Pharmacokinetic Guided Dose Escalation and Dose Confirmation With Oral Decitabine and Oral CDAi in Patients With MDS

Official Title

A Phase1-2 Pharmacokinetic Guided Dose-Escalation and Dose-Confirmation Study of ASTX727, a Combination of the Oral Cytidine Deaminase Inhibitor (CDAi) E7727 With Oral Decitabine in Subjects With Myelodysplastic Syndromes (MDS)

Summary:

This 2-stage, open-label study will evaluate safety and pharmacokinetics of ASTX727, as well as determine the dose for the study's second stage. In the second stage the selected dose will be confirmed and evaluated for clinical activity, including response rate.

Trial Description

Primary Outcome:

  • Pharmacokinetics: plasma decitabine after oral decitabine and E7727 area under the plasma concentration versus time curve (AUC) by cohort.
  • Incidence of Dose limiting toxicities by cohort
  • Pharmacodynamics: Maximum %LINE-1 demethylation of ASTX727 compared to 20mg/m2 IV decitabine
  • Overall Response Rate
Secondary Outcome:
  • Pharmacokinetics: area under the plasma concentration versus time curve (AUC) of oral decitabine, E7727 and E7727-epimer
  • Pharmacodynamics: Mean maximum % demethylation of the LINE-1 elements in peripheral blood will be reported by cohort
  • Number and proportion of subjects with adverse events by type and grade
  • Pharmacokinetics: Maximum Plasma Concentration (Cmax) of oral decitabine, E7727 and E7727-epimer
  • Pharmacokinetics: Minimum Plasma Concentration (Cmin) of oral decitabine, E7727 and E7727-epimer
Dose levels for the study's second stage will be based on safety and pharmacokinetics.

View this trial on ClinicalTrials.gov

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Resources

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