A Study of ASTX727 in People With Malignant Peripheral Nerve Sheath Tumors (MPNST)

NCT ID: NCT04872543

Last Updated: 2025-12-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-04-29

Study Completion Date

2026-04-30

Brief Summary

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The purpose of this study is to see whether the study drug ASTX727 is an effective treatment for people who have MPNST with a PCR2 mutation.

ASTX727 is a combination of two drugs (cedazuridine and decitabine) that have been designed to target cancer cells with a PCR2 mutation and to disrupt the cells' ability to survive and grow. The study researchers think that the study drug allows decitabine to work better than decitabine given alone.

Detailed Description

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Conditions

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Malignant Peripheral Nerve Sheath Tumors (MPNST)

Keywords

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ASTX727 Cedazuridine Decitabine PRC2 mutation 21-048

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

This is a phase II trial to evaluate the efficacy of ASTX727 in patients with PRC2-loss MPNST.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ASTX727 (cedazuridine and decitabine)

Patients who meet the eligibility criteria will be treated with oral ASTX727 (INQOVI) on days 1-5 of each 21-day cycle with Pegfilgrastim support on day 7. A delay in the start of subsequent cycles due to holidays, weather, or other circumstances will be permitted up to 7 days and not considered a protocol deviation. Drug dosing will be interrupted for any Grade 4 adverse events or clinically significant laboratory abnormalities. For Grade 3 or 4 AE, if the AE returns to Grade 1 or baseline, the patient may be re-escalated.

Group Type EXPERIMENTAL

ASTX727

Intervention Type DRUG

ASTX727 will be self-administered orally by the patient on a once daily basis, days 1 through 5 of each 21-day cycle. Cycle 1 day 1 (C1D1) is defined as the first day that ASTX727 is administered.

Interventions

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ASTX727

ASTX727 will be self-administered orally by the patient on a once daily basis, days 1 through 5 of each 21-day cycle. Cycle 1 day 1 (C1D1) is defined as the first day that ASTX727 is administered.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patients must have pathologically confirmed PRC2 loss MPNSTs (e.g. IHC of loss H3K27me2 and/or H3K27me3 immunostaining, and/or inactivating mutations in EED, SUZ12, EZH2 by CLIA approved genetic assays), which are advanced, unresectable or metastatic and have progressed on at least one line of standard of care systemic therapy, or administration of cytotoxic chemotherapy is not considered in the best interest for the patient.
* Patients must be at least 16 years of age
* Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
* Disease must be measurable by RECIST 1.1.
* Patients must be able to take oral medications.
* Patient or legally authorized representative can understand and comply with the protocol and must sign an informed consent document.
* Adequate renal, hepatic and hematologic function as the following: serum creatinine ≤ 1.5 x upper limit of normal (ULN), total serum bilirubin ≤ 1.5 x ULN, serum AST (SGOT) ≤ 2.5 x ULN (or ≤ 5.0 x ULN if considered due to tumor (liver metastases)), serum ALT (SGPT) ≤ 2.5 x ULN (or ≤ 5.0 x ULN if considered due to tumor (liver metastases)), ANC ≥ 1500/µL, platelets ≥ 75,000/µL, and hemoglobin ≥ 9 g/dL(can be transfused to achieve this). Prothrombin time (PT), international normalized ratio (INR), and partial thromboplastin time \> 1.5 x ULN. Patients on a stable maintenance regimen of anticoagulation therapy for at least 30 days prior to screening may have PT/INR measurements \> 1.5 x ULN
* Patients of childbearing potential must have a negative serum pregnancy test at screening and at cycle 1 day 1 (-3 days) prior to the first dose of study therapy being administered. Female patients of childbearing potential must agree to use two reliable methods of contraception starting at signing the ICF, during and for 6 months following the last dose of study drug
* Women must agree not to breastfeed during treatment with study drug and for 2 weeks after the last dose.
* Sexually active males must agree to use a condom during intercourse and agree to not donate sperm while taking the drug and for 3 months after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men to prevent delivery of the drug via seminal fluid.

Exclusion Criteria

* Patients have a severe and/or uncontrolled medical disease (e.g., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection).
* Patients have known active brain metastasis or leptomeningeal disease.
* Active or chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) or known active or chronic infection with human immunodeficiency virus (HIV). Prior hepatitis infection that has been treated with highly effective therapy with no evidence of residual infection (including undetectable viral loads while on antiviral therapy) and with normal liver function (ALT, AST, total and direct bilirubin ≤ ULN) is allowed.
* Known active tuberculosis.
* Concurrent active inoperable locally advanced or metastatic malignancy (except for malignancies which the treating investigator determines are unlikely to interfere with treatment and safety analysis or are less of a treatment priority than their diagnosis of advanced MPNST).
* Patients have clinically significant cardiovascular disease, including any of the following: 1) History of acute coronary syndrome including myocardial infarction, unstable angina, CABG, coronary angioplasty or stenting \< 6 months prior to screening; 2) symptomatic chronic heart failure (New York Heart Association Criteria, Class II-IV); 3) evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities \< 6 months prior to screening except atrial fibrillation (AF) and paroxysmal supraventricular tachycardia (PSVT).
* A screening Fridericia corrected QT interval (QTcF) ≥ 450 ms (men) or ≥ 470 ms (women) (average of triplicates).
* Left ventricular ejection fraction (LVEF) \<50% as determined by a multigated acquisition (MUGA) scan or echocardiogram.
* History of thromboembolic or cerebrovascular events ≤ 3 months prior to starting study treatment, including transient ischemic attacks, cerebrovascular accidents, deep vein thrombosis or pulmonary emboli.
* Impairment of gastrointestinal function or gastrointestinal disease (e.g., uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, ulcerative diseases, bowel resection with decreased intestinal absorption).
* Patients had a major surgery within 3 weeks prior to study entry or who have not recovered from side effects of such procedure.
* Patients with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
* Treatment with anti-cancer therapy within 14 days prior to the first dose of study drug therapy. For prior biological therapies, e.g., monoclonal antibodies with a half-life longer than 3 days, the interval must be at least 28 days prior to the first dose of study drug.
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Taiho Pharmaceuticals, Inc.

UNKNOWN

Sponsor Role collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ping Chi, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

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Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, United States

Site Status RECRUITING

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, United States

Site Status RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, United States

Site Status RECRUITING

Memorial Sloan Kettering Commack (Limited Protocol Activities)

Commack, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Ping Chi, MD, PhD

Role: CONTACT

Phone: 646-888-4166

Email: [email protected]

Ciara Kelly, MBBCH BAO

Role: CONTACT

Phone: 646-888-4312

Email: [email protected]

Facility Contacts

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Ping Chi, MD, PhD

Role: primary

Ping Chi, MD, PhD

Role: primary

Ping Chi, MD, PhD

Role: primary

Ping Chi, MD, PhD

Role: primary

Ping Chi, MD, PhD

Role: primary

Ping Chi, MD, PhD

Role: primary

Ciara Kelly, MBBCH BAO

Role: backup

Ping Chi, MD, PhD

Role: primary

Related Links

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http://www.mskcc.org/mskcc/html/44.cfm

Memorial Sloan Kettering Cancer Center

Other Identifiers

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1R01FD007544-01

Identifier Type: FDA

Identifier Source: secondary_id

View Link

Philanthropy

Identifier Type: OTHER

Identifier Source: secondary_id

21-048

Identifier Type: -

Identifier Source: org_study_id