The Cancer Therapy Evaluation Program (CTEP) is accepting Letters of Intent (LOIs) to conduct clinical studies using ASTX727 (a combination of oral decitabine and cedazuridine) which is being developed by CTEP as an anticancer agent in collaboration with Astex Pharmaceuticals, Inc. All clinical and nonclinical researchers possessing an interest in working with the agent are welcome to apply. Proposals for clinical trials should be supported by a strong rationale and robust preclinical data (see “Components of a Competitive Letter of Intent” at http://ctep.cancer.gov/protocolDevelopment/lois_concepts.htm).
Decitabine (5-aza-2′-deoxycytidine) and azacitidine (5-azacitidine) are pyrimidine analogs of cytidine which at clinically relevant concentrations inhibit DNA methyltransferases (DNMTs), and result in transient and variable DNA hypomethylation, cellular differentiation, DNA damage, and apoptosis (Diesch et al., 2016, Duchmann et al., 2019). These compounds are often referred to as de-methylating or hypomethylating agents (HMAs). Cedazuridine is a synthetic nucleoside analog derived from tetrahydrouridine (THU), and functions as a cytidine deaminase inhibitor (CDAi) that is used to prevent the breakdown of cytidines and increase the oral bioavailability of cytidine analogs (Camiener, 1968; Savona et al., 2019).
All proposals approved by CTEP will be sent to the industry collaborator for a commitment to supply drug for the study.
For more information please see related documents below.