the 34 patients with available tumor response assessments, one patient achieved partial response (3%) and 26 patients achieved stable disease (76%). The median progression-free survival and overall survival were 4.1 and 11.6 months, respectively. Conclusion This phase 1 study showed that the combination of oral CKD-516 and irinotecan is safe and tolerable in metastatic, treatment-refractory colorectal patients and showed favorable efficacy outcomes. Further studies to confirm these preliminary findings are warranted. Trial registration number NCT03076957 (Registered at March 10, 2017).
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