- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04872543
A Study of ASTX727 in People With Malignant Peripheral Nerve Sheath Tumors (MPNST)
A Phase II Study of ASTX727 in Patients With PRC2 Loss Malignant Peripheral Nerve Sheath Tumor (MPNST)
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.
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Ciara Kelly, MBBCH BAO
- Phone Number: 646-888-4312
- Email: zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org
Study Contact Backup
- Name: Ping Chi, MD, PhD
- Phone Number: 646-888-4166
- Email: zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org
Study Locations
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New Jersey
-
Basking Ridge, New Jersey, United States, 07920
- Recruiting
- Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
-
Contact:
- Ping Chi, MD, PhD
- Phone Number: 646-888-4166
- Email: zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org
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Middletown, New Jersey, United States, 07748
- Recruiting
- Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
-
Contact:
- Ping Chi, MD, PhD
- Phone Number: 646-888-4166
- Email: zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org
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Montvale, New Jersey, United States, 07645
- Recruiting
- Memorial Sloan Kettering Bergen (Limited Protocol Activities)
-
Contact:
- Ping Chi, MD, PhD
- Phone Number: 646-888-4166
- Email: zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org
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New York
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Commack, New York, United States, 11725
- Recruiting
- Memorial Sloan Kettering Commack (Limited Protocol Activities)
-
Contact:
- Ping Chi, MD, PhD
- Phone Number: 646-888-4166
- Email: zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org
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Harrison, New York, United States, 10604
- Recruiting
- Memorial Sloan Kettering Westchester (Limited Protocol Activities)
-
Contact:
- Ping Chi, MD, PhD
- Phone Number: 646-888-4166
- Email: zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org
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New York, New York, United States, 10065
- Recruiting
- Memorial Sloan Kettering Cancer Center
-
Contact:
- Ping Chi, MD, PhD
- Phone Number: 646-888-4166
- Email: zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org
-
Contact:
- Ciara Kelly, MBBCH BAO
- Phone Number: 646-888-4312
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Uniondale, New York, United States, 11553
- Recruiting
- Memorial Sloan Kettering Nassau (Limited Protocol Activities)
-
Contact:
- Ping Chi, MD, PhD
- Phone Number: 646-888-4166
- Email: zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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 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.
|
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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
at the end of 16 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
objective response rate (ORR)
Time Frame: 8 weeks
|
by RECIST1.1
|
8 weeks
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Ping Chi, MD, PhD, Memorial Sloan Kettering Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Nervous System Diseases
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Neuromuscular Diseases
- Neoplasms, Nerve Tissue
- Peripheral Nervous System Diseases
- Nervous System Neoplasms
- Neoplasms, Connective Tissue
- Sarcoma
- Peripheral Nervous System Neoplasms
- Neoplasms, Fibrous Tissue
- Fibrosarcoma
- Neurofibroma
- Nerve Sheath Neoplasms
- Neurofibrosarcoma
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Decitabine and cedazuridine drug combination
Other Study ID Numbers
- 21-048
- 1R01FD007544-01 (U.S. FDA Grant/Contract)
- Philanthropy (Other Identifier: Philanthropy)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Malignant Peripheral Nerve Sheath Tumors (MPNST)
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Oslo University HospitalMerck Sharp & Dohme LLCTerminatedMalignant Peripheral Nerve Sheath Tumour (MPNST)Norway
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Sarcoma Alliance for Research through CollaborationUnited States Department of Defense; Synta Pharmaceuticals Corp.CompletedSarcoma | Malignant Peripheral Nerve Sheath Tumors (MPNST)United States
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National Cancer Institute (NCI)Active, not recruitingAdvanced Malignant Solid Neoplasm | Unresectable Malignant Solid Neoplasm | Metastatic Malignant Solid Neoplasm | NF1 Mutation Positive Malignant Peripheral Nerve Sheath TumorUnited States
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Ascentage Pharma Group Inc.Merck Sharp & Dohme LLCRecruitingMelanoma | P53 Mutation | Uveal Melanoma | Cutaneous Melanoma | Mucosal Melanoma | Malignant Peripheral Nerve Sheath Tumors | MPNST | Unresectable or Metastatic Melanoma or Advanced Solid Tumors | MDM2 Gene MutationUnited States, Australia
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National Cancer Institute (NCI)CompletedNeurofibromatosis | MPNSTUnited States
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Memorial Sloan Kettering Cancer CenterWashington University School of Medicine; University of California, Los Angeles and other collaboratorsTerminatedSarcoma | Leiomyosarcoma | Malignant Peripheral Nerve Sheath Tumor | Malignant Fibrous | Histiocytoma/Undifferentiated Pleomorphic SarcomaUnited States
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University Health Network, TorontoActive, not recruitingSoft Tissue Sarcoma | Leiomyosarcoma | Endometrial Stromal Sarcoma | Malignant Peripheral Nerve Sheath Tumor (MPNST)Canada
Clinical Trials on ASTX727
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Astex Pharmaceuticals, Inc.CompletedMyelodysplastic Syndrome | MDSUnited States, Canada
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M.D. Anderson Cancer CenterGenentech, Inc.; Astex Pharmaceuticals, Inc.RecruitingChronic Myelomonocytic Leukemia | Myelodysplastic SyndromeUnited States
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M.D. Anderson Cancer CenterRecruitingAcute Myeloid Leukemia | Recurrent Acute Myeloid Leukemia | Refractory Acute Myeloid LeukemiaUnited States
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M.D. Anderson Cancer CenterActive, not recruitingRecurrent Acute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Recurrent Acute Biphenotypic Leukemia | Refractory Acute Biphenotypic LeukemiaUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI); Astex Pharmaceuticals, Inc.RecruitingChronic Phase Chronic Myelogenous Leukemia | Philadelphia Chromosome Positive | BCR-ABL1 Positive Chronic Myelogenous Leukemia | BCR-ABL1 PositiveUnited States
-
Astex Pharmaceuticals, Inc.CompletedAcute Myeloid Leukemia | Myelodysplastic Syndromes | Chronic Myelomonocytic LeukemiaUnited States
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Astex Pharmaceuticals, Inc.Active, not recruitingMyelodysplastic SyndromesSpain, United States, Belgium, Canada, Germany, Italy
-
M.D. Anderson Cancer CenterRecruitingAcute Myeloid Leukemia | Myelodysplastic Syndrome | Recurrent Acute Myeloid Leukemia | Refractory Acute Myeloid LeukemiaUnited States
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Vanderbilt-Ingram Cancer CenterAstex Pharmaceuticals, Inc.; Forma Therapeutics, Inc.WithdrawnAcute Myeloid Leukemia | Myelodysplastic Syndrome | Recurrent Acute Myeloid Leukemia | Recurrent Myelodysplastic Syndrome | Refractory Acute Myeloid Leukemia | Refractory Myelodysplastic Syndrome