Study to Evaluate the Pharmacokinetics and Safety of Oral Decitabine and Cedazuridine in Cancer Patients With Hepatic Impairment

NCT04953910 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: ASTX727-182024-516292-33-00
• Study Type: interventional
• Target: 27
• Locations: 8 countries
• Sites: 22

Brief Summary

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.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndromes

Outcome Measures

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.

  Predose and at multiple timepoints post-dose from Day 1 to Day 5

Secondary Outcomes (15)

• Pharmacokinetic Parameter: Apparent Clearance (CL/F)

  Predose from Day 1 to Day 5 and at multiple timepoints post-dose from Day 1 to Day 8

• Pharmacokinetic Parameter: Renal Clearance (CLR)

  Predose from Day 1 to Day 5 and at multiple timepoints post-dose from Day 1 to Day 8

• Pharmacokinetic Parameter: Apparent Nonrenal Clearance (CLNR/F)

  Predose from Day 1 to Day 5 and at multiple timepoints post-dose from Day 1 to Day 8

• Pharmacokinetic Parameter: Time to Maximum Observed Plasma Concentration (Tmax)

  Predose from Day 1 to Day 5 and at multiple timepoints post-dose from Day 1 to Day 8

• Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax)

  Predose and at multiple time points post-dose on Days 1, 2 and 5

Study Arms (3)

Group B: Moderate hepatic impairment

EXPERIMENTAL

Cancer participants with moderate hepatic impairment \[total bilirubin \>1.5X - 3X upper limit of normal (ULN); any aspartate aminotransferase (AST) level\]

Drug: ASTX727

Group C: Severe hepatic impairment

EXPERIMENTAL

Cancer participants with severe hepatic impairment (\>3X ULN; any AST level)

Drug: ASTX727

Group A: Normal hepatic function

ACTIVE COMPARATOR

Cancer participants with normal hepatic function (total bilirubin ≤ULN; AST ≤ULN)

Drug: ASTX727

Interventions

ASTX727 DRUG

Multiple-dose oral administration of once-daily decitabine (35 mg) and cedazuridine (100 mg)

Also known as: Oral decitabine and cedazuridine

Group A: Normal hepatic function; Group B: Moderate hepatic impairment; Group C: Severe hepatic impairment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Participants must have a histologically or cytologically confirmed malignancy as follows:
• 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.
• For participants with AML/MDS only:
• Cytologically or histologically confirmed diagnosis of AML (except M3 acute promyelocytic leukemia) or MDS according to the 2008 World Health Organization (WHO) classification; or
• Participants with frontline MDS or treatment naïve AML not suitable for induction therapy (e.g., \>75 years, Eastern Cooperative Oncology Group \[ECOG\] performance status ≥2, severe pulmonary disorder, total bilirubin \>1.5X ULN; and
• Platelet count ≥25,000/per microliter (μ); and
• Absolute neutrophil count (ANC) ≥100 cells/μL.
• For participants only with hematologic malignancies other than AML or MDS, or with solid tumors:
• Platelet count ≥100,000/μL; and
• ANC ≥1000 cells/μL.
• ECOG performance status of 0 to 3.
• Hepatic function defined per the National Cancer Institute Cancer Therapy Evaluation Program (NCI CTEP) Organ Dysfunction Working Group (ODWG) as:

You may not qualify if:

• 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.
• Administration of live (attenuated) vaccines within 4 weeks before the first administration of oral decitabine and cedazuridine until after the follow-up visit. Other vaccines, e.g., inactivated or ribonucleic acid (RNA)-based, may be administered but should not occur from 7 days before first administration of oral decitabine and cedazuridine until after the follow-up visit.
• High medical risk because of other conditions such as uncontrolled systemic diseases, active uncontrolled infections, or comorbidities that may put the participant at risk of not being able to complete 1 cycle of treatment.
• Conditions which likely promote delayed ventricular repolarization (QT prolongation):
• QTc using Fridericia's correction (QTcF) at screening or Day -1 \>470 ms for males and \>480 ms for females.
• History or disposition for torsades des pointes (TdP) (e.g., heart failure, hypokalemia, family history of long QT Syndrome).
• Concomitant medications that prolong the QT/QTc interval.
• Cardiac abnormalities or unstable cardiovascular conditions:
• Unstable ischemic heart disease or severe heart failure (New York Heart Association Class III or IV).
• Uncontrolled treated/untreated hypertension (defined as a mean of 3 repeated measurements for systolic blood pressure ≥180 millimeters of mercury (mmHg) and/or diastolic blood pressure ≥110 mmHg; current or documented history of repeated clinically significant hypotension or severe episodes of orthostatic hypotension (systolic blood pressure \<90 mmHg and/or diastolic blood pressure \<50 mmHg).
• Known significant mental illness or other condition, such as active alcohol or other substance abuse or addiction, that in the opinion of the investigator predisposes the participant to high risk of noncompliance with the protocol.
• In participants with AML/MDS, rapidly progressive or highly proliferative disease or other criteria that render the participant at high risk of requiring intensive cytotoxic chemotherapy within the next 3 months.

Sponsors & Collaborators

• Taiho Oncology, Inc.: lead

Study Sites (22)

MD Anderson

Houston, Texas, 77030, United States

RECRUITING

Erebuni Medical Center

Yerevan, Armenia

RECRUITING

Hematology Center After Prof. R. Yeolyan (Adult Blood Disorders)

Yerevan, Armenia

RECRUITING

Hematology Center After Prof. R. Yeolyan (Clinic of Adults Oncology)

Yerevan, Armenia

RECRUITING

National Center of Oncology Named After V.A. Fanarjyan

Yerevan, Armenia

RECRUITING

Complex Oncology Center - Plovdiv - Base II

Plovdiv, Bulgaria

WITHDRAWN

BIO1

Vilnius, Lithuania

WITHDRAWN

Centrum Badań Klinicznych Piotr Napora Lekarze Sp. p.

Wroclaw, 51-162, Poland

RECRUITING

Institutul Oncologic Bucuresti - Prof. Dr. Alexandru Trestioreanu

Bucharest, 22328, Romania

RECRUITING

Institutul Oncologic Prof. Dr. Ion Chiricuta

Cluj-Napoca, 400015, Romania

RECRUITING

Summit Clinical Research s.r.o

Bratislava, 831 01, Slovakia

RECRUITING

START Barcelona - Hospital HM Nou Delfos

Barcelona, 8023, Spain

RECRUITING

Hospital Universitari Dexeus - Grupo Quirónsalud

Barcelona, Spain

WITHDRAWN

START Rioja - Hospital de San Pedro

La Rioja, 26006, Spain

NOT YET RECRUITING

Hospital Universitari Arnau de Vilanova

Lleida, Spain

RECRUITING

START Madrid - Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, 28046, Spain

RECRUITING

START Madrid - CIOCC - HM Sanchinarro

Madrid, 28050, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, Spain

WITHDRAWN

Hospital Clínico Universitario Virgen de la Arrixaca (Hematology Dept)

Murcia, 30120, Spain

RECRUITING

Hospital Clínico Universitario Virgen de la Arrixaca (Solid Tumor Dept)

Murcia, Spain

RECRUITING

Hospital Universitari i Politècnic La Fe

Valencia, Spain

TERMINATED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

decitabine and cedazuridine drug combination

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Central Study Contacts

Taiho Oncology, Inc.

CONTACT

+1 844-878-2446; medicalinformation@taihooncology.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2021
• First Posted: July 8, 2021
• Study Start: December 23, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

LI (1); AR (4); PL (1); BU (1); SL (1); ES (11); RO (2); US (1)