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

Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
Overall Status
Recruiting
CT.gov ID
NCT03875287
Collaborator
Astex Pharmaceuticals, Inc. (Industry)
30
Enrollment
2
Locations
1
Arm
44.5
Anticipated Duration (Months)
15
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or DiseaseIntervention/TreatmentPhase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
30 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
A Phase I Dose-Escalation Study of E7727, an Oral Cytidine Deaminase Inhibitor (CDAi) With Oral Decitabine in Subjects With Solid Tumors
Actual Study Start Date :
Apr 17, 2019
Anticipated Primary Completion Date :
Jan 1, 2023
Anticipated Study Completion Date :
Jan 1, 2023

Arms and Interventions

ArmIntervention/Treatment
Experimental: Decitabine and Cedazuridine

Treatment 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.

Drug: Decitabine
DOSING REGIMEN(S): Level -1 10mg daily days 1-4 Level 1 10mg daily days 1-5 Level 2 15mg daily days 1-5 Level 3 20mg daily days 1-5
Other Names:
  • Dacogen
  • Drug: Cedazuridine
    DOSING REGIMEN(S): Level -1 100mg daily days 1-4 Level 1 100mg daily days 1-5 Level 2 100mg daily days 1-5 Level 3 100mg daily days 1-5

    Outcome Measures

    Primary Outcome Measures

    1. Safety and tolerability of combination cedazuridine with decitabine as assessed by number of participants who experience adverse events [up to 2 years]

      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)

    2. Maximum Tolerated Dose (MTD) as determined by number of participants with of dose limiting toxicities (DLT) [up to 2 years]

      Maximum tolerated dose will be determined by the maximum dose at which the least number of participants experience dose-limiting toxicity. The dose limiting toxicity is defined using the Common Terminology Criteria for Adverse Events (CTCAE).

    Secondary Outcome Measures

    1. Pharmacokinetics of ASTX727 in solid tumor patients as measured by total exposure [Day 2]

      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)

    2. Pharmacokinetics of ASTX727 in solid tumor patients as measured by maximum concentration (Cmax) [Day 2]

      Cmax (mmol/L) is defined as the maximum concentration of ASTX727 in blood.

    3. Pharmacokinetics of ASTX727 in solid tumor patients as measured by time to maximum concentration (Tmax) [Day 2]

      Tmax (minutes) is defined as the time to reach maximum concentration of ASTX727 in blood.

    4. Objective response rate (ORR) in solid tumor patients who are treated with ASTX727 [up to 2 years]

      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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 100 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1USC Norris Comprehensive Cancer CenterLos AngelesCaliforniaUnited States90089
    2Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimoreMarylandUnited States21231

    Sponsors and Collaborators

    • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Astex Pharmaceuticals, Inc.

    Investigators

    • Principal Investigator: Nilofer Azad, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    ClinicalTrials.gov Identifier:
    NCT03875287
    Other Study ID Numbers:
    • J18115
    • IRB00182038
    • ASTX727
    First Posted:
    Mar 14, 2019
    Last Update Posted:
    Nov 22, 2021
    Last Verified:
    Aug 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Nov 22, 2021