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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04872543
Recruitment Status : Recruiting
First Posted : May 4, 2021
Last Update Posted : June 18, 2021
Sponsor:
Collaborator:
Astex Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Malignant Peripheral Nerve Sheath Tumors (MPNST) Drug: ASTX727 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This is a phase II trial to evaluate the efficacy of ASTX727 in patients with PRC2-loss MPNST.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of ASTX727 in Patients With PRC2 Loss Malignant Peripheral Nerve Sheath Tumor (MPNST)
Actual Study Start Date : April 29, 2021
Estimated Primary Completion Date : April 2026
Estimated Study Completion Date : April 2026


Arm Intervention/treatment
Experimental: ASTX727 (cedazuridine and decitabine)
Patients who meet the eligibility criteria will be treated with oral ASTX727 (INQOVI) on days 1-5 of each 28-day cycle. 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: ASTX727
ASTX727 will be self-administered orally by the patient on a once daily basis, days 1 through 5 of each 28-day cycle. Cycle 1 day 1 (C1D1) is defined as the first day that ASTX727 is administered.




Primary Outcome Measures :
  1. the best clinical benefit rate (CBR) [ Time Frame: at the end of 16 weeks ]
    (complete response [CR] + partial response [PR] + stable disease [SD]) by RECIST1.1


Secondary Outcome Measures :
  1. objective response rate (ORR) [ Time Frame: 8 weeks ]
    by RECIST1.1



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 18 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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04872543


Contacts
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Contact: Ping Chi, MD, PhD 646-888-4166 zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org
Contact: Ciara Kelly, MBBCH BAO 646-888-4312 zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org

Locations
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United States, New Jersey
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities) Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Ping Chi, MD, PhD    646-888-4166    zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org   
Memorial Sloan Kettering Monmouth (Limited Protocol Activities) Recruiting
Middletown, New Jersey, United States, 07748
Contact: Ping Chi, MD, PhD    646-888-4166    zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org   
Memorial Sloan Kettering Bergen (Limited Protocol Activities) Recruiting
Montvale, New Jersey, United States, 07645
Contact: Ping Chi, MD, PhD    646-888-4166    zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org   
United States, New York
Memorial Sloan Kettering Commack (Limited Protocol Activities) Recruiting
Commack, New York, United States, 11725
Contact: Ping Chi, MD, PhD    646-888-4166    zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org   
Memorial Sloan Kettering Westchester (Limited Protocol Activities) Recruiting
Harrison, New York, United States, 10604
Contact: Ping Chi, MD, PhD    646-888-4166    zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org   
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Ping Chi, MD, PhD    646-888-4166    zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org   
Contact: Ciara Kelly, MBBCH BAO    646-888-4312      
Memorial Sloan Kettering Nassau (Limited Protocol Activities) Recruiting
Uniondale, New York, United States, 11553
Contact: Ping Chi, MD, PhD    646-888-4166    zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org   
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Astex Pharmaceuticals, Inc.
Investigators
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Principal Investigator: Ping Chi, MD, PhD Memorial Sloan Kettering Cancer Center
Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT04872543    
Other Study ID Numbers: 21-048
First Posted: May 4, 2021    Key Record Dates
Last Update Posted: June 18, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Memorial Sloan Kettering Cancer Center:
ASTX727
Cedazuridine
Decitabine
PRC2 mutation
21-048
Additional relevant MeSH terms:
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Nerve Sheath Neoplasms
Neurofibrosarcoma
Neoplasms, Nerve Tissue
Neoplasms by Histologic Type
Neoplasms
Peripheral Nervous System Neoplasms
Nervous System Neoplasms
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Fibrosarcoma
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Sarcoma
Neurofibroma