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AzTrials

Acute Myeloid LeukemiaPhase 1NCT04953910

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

A Phase 1 study testing ASTX727 in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by Taiho Oncology, Inc. at 22 sites in 8 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
ASTX727
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
22 sitesin 8 countries
Study dates
23 Dec 2022to Dec 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • or
  • AML or MDS. or
  • A hematologic malignancy other than AML or MDS for which standard life-prolonging measures are not available.
Show all 26Show fewer
  • 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:
  • Normal hepatic function (Group A): total bilirubin ≤1× ULN; aspartate aminotransferase (AST): ≤1× ULN;
  • Moderate hepatic impairment (Group B): total bilirubin >1.5 to 3 × ULN; AST: any value;
  • Severe hepatic impairment (Group C): total bilirubin >3 × ULN; AST: any value.
  • Adequate renal function defined as creatinine clearance (CLcr, >50 mL/min according to the Cockcroft-Gault equation):
  • CLcr (mL/min) = [(140-age(years)] × weight (in kg)/ 72 × serum creatinine (in mg/dL)) × 0.85 [if female]
  • No major surgery within 30 days of first administration of oral decitabine and cedazuridine.
  • Life expectancy of at least 3 months.
  • Women of childbearing potential (according to recommendations of the Clinical Trial Facilitation Group) must not be pregnant or breastfeeding and must have a negative pregnancy test at screening.
  • Women of childbearing potential must agree to practice 1 highly effective contraceptive measure of birth control with low user dependency and must agree not to become pregnant for 6months after completing treatment
  • Male participants with female partners of childbearing potential must agree to use a male condom and advise his partner to practice 1 highly effective contraceptive measure of birth control (user dependent or with low user dependency) and must agree not to father a child while receiving treatment with oral decitabine and cedazuridine and for at least 3 months after completing treatment.

Who cannot join

  • 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.
Show all 26Show fewer
  • 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.
  • or
  • History or disposition for torsades des pointes (TdP) (e.g., heart failure, hypokalemia, family history of long QT Syndrome).
  • or
  • 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).
  • or
  • 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.
  • Life-threatening illness or severe organ system dysfunction, such as uncontrolled congestive heart failure or chronic obstructive pulmonary disease, or other reasons including laboratory abnormalities, that, in the investigator's opinion, could compromise the participant's safety, interfere with the absorption or metabolism of oral decitabine and cedazuridine, or compromise completion of the study or integrity of the study outcomes.
  • Untreated central nervous system (CNS) metastases. Participants with treated CNS metastases are eligible provided they have been clinically stable for at least 4 weeks before screening.
  • Participants infected with human immunodeficiency virus (HIV).
  • Positive blood screen for hepatitis C antibody (HCV+) and positive RNA polymerase chain reaction (PCR). Participant can be included if HCV+ but negative for RNA PCR.
  • Positive blood screen for hepatitis B surface antigen (HBsAg+). Participants with positive blood screen for hepatitis B surface antibody (HBsAb+) and negative hepatitis B core antibody (HBcAb-) can be included if negative for hepatitis B surface antigen (HBsAg-).
  • Average intake of more than 24 units of alcohol per week for male participants and 17 units per week for female participant (1 unit of alcohol equals 10 mL of pure alcohol, i.e., approximately 250 mL of beer, 75 mL of wine, or 25 mL of spirits).
  • Donation or loss of more than 500 mL of blood within 60 days prior to the first study drug administration.
  • Hypersensitivity to decitabine, cedazuridine, or any of the excipients in oral decitabine and cedazuridine.

Trial locations and contacts

22 sites in 8 countries. Contact the study team or a site near you to ask about taking part.

Taiho Oncology, Inc. contact

+1 844-878-2446

medicalinformation@taihooncology.com

22 sites in 8 countries

Spain11 sites, 8 recruiting

  • START Barcelona - Hospital HM Nou Delfos

    Barcelona, 8023

    Recruiting

  • Hospital Universitari Dexeus - Grupo Quirónsalud

    Barcelona

    Withdrawn

  • START Rioja - Hospital de San Pedro

    La Rioja, 26006

    Recruiting

  • Hospital Universitari Arnau de Vilanova

    Lleida

    Recruiting

  • START Madrid - Hospital Universitario Fundación Jiménez Díaz

    Madrid, 28040

    Recruiting

  • Hospital Universitario La Paz

    Madrid, 28046

    Recruiting

  • START Madrid - CIOCC - HM Sanchinarro

    Madrid, 28050

    Recruiting

  • Hospital Universitario 12 de Octubre

    Madrid

    Withdrawn

  • Hospital Clínico Universitario Virgen de la Arrixaca (Hematology Dept)

    Murcia, 30120

    Recruiting

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

    Murcia

    Recruiting

  • Hospital Universitari i Politècnic La Fe

    Valencia

    Terminated

Other trials in Spain

Armenia4 sites, 4 recruiting

  • Erebuni Medical Center

    Yerevan

    Recruiting

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

    Yerevan

    Recruiting

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

    Yerevan

    Recruiting

  • National Center of Oncology Named After V.A. Fanarjyan

    Yerevan

    Recruiting

Other trials in Armenia

Romania2 sites, 2 recruiting

  • Institutul Oncologic Bucuresti - Prof. Dr. Alexandru Trestioreanu

    Bucharest, 22328

    Recruiting

  • Institutul Oncologic Prof. Dr. Ion Chiricuta

    Cluj-Napoca, 400015

    Recruiting

Other trials in Romania

United States1 site, 1 recruiting

  • MD Anderson

    Houston, Texas, 77030

    Recruiting

Other trials in United States

Bulgaria1 site

  • Complex Oncology Center - Plovdiv - Base II

    Plovdiv

    Withdrawn

Other trials in Bulgaria

Lithuania1 site

  • BIO1

    Vilnius

    Withdrawn

Other trials in Lithuania

Poland1 site, 1 recruiting

  • Centrum Badań Klinicznych Piotr Napora Lekarze Sp. p.

    Wroclaw, 51-162

    Recruiting

Other trials in Poland

Slovakia1 site, 1 recruiting

  • Summit Clinical Research s.r.o

    Bratislava, 831 01

    Principal Investigator

    Recruiting

Other trials in Slovakia

About this study

Official title: A Phase 1b, Open-label, Parallel Group, Multiple-dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Oral Decitabine and Cedazuridine (ASTX727) in Cancer Patients With Moderate and Severe Hepatic Impairment

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.

Being tested
ASTX727
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ASTX727Drug

    Also called Oral decitabine and cedazuridine

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

Study groups in NCT04953910
Study groupRoleWhat they receive
Group B: Moderate hepatic impairmentExperimentalCancer participants with moderate hepatic impairment [total bilirubin >1.5X - 3X upper limit of normal (ULN); any aspartate aminotransferase (AST) level]
Receives: Drug: ASTX727
Group C: Severe hepatic impairmentExperimentalCancer participants with severe hepatic impairment (>3X ULN; any AST level)
Receives: Drug: ASTX727
Group A: Normal hepatic functionActive comparatorCancer participants with normal hepatic function (total bilirubin ≤ULN; AST ≤ULN)
Receives: Drug: ASTX727

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (15)

  1. Pharmacokinetic Parameter: Apparent Clearance (CL/F)

    CL/F of decitabine and cedazuridine.

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

  2. Pharmacokinetic Parameter: Renal Clearance (CLR)

    CLR of decitabine, cedazuridine, and cedazuridine-epimer.

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

  3. Pharmacokinetic Parameter: Apparent Nonrenal Clearance (CLNR/F)

    CLNR/F of decitabine and cedazuridine.

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

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

    Tmax of decitabine, cedazuridine, and cedazuridine-epimer.

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

  5. Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax)

    Cmax of decitabine, cedazuridine, and cedazuridine-epimer.

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

  6. Pharmacokinetic Parameter: Plasma Concentration Prior to Dosing (Ctrough)

    Ctrough of decitabine, cedazuridine, and cedazuridine-epimer.

    Measured: Predose on Days 2, 3, 4, and 5

  7. Pharmacokinetic Parameter: Area Under the Concentration-time Curve from Time 0 (Time of Dosing) to Time t (AUCt)

    AUCt of decitabine, cedazuridine, and cedazuridine-epimer, where t is the last time point with concentrations above the lower limit of quantitation.

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

  8. Pharmacokinetic Parameter: Pharmacokinetic Parameter: AUC Within 1 Dosing Interval (AUCtau)

    AUCtau of decitabine, cedazuridine, and cedazuridine-epimer.

    Measured: Predose from Day 1 to Day 2, Day 2 to Day 3, and Day 5 to Day 6 and at multiple timepoints on Day 1 to Day 2, Day 2 to Day 3, and Day 5 to Day 6

  9. Pharmacokinetic Parameter: AUC From Time 0 Extrapolated to Infinity (AUC0-inf)

    AUC0-inf of decitabine, cedazuridine, and cedazuridine-epimer.

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

  10. Pharmacokinetic Parameter: Terminal Elimination Phase Rate Constant (λz)

    λz of decitabine, cedazuridine, and cedazuridine-epimer.

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

  11. Pharmacokinetic Parameter: Terminal Elimination Half-life (t1/2)

    t1/2 of decitabine, cedazuridine, and cedazuridine-epimer.

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

  12. Pharmacokinetic Parameter: Apparent Volume of Distribution During Terminal Phase (Vz/F)

    Vz/F of decitabine and cedazuridine.

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

  13. Pharmacokinetic Parameter: Fraction of Administered Drug Excreted into Urine (Fe/F))

    Fe/F of decitabine and cedazuridine.

    Measured: Predose and at multiple timepoints post-dose up to 24 hours

  14. Pharmacokinetic Parameter: Cumulative Amount Excreted from Time 0 to the Time of the Last Quantifiable Sample (Aelast)

    Aelast of decitabine, cedazuridine, and cedazuridine-epimer.

    Measured: Predose and at multiple timepoints post-dose up to 24 hours

  15. Safety Parameter: Number of Participants with Adverse Events (AEs)

    Adverse events included any untoward medical occurrence in a participant administered a drug; it does not necessarily have to have a causal relationship with this treatment also including clinically meaningful findings in laboratory safety tests, vital signs, physical examinations, and electrocardiogram (ECG) findings.

    Measured: Up to 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jul 2021
  2. Study start23 Dec 2022
  3. Primary completionDec 2026 (estimated)
  4. Study completionDec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
27 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04953910
Sponsor's protocol ID
ASTX727-18
Other IDs
2024-516292-33-00
Status last verified
May 2026
First submitted
30 Jun 2021
Last updated
28 May 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ASTX727 in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by Taiho Oncology, Inc. at 22 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 28 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in Spain, Armenia, Romania, United States, Bulgaria and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Taiho Oncology, Inc. (+1 844-878-2446, medicalinformation@taihooncology.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetic Parameter: 5-day Cumulative Area Under the Concentration-time Curve Within 1 Dosing Interval (AUCtau) (time frame: Predose and at multiple timepoints post-dose from Day 1 to Day 5). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04953910.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2026.

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