ASTX727 in Recurrent/Progressive Non-enhancing IDH Mutant Gliomas

  • STATUS
    Recruiting
  • End date
    May 31, 2024
  • participants needed
    18
  • sponsor
    Massachusetts General Hospital
Updated on 25 January 2021

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.

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.

Details
Condition CNS Malignancy, Neurological Cancer, malignant central nervous system tumor, central nervous system cancer
Treatment ASTX727
Clinical Study IdentifierNCT03922555
SponsorMassachusetts General Hospital
Last Modified on25 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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
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

Exclusion Criteria

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 >38.5C 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
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
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