Clinical Trials /

Dose-Escalation Study of E7727, an Oral Cytidine Deaminase Inhibitor (CDAi) With Oral Decitabine in Subjects With Solid Tumors

NCT03875287

Description:

This is a phase 1 study of the combination of cedazuridine with decitabine in patients with solid tumors. At least 6 patients will be enrolled per treatment level to assess optimal hypomethylation and toxicity (up to 30 patients total).

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Dose-Escalation Study of E7727, an Oral Cytidine Deaminase Inhibitor (CDAi) With Oral Decitabine in Subjects With Solid Tumors
  • Official Title: A Phase I Dose-Escalation Study of E7727, an Oral Cytidine Deaminase Inhibitor (CDAi) With Oral Decitabine in Subjects With Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: J18115
  • SECONDARY ID: IRB00182038
  • SECONDARY ID: ASTX727
  • NCT ID: NCT03875287

Conditions

  • Solid Tumor

Interventions

DrugSynonymsArms
DecitabineDacogenDecitabine and Cedazuridine
CedazuridineDecitabine and Cedazuridine

Purpose

This is a phase 1 study of the combination of cedazuridine with decitabine in patients with solid tumors. At least 6 patients will be enrolled per treatment level to assess optimal hypomethylation and toxicity (up to 30 patients total).

Trial Arms

NameTypeDescriptionInterventions
Decitabine and CedazuridineExperimentalTreatment will be administered on an outpatient basis. Cycle length is 28 days. The dose of cedazuridine is fixed at 100mg and the dose and duration of decitabine will vary depending on when a patient enters the study.
  • Decitabine
  • Cedazuridine

Eligibility Criteria

        Inclusion Criteria:

          -  Participants must have advanced, unresectable, and/or metastatic solid tumor
             malignancy that is histologically or cytologically confirmed.

          -  Patients must have received at least 2 lines of therapy in the advanced/metastatic
             setting (if 2 lines exist) and have no other possible therapies or refuse therapies
             that have shown clinical benefit for their condition.

          -  ECOG performance status <1

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Patients must have measurable disease

          -  Ability to swallow oral medications

        Exclusion Criteria:

          -  Participants who have had chemotherapy or radiotherapy within 3 weeks

          -  Participants may not be receiving any other investigational agents.

          -  Active hepatitis B or hepatitis C infection.

          -  Active or untreated gastric or duodenal ulcer

          -  Symptomatic bowel obstruction within 3 months prior to screening visit.

          -  Symptomatic ascites in the last 4 weeks

        Other protocol defined inclusion/exclusion criteria may apply.
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability of combination cedazuridine with decitabine as assessed by number of participants who experience adverse events
Time Frame:up to 2 years
Safety Issue:
Description:Number of participants who have experienced grade 3 or higher adverse events, as defined by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0)

Secondary Outcome Measures

Measure:Pharmacokinetics of ASTX727 in solid tumor patients as measured by total exposure
Time Frame:Day 2
Safety Issue:
Description:Total exposure will be calculated as area under the plasma concentration-time curve (AUC) by using non-compartmental methods (Winonlin, version 5.3 or newer) and/or compartmental modeling (Adapt II, release 4.0)
Measure:Pharmacokinetics of ASTX727 in solid tumor patients as measured by maximum concentration (Cmax)
Time Frame:Day 2
Safety Issue:
Description:Cmax (mmol/L) is defined as the maximum concentration of ASTX727 in blood.
Measure:Pharmacokinetics of ASTX727 in solid tumor patients as measured by time to maximum concentration (Tmax)
Time Frame:Day 2
Safety Issue:
Description:Tmax (minutes) is defined as the time to reach maximum concentration of ASTX727 in blood.
Measure:Objective response rate (ORR) in solid tumor patients who are treated with ASTX727
Time Frame:up to 2 years
Safety Issue:
Description:Proportion of participants who had measurable disease at baseline and have been re-evaluated after at least 1 cycle of therapy with observed reduction in tumor burden as defined by RECIST 1.1: Complete response (CR)= disappearance of all target lesions, Partial response (PR)= at least 30% decrease in sum of diameters of target lesions

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Last Updated

December 13, 2019