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Neurological CancerPhase 1NCT03922555

ASTX727 in Recurrent/Progressive Non-enhancing IDH Mutant Gliomas

A Phase 1 study testing ASTX727 in people with Neurological Cancer, run by Massachusetts General Hospital at 3 sites in United States.

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 research study is evaluating the highest dose of ASTX727 that can be administered safely to recurrent/progressive non-enhancing IDH mutant gliomas patients. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neurological Cancer
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
18 participants
Where
3 sitesUnited States
Study dates
12 Jul 2019to 1 Aug 2028
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

  • Participants must be ≥18 years of age.
  • Participants must have histologically or cytologically confirmed glioma, with documented IDH1 and/or IDH2 gene-mutation.
  • Participants must have radiographic evidence of non-enhancing disease progression/recurrence per RANO criteria for low grade gliomas (LGG).
  • Patients who have received prior treatment with chemotherapy, radiation, or a combination of both are eligible. Also, patients who have not received any prior treatment for their glioma are also eligible.
  • Participants must be ≥12 weeks from completion of radiation.
  • Participants must have a baseline brain MRI scan within 28 days prior to Day 1 of treatment.
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  • Participants must be on a stable or decreasing dose of glucocorticoids for 7 days prior to registration.
  • Participants must have archived primary tumor biopsies or surgical specimens for additional exploratory translational studies. At least 100-micron length of FFPE tissue or a tissue block should be available for enrollment and for shipment to the Sponsor, or a laboratory designated by the Principal Investigator. If less material is available, participants could still be eligible after discussion with the Principal Investigator who will assess and confirm that there is sufficient material for key evaluations.
  • Participants must be able to understand and willing to sign an informed consent. A legally authorized representative may consent on behalf of a participant who is otherwise unable to provide informed consent, if acceptable to and approved by the site and/or site's Institutional Review Board (IRB)/Independent Ethics Committee (IEC).
  • Participants must have KPS ≥ to 70
  • Participants must have expected survival of ≥ 6 months.
  • Participants must have adequate bone marrow function as evidenced by:
  • Leukocytes ≥ 3,000/mcL
  • Absolute neutrophil count ≥1500/mcL;
  • Hemoglobin ≥10 g/dL
  • Platelets ≥100,000/mcL
  • Participants must have adequate hepatic function as evidenced by:
  • Serum total bilirubin ≤1.5 x upper limit of normal (ULN), unless considered due to Gilbert's disease
  • Aspartate aminotransferase (AST), Alanine Aminotransferase (ALT), and alkaline phosphatase (ALP) ≤3.0 x ULN.
  • Participants must have adequate renal function as evidenced by:
  • Serum creatinine ≤2.0 x ULN
  • OR Creatinine clearance >40 mL/min based on the Cockroft-Gault glomerular filtration rate (GFR) estimation: (140 - Age) × (weight in kg) × (0.85 if female)/72 × serum creatinine
  • Participants must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of cancer. (Participants with residual Grade 1 toxicity due to prior chemotherapy are allowed).
  • Female participants with reproductive potential must have a negative serum pregnancy test within 14 days prior to the first study drug administration. Participants with reproductive potential are defined as sexually mature women who have not undergone a hysterectomy, bilateral oophorectomy or tubal occlusion or who have not been naturally postmenopausal (i.e., who have not menstruated at all) for at least 24 consecutive months (i.e., have had menses at any time in the preceding 24 consecutive months). Women with reproductive potential as well as fertile men and their partners who are female with reproductive potential must agree to abstain from sexual intercourse or to use 2 effective forms of contraception from the time of giving informed consent, during the study, and for 90 days (females and males) following the last dose of ASTX727.
  • Participants enrolling in the expansion cohort (Arm B) must meet all of the above criteria and must have surgically accessible tumors and be surgical candidates.

Who cannot join

  • Participants with enhancing disease on brain MRI.
  • Participants who received systemic anticancer therapy <28 days prior to registration. One exception: participants on lomustine/CCNU must wait at least 42 days from last date of drug administration to registration.
  • Participants who received an investigational agent <14 days prior to registration. In addition, the first dose of ASTX727 should not occur before a period ≥5 half-lives of the investigational agent has elapsed.
  • Participants with prior treatment with bevacizumab (Avastin) are excluded.
  • Participants who are pregnant or breast-feeding.
  • Participants with an active severe infection that requires anti-infective therapy or with an unexplained fever >38.5°C during screening visits or on their first day of study drug administration.
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  • Participants with known additional malignancy that is progressing or requires active treatment within 2 years of start of study drug. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer that has undergone potentially curative therapy, or surgically treated prostate cancer.
  • Participants with known hypersensitivity to any of the components of ASTX727.
  • Participants with a history of myocardial infarction within the 6 months prior to screening.
  • Participants with a known history of severe and/or uncontrolled ventricular arrhythmias.
  • Participants with QTc interval ≥450 msec or with other factors that significantly increase the risk of QT prolongation or arrhythmic events (e.g., family history of long QT interval syndrome).
  • Participants with known infection with human immunodeficiency virus (HIV) or active hepatitis B or C.
  • Participants with any other medical or psychological condition, deemed by the Investigator to be likely to interfere with a participant's ability to sign informed consent, cooperate, or participate in the study.
  • Participants with known dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally.
  • Participants with evidence of intracranial or intratumoral hemorrhage either by MRI or CT scan. Participants with resolving post-surgical changes, punctate/micro-hemorrhage, or hemosiderin are eligible.
  • Participants enrolling in the expansion cohort will be excluded is they are deemed by the treating physician or surgeon not to be suitable for surgery

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Isabel Arrillaga-Romany, MD contact

617-724-4000

iarrillaga@mgh.harvard.edu

United States3 sites, 3 recruiting

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

    Isabel Arrillaga-Romany, MD, 617-724-4000, iarrillaga@mgh.harvard.edu

    Isabel Arrillaga-Romany, MD

    Recruiting

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

    Ugonma Chukwueke, MD, Uchukwueke@partners.org

    Ugonma Chukwueke, MD

    Recruiting

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

    Ugonma Chukwueke, MD, Uchukwueke@partners.org

    Ugonma Chukwueke, MD

    Recruiting

Other trials in United States

About this study

Official title: Phase I Trial of ASTX727 in Recurrent/Progressive Non-enhancing IDH Mutant Gliomas

this research study is evaluating the highest dose of ASTX727 that can be administered safely to recurrent/progressive non-enhancing IDH mutant gliomas patients.

Read the detailed description

This research study is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drug is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved ASTX727 as a treatment for any disease.

ASTX727 is made up of the 2 study drugs cedazuridine and decitabine. Cedazuridine is believed to work by slowing down how fast decitabine is broken down by the body. Decitabine is believed to work by blocking abnormal cells or cancer cells from growing.

Being tested
ASTX727
Keywords
Neurological Cancer
Medical subject headings
Central Nervous System Neoplasms

What participants receive

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

  • ASTX727Drug

    ASTX727 is made up of the 2 study drugs cedazuridine and decitabine. Cedazuridine is believed to work by slowing down how fast decitabine is broken down by the body. Decitabine is believed to work by blocking abnormal cells or cancer cells from growing.

Study groups in NCT03922555
Study groupRoleWhat they receive
ASTX727 (Cedazuridine + Cytidine Antimetabolite Decitabine)Experimental-ASTX727 administered orally for 5 or 6 consecutive days every 28d cycle and will de-escalate to 4 consecutive days every 28 d cycle.
Receives: Drug: ASTX727
Expansion CohortExperimental* Oral ASTX727 will be administered daily for 4, 5 or 6 consecutive days * Surgical resection will take place 12 days (+/- 1 day) after initiation of treatment
Receives: Drug: ASTX727

What is being measured

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

  1. Maximum tolerated dose

    Participants will be enrolled at escalating doses using a standard 3+3 dose escalation design until the maximum administered dose is reached or until dose limiting toxicities result in the end of dose escalation. The maximum tolerated dose is the highest administered dose level at which participants experienced experienced 1 or fewer dose limiting toxicities.

    Measured: 1 year

Secondary outcomes (3)

  1. Median Progression Free Survival

    Progression-Free Survival (PFS) is defined as the time from randomization (or registration) to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation. Disease progression will be assessed using the Response Assessment in Neuro-Oncology (RANO) Working Group updated response assessment criteria for low-grade Gliomas.

    Measured: From the time of randomization until disease progression or death, up to five years

  2. Overall Survival

    Overall Survival (OS) is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive.

    Measured: From the time of randomization until death, up to five years

  3. Response Rate

    The number of participants achieving a complete or partial tumor response as assessed using the the Response Assessment in Neuro-Oncology (RANO) Working Group updated response assessment criteria for low-grade Gliomas.

    Measured: 1 Year

Timeline

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

  1. First posted22 Apr 2019
  2. Study start12 Jul 2019
  3. Primary completion1 Jan 2027 (estimated)
  4. Study completion1 Aug 2028 (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
Sequential
Masking
None (open label)
Enrolment
18 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03922555
Sponsor's protocol ID
18-631
Status last verified
Jul 2026
First submitted
17 Apr 2019
Last updated
24 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: Dr. Isabel Arrillaga-Romany. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ASTX727 in people with Neurological Cancer, run by Massachusetts General Hospital at 3 sites in United States.

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 25 inclusion and 16 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 24 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. 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 Isabel Arrillaga-Romany, MD (617-724-4000, iarrillaga@mgh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (time frame: 1 year). 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 NCT03922555.

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 24 Jul 2026.

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