A phase I study of the safety and activity of K-001 in patients with advanced pancreatic ductal adenocarcinoma.
BMC Cancer
; 21(1): 672, 2021 Jun 07.
Article
em En
| MEDLINE
| ID: mdl-34098895
ABSTRACT
BACKGROUND:
Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease that lack of effective therapeutic drugs. K-001 is an oral antitumor drug made from active ingredients of marine microorganisms. The current study aimed to evaluate safety and antitumor activity of K-001 in patients with advanced PDAC.METHODS:
In this phase I, open-label trial, patients with advanced PDAC were recruited to a dose-escalation study in a standard 3 + 3 design. K-001 was administered twice daily in four-week cycles, and dose escalation from 1350 mg to 2160 mg was evaluated twice daily. Physical examination and laboratory tests were done at screening and then weekly. The safety, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) of K-001 were assessed while tumor response was estimated by Response Evaluation Criteria in Solid Tumor (RECIST).RESULTS:
Eighteen patients with advanced PDAC were screened, and twelve eligible patients were analyzed in the study. No DLT was observed. Totally, 47 adverse events (AEs) presented, and 14 drug-related AEs were reported in 7 patients, including 8 grade 1 events (57.1%) and 6 grade 2 events (42.9%). There was no grade 3 or 4 drug-related AE. In these 14 drug-related AEs, the most frequent ones were dyspepsia (21.4%), followed by flatulence, constipation, and hemorrhoid bleeding (above 10% of each). Among all 12 patients, 10 patients (83.3%) maintained stable disease (SD), and 2 patients (16.7%) had progressive disease (PD). The objective response rate (ORR) was 0% and the disease control rate (DCR) was 83.3%.CONCLUSIONS:
K-001 manifests satisfactory safety and tolerability, as well as meaningful antitumor activity in advanced PDAC patients. Further evaluation of K-001 in phase II/III appears warranted. TRIAL REGISTRATION NCT02720666 . Registered 28 Match 2016 - Retrospectively registered.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Produtos Biológicos
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Peptidoglicano
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Carcinoma Ductal Pancreático
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Organismos Aquáticos
Tipo de estudo:
Diagnostic_studies
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
BMC Cancer
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China