Dose-Escalation Study of E7727, an Oral Cytidine Deaminase Inhibitor With Oral Decitabine in Subjects With Solid Tumors
- Registration Number
- NCT03875287
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 35
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Decitabine and Cedazuridine Decitabine 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. Decitabine and Cedazuridine 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.
- Primary Outcome Measures
Name Time Method 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)
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
Name Time Method 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)
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.
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
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.
Trial Locations
- Locations (2)
USC Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
🇺🇸Baltimore, Maryland, United States