RECRUITING

ASTX727 in Recurrent/Progressive Non-enhancing IDH Mutant Gliomas

Conditions

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

this research study is evaluating the highest dose of ASTX727 that can be administered safely to recurrent/progressive non-enhancing IDH mutant gliomas patients.

Official Title

Phase I Trial of ASTX727 in Recurrent/Progressive Non-enhancing IDH Mutant Gliomas

Quick Facts

Study Start:2019-07-12

Study Completion:2025-05-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03922555

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	* 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. * 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

Inclusion Criteria

Exclusion 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.

* 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.
* 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

Contacts and Locations

Study Contact

Isabel Arrillaga-Romany, MD

CONTACT

617-724-4000

iarrillaga@mgh.harvard.edu

Principal Investigator

Isabel Arrillaga-Romany

PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Study Locations (Sites)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114

United States

Brigham and Women's Hospital

Boston, Massachusetts, 02115

United States

Dana Farber Cancer Institute

Boston, Massachusetts, 02115

United States

Collaborators and Investigators

Sponsor: Massachusetts General Hospital

Isabel Arrillaga-Romany, PRINCIPAL_INVESTIGATOR, Massachusetts General Hospital

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2019-07-12

Study Completion Date2025-05-31

Study Record Updates

Study Start Date2019-07-12

Study Completion Date2025-05-31

Terms related to this study

Keywords Provided by Researchers

Neurological Cancer

Additional Relevant MeSH Terms

Neurological Cancer