ASTX727 in Recurrent/Progressive Non-enhancing IDH Mutant Gliomas

NCT03922555 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 18-631
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Neurological Cancer

Keywords

Neurological Cancer

Outcome Measures

Primary Outcomes (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.

  1 year

Secondary Outcomes (3)

• Median Progression Free Survival

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

• Overall Survival

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

• Response Rate

  1 Year

Study Arms (2)

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.

Drug: ASTX727

Expansion Cohort

EXPERIMENTAL

* 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

Drug: ASTX727

Interventions

ASTX727 DRUG

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.

ASTX727 (Cedazuridine + Cytidine Antimetabolite Decitabine); Expansion Cohort

Eligibility Criteria

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

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Astex Pharmaceuticals, Inc.: collaborator

Study Sites (3)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

MeSH Terms

Conditions

Central Nervous System Neoplasms

Interventions

decitabine and cedazuridine drug combination

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases

Study Officials

• Isabel Arrillaga-Romany

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Isabel Arrillaga-Romany, MD

CONTACT

617-724-4000; iarrillaga@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 17, 2019
• First Posted: April 22, 2019
• Study Start: July 12, 2019
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): August 1, 2028
• Last Updated: April 16, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: BCH - Contact the Technology \& Innovation Development Office at www.childrensinnovations.org or email TIDO@childrens.harvard.edu BIDMC - Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu BWH - Contact the Partners Innovations team at http://www.partners.org/innovation DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu MGH - Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (3)