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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

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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)
김승태김정은김태원김태유박용석신상준안중배임형석정혜현한세원홍용상
Issued Date
2021
Type
Article
Keyword
CKD-516Colorectal cancerIrinotecanVascular-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
Appears in Collections:
Medicine > Medicine
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