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
- 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).
- Author(s)
- 김승태; 김정은; 김태원; 김태유; 박용석; 신상준; 안중배; 임형석; 정혜현; 한세원; 홍용상
- Issued Date
- 2021
- Type
- Article
- Keyword
- CKD-516; Colorectal cancer; Irinotecan; Vascular-disrupting agent
- DOI
- 10.1007/s10637-021-01110-9
- URI
- https://oak.ulsan.ac.kr/handle/2021.oak/8181
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_proquest_miscellaneous_2510252604&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,A%20phase%201%20dose-escalation%20and%20dose-expansion%20study%20to%20assess%20the%20safety%20and%20efficacy%20of%20CKD-516,%20a%20novel%20vascular%20disrupting%20agent,%20in%20combination%20with%20Irinotecan%20in%20patients%20with%20previously%20treated%20metastatic%20colorectal%20cancer&offset=0&pcAvailability=true
- Publisher
- INVESTIGATIONAL NEW DRUGS
- Location
- 미국
- Language
- 영어
- ISSN
- 0167-6997
- Citation Volume
- 39
- Citation Number
- 5
- Citation Start Page
- 1335
- Citation End Page
- 1347
-
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