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

NCT03875287 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: J18115IRB00182038ASTX727
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

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 35 patients total).

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Pharmacokinetics of ASTX727 in solid tumor patients as measured by total exposure

  Day 2

• Pharmacokinetics of ASTX727 in solid tumor patients as measured by maximum concentration (Cmax)

  Day 2

• Pharmacokinetics of ASTX727 in solid tumor patients as measured by time to maximum concentration (Tmax)

  Day 2

• Objective response rate (ORR) in solid tumor patients who are treated with ASTX727

  up to 2 years

Study Arms (1)

Decitabine and Cedazuridine

EXPERIMENTAL

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; Drug: Cedazuridine

Interventions

Decitabine DRUG

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

Also known as: Dacogen

Decitabine and Cedazuridine

Cedazuridine DRUG

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

Decitabine and Cedazuridine

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Astex Pharmaceuticals, Inc.: collaborator
• Stand Up To Cancer: collaborator

Study Sites (2)

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90089, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Interventions

Decitabine; cedazuridine

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Nilofer Azad, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2019
• First Posted: March 14, 2019
• Study Start: April 17, 2019
• Primary Completion (Estimated): September 2, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: January 12, 2026

Record last verified: 2026-01

Locations

US (2)