Study to Evaluate the Pharmacokinetics and Safety of Oral Decitabine and Cedazuridine in Cancer Patients With Hepatic Impairment
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorTaiho Oncology, Inc.
About this trial
This is a Phase 1b, multicenter, open-label, pharmacokinetic (PK), and safety study of multiple oral doses of oral decitabine and cedazuridine (formerly known as ASTX727) as a fixed-dose combination of decitabine 35 milligrams (mg) and cedazuridine 100 mg in cancer participants with moderate and severe hepatic impairment and cancer participants with normal hepatic function as control participants. Participants with severe hepatic impairment will be enrolled only after the safety evaluation of at least 6 participants with moderate hepatic impairment has been determined and supports the enrollment of participants with severe hepatic impairment. Adult participants with acute myeloid lymphoma (AML), myelodysplastic syndrome (MDS), or solid tumors who are candidates to receive oral decitabine and cedazuridine will be enrolled in this study. Study duration is per participant approximately up to 8 weeks.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Able to understand and comply with the study procedures, understand the risks involved in the study, and provide legally effective informed consent before the first study-specific procedure; specifically able to comply with the PK assessment schedule during the first treatment cycle.
A solid tumor that is metastatic or unresectable and for which standard life-prolonging measures are not available.
AML or MDS. or
A hematologic malignancy other than AML or MDS for which standard life-prolonging measures are not available.
Disqualifiers
Treatment with azacitidine or decitabine within 4 weeks before screening. Prior cytotoxic chemotherapy for AML except for hydroxyurea to control high white blood cell (WBC) counts.
Hospitalization for more than 2 days for documented febrile neutropenia, pneumonia, sepsis, or systemic infection 30 days prior to first dose.
Treatment with any investigational medicinal product (IMP), investigational therapy, chemotherapy, immunotherapy, or targeted therapy within 2 weeks or 5 half-lives, whichever is longer, before the first dose of study treatment, or ongoing clinically significant adverse events from previous treatment.
Concurrent MDS therapies, including lenalidomide, erythropoietin, cyclosporine/tacrolimus, granulocyte-colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor, etc. Prior treatment with these agents is permitted, provided that completion is at least 1 week before the first dose of study treatment. Short-term use of G-CSF for febrile neutropenia is permitted at the discretion of the treating physician and should be guided by accepted practice or institutional guidelines. Hematopoietic growth factors will not be routinely used unless cleared by Taiho medical expert.
Trial design
Design model
Parallel
Treatments tested in this trial
ASTX727
DrugMultiple-dose oral administration of once-daily decitabine (35 mg) and cedazuridine (100 mg)
Treatment groups
27 Participants
are divided into 3 treatment groupsGroup A: Group B: Moderate hepatic impairmentExperimental treatment 1 intervention
Group B: Group C: Severe hepatic impairmentExperimental treatment 1 intervention
Group C: Group A: Normal hepatic functionActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
Pharmacokinetic Parameter: 5-day Cumulative Area Under the Concentration-time Curve Within 1 Dosing Interval (AUCtau)
AUCtau from Day 1 to Day 5 for decitabine.
Time frame
Predose and at multiple timepoints post-dose from Day 1 to Day 5Secondary outcomes
1
Pharmacokinetic Parameter: Apparent Clearance (CL/F)
CL/F of decitabine and cedazuridine.
Time frame
Predose from Day 1 to Day 5 and at multiple timepoints post-dose from Day 1 to Day 82
Pharmacokinetic Parameter: Renal Clearance (CLR)
CLR of decitabine, cedazuridine, and cedazuridine-epimer.
Time frame
Predose from Day 1 to Day 5 and at multiple timepoints post-dose from Day 1 to Day 83
Pharmacokinetic Parameter: Apparent Nonrenal Clearance (CLNR/F)
CLNR/F of decitabine and cedazuridine.
Time frame
Predose from Day 1 to Day 5 and at multiple timepoints post-dose from Day 1 to Day 84
Pharmacokinetic Parameter: Time to Maximum Observed Plasma Concentration (Tmax)
Tmax of decitabine, cedazuridine, and cedazuridine-epimer.
Time frame
Predose from Day 1 to Day 5 and at multiple timepoints post-dose from Day 1 to Day 8Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov