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

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

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 35 patients total).

Study Overview

• Status: Active, not recruiting
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: Decitabine; Drug: Cedazuridine

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90089
      • USC Norris Comprehensive Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / 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 Level 4 25 mg 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 Level 4 100mg daily days 1-5

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of combination cedazuridine with decitabine as assessed by number of participants who experience adverse events	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)	up to 2 years
Maximum Tolerated Dose (MTD) as determined by number of participants with of dose limiting toxicities (DLT)	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).	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of ASTX727 in solid tumor patients as measured by total exposure	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)	Day 2
Pharmacokinetics of ASTX727 in solid tumor patients as measured by maximum concentration (Cmax)	Cmax (mmol/L) is defined as the maximum concentration of ASTX727 in blood.	Day 2
Pharmacokinetics of ASTX727 in solid tumor patients as measured by time to maximum concentration (Tmax)	Tmax (minutes) is defined as the time to reach maximum concentration of ASTX727 in blood.	Day 2
Objective response rate (ORR) in solid tumor patients who are treated with ASTX727	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	up to 2 years

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Astex Pharmaceuticals, Inc.; Stand Up To Cancer
• Investigators: Principal Investigator: Nilofer Azad, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2019
• Primary Completion (Estimated): March 2, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: March 13, 2019
• First Submitted That Met QC Criteria: March 13, 2019
• First Posted (Actual): March 14, 2019

Study Record Updates

• Last Update Posted (Actual): September 8, 2026
• Last Update Submitted That Met QC Criteria: September 4, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine; Decitabine; cedazuridine
• Other Study ID Numbers: J18115; IRB00182038 (Other Identifier: JHM IRB); ASTX727 (Other Identifier: Astex Pharmaceuticals)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No