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

Solid Tumor Clinical Trial

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03875287
• Other study ID #: J18115
• Secondary ID: IRB00182038ASTX7
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: April 17, 2019
• Est. completion date: December 2024

Study information

• Verified date: January 2024
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 29
• Est. completion date: December 2024
• Est. primary completion date: January 2, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

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
• 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

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Astex Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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