Solid Tumor
Conditions
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).
Interventions
DRUGDecitabine
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
DRUGCedazuridine
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
Sponsors
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Astex Pharmaceuticals, Inc.
Stand Up To Cancer
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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 |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORNilofer Azad, MD
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Outcome results
None listed