Clinical trial NCT03875287: Dose-Escalation Study of E7727, an Oral Cytidine Deaminase Inhibitor With Oral Decitabine in Subjects With Solid Tumors
Official title: A Phase I Dose-Escalation Study of E7727, an Oral Cytidine Deaminase Inhibitor (CDAi) With Oral Decitabine in Subjects With Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Solid Tumor
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Astex Pharmaceuticals, Inc.
First posted: 2019-03-14
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: OTHER

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Safety and tolerability of combination cedazuridine with decitabine as assessed by number of participants who experience adverse events
timeFrame: up to 2 years
measure: Maximum Tolerated Dose (MTD) as determined by number of participants with of dose limiting toxicities (DLT)
timeFrame: up to 2 years
Secondary outcomes:
measure: Pharmacokinetics of ASTX727 in solid tumor patients as measured by total exposure
timeFrame: Day 2
measure: Pharmacokinetics of ASTX727 in solid tumor patients as measured by maximum concentration (Cmax)
timeFrame: Day 2
measure: Pharmacokinetics of ASTX727 in solid tumor patients as measured by time to maximum concentration (Tmax)
timeFrame: Day 2
measure: Objective response rate (ORR) in solid tumor patients who are treated with ASTX727
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Nilofer Azad, MD
role: PRINCIPAL_INVESTIGATOR
References: