Intermediate-size Expanded Access to ONC201 for Patients With H3 K27M-mutant and/or Midline Gliomas
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Layout table for eligibility information
Ages Eligible for Study:
0 Years and older (Child, Adult, Older Adult)
Sexes Eligible for Study:
Patient meets one or more of the criteria below:
Arm A - Closed to further enrollment
Arm B - Diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter and diffuse involvement of the pons. H3 K27M status does not have to be known or positive for this arm.
Patients with primary spinal glioma that is positive for the H3 K27M mutation (performed in a laboratory with Clinical Laboratory Improvement Amendments [CLIA] or equivalent certification). Primary spinal glioma must be documented in radiology reporting. OR
Patients with diffuse glioma that is positive for the H3 K27M mutation (performed in a laboratory with CLIA or equivalent certification) AND radiographic evidence of leptomeningeal disease. Leptomeningeal disease must be documented in radiology reporting.
Arm D Patients currently on-treatment with ONC201 in one of the following Chimerix studies: ONC006, ONC013, ONC014, ONC016, or ONC018 (referred to as "referring study"). Chimerix medical monitor (or designee) must provide written approval for each patient in this arm prior to enrollment.
Patient is not required to have radiographic or clinical evidence of progressive disease.
Arm C: Patient must have progressive disease as defined by Response Assessment in Neuro-Oncology (RANO) criteria or have documented recurrent glioma on diagnostic biopsy.
Arm D: Not applicable.
Arm B: Patient must be at least 14 days from completion of radiotherapy. Arm C: Patient must be at least 90 days from completion of radiotherapy. Arm D: Not applicable.
(Not applicable; criterion removed in Version 5).
Patient must weigh at least 10kg.
From the projected start of scheduled study treatment, the following time periods must have elapsed from prior anti-cancer treatments: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from anti-cancer antibodies (except 21 days forbevacizumab), 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies, and 1 week from devices used to treat cancer.
Arm D: Washouts are not applicable for Arm D patients as they are continuing treatment with ONC201 (and possibly other anticancer treatments as allowed per original referring study protocol).
Magnetic resonance imaging (MRI) of patient's glioma within 28 days prior to start of study drug.
Arm D: Additional MRI for eligibility is not required. Patient's most recent MRI as per referring protocol schedule will be acceptable.
Adequate organ and marrow function as defined below:
Absolute neutrophil count≥1,000/mm3 without growth factor use ≤7 days prior to treatment (Cycle 1 Day 1 [C1D1])
Hemoglobin ≥8.0 mg/dL without red blood cell transfusion ≤3 days prior to C1D1
Total serum bilirubin≤ 1.5 X upper limit of normal (ULN)
AST (SGOT)/ALT (SGPT)≤2 X ULN; ≤5 X ULN if there is liver involvement secondary to tumore. Serum creatinine ≤1.5 X ULN (OR creatinine clearance ≥60mL/min/1.73m2) Arm D: As patients are continuing treatment with ONC201 and met original referring study inclusion criteria, patients will not be prevented from enrolling based on above organ function criteria; however any patient with values not meeting these thresholds should be discussed with the medical monitor.
For patients post pubertal: Female patients must agree to use effective contraception while taking ONC201 and for at least 90 days after completion of treatment. Male patients must be surgically sterile or must agree to use effective contraception while taking ONC201 and for at least 90 days after completion of treatment. The decision of effective contraception will be based on the judgment of the principal investigator.
Ability to understand a written informed consent document, and the willingness to sign it. Assent will be obtained when appropriate based on the patient age.
Qualifies for participation in an ongoing ONC201 or ONC206 clinical trial. Arm D: Not applicable.
Previously or current enrollment in an ONC201 clinical trial (including open-label and blinded studies) or expanded access protocol or previous exposure to ONC201 from any source.
Arm D: Not applicable.
Current or planned participation in a study of an investigational agent (including ONC206) or using an investigational device.
Arm D: investigational agent does not include use of ONC201 in the referring study.
(Not applicable; criterion removed in Amendment 4)
Any known systemic infection that, in the opinion of the investigator, could compromise the safety of the patient, while taking ONC201.
Prolongation of QT/QTcF interval (QTc interval >480 milliseconds) using Fridericia's QT correction formula on two ECGs separated by at least 2 days.
Arm D: ECGs are not required for Arm D unless clinically indicated during screening.
A history of Torsades de Pointes or heart failure, hypokalemia, or family history of prolonged QT Syndrome
Concomitant use of medication(s) known to prolong the QT/QTc interval.