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

Phase 1Active Not RecruitingNCT03875287

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins35 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Solid Tumor

Interventions

DecitabineDRUG

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

CedazuridineDRUG

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 100 Years

Medical Language ↔ Plain English

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.

Locations (2)

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Outcomes

Primary Outcomes

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)

Time frame: 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).

Time frame: up to 2 years

Secondary Outcomes

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)

Time frame: 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.

Time frame: 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.

Time frame: 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

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.