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ONC201 in Pediatric H3 K27M Gliomas

Primary Purpose

Diffuse Intrinsic Pontine Glioma, Glioma, Malignant

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ONC201
Sponsored by
Chimerix
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Intrinsic Pontine Glioma

Eligibility Criteria

2 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. 2 to less than 19 years of age.
  2. Patient body weight must be above the minimum necessary for the patient to receive the ONC201 dose indicated for the currently enrolling dose level. The minimum body weight ranges from 10-27.5kg depending on the dose level.
  3. Arm A and G: Patients with glioma who are positive for the H3 K27M mutation (positive testing in CLIA laboratory) and have completed at least one line of prior therapy. Evidence of progression is not required so that ONC201 may be administered to patients in the maintenance setting or to patients with recurrent disease. No more than two episodes of recurrence from radiotherapy and/or chemotherapy are allowed. Use of bevacizumab solely for treatment of radiation necrosis, pseudoprogression, or treatment effect will not be considered a recurrence. Post-mortem biopsy is required if H3 K27M status of tumor is unknown and archival tumor tissue not available.

    Arm B: Patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter and diffuse involvement of the pons, are eligible with or without histologic confirmation. Post-mortem biopsy is required if H3 K27M status of tumor is unknown and archival tumor tissue not available.

    Arm C: Patients with midline gliomas are eligible with or without histologic confirmation and must be eligible for tumor biopsy as deemed by the site Investigator.

    Arm D: Patients with recurrent glioma who are positive for the H3 K27M mutation (positive testing in CLIA laboratory), have completed at least one line of prior therapy, must be willing to undergo serial lumbar puncture to obtain cerebrospinal fluid (CSF), and must be scheduled to undergo sedated MRIs. Local anesthesia for spinal tap is also allowed. Evidence of progression is not required so that ONC201 may be administered to patients in the maintenance setting or to patients with recurrent disease. No more than two prior episodes of recurrence from radiotherapy and/or chemotherapy are allowed. Use of bevacizumab solely for treatment of radiation necrosis, pseudoprogression, or treatment effect will not be considered a recurrence. Spinal tap should not be performed if treating clinician or lumbar puncture proceduralist has concern of signs of elevated intracranial pressure, including recent worsening in headache or somnolence.

    Arm E: Patients with glioma who are positive for the H3 K27M mutation (positive testing in CLIA laboratory) or have diagnosed diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter and diffuse involvement of the pons, are eligible with or without histologic confirmation. Patients must be 2-12 weeks from completion of first-line radiation. Evidence of progression is not required so that ONC201 may be administered to patients in the maintenance setting or to patients with recurrent disease.

    Arm F:

    Pediatric patients with histologically confirmed diagnosis of high-grade glioma in any tumor sample with a known histone H3 K27M mutation identified by IHC or DNA sequencing test performed in a CLIA setting. Evidence of progressive disease on contrast-enhanced brain MRI as defined by RANO-HGG criteria is required. Patients must have had previous therapy with at least radiotherapy.

  4. Karnofsky ≥ 50 for patients ≥ 16 years of age, and Lansky ≥ 50 for patients < 16 years of age. For Arm F, Karnofsky ≥ 60 for patients ≥ 16 years of age, and Lansky ≥ 60 for patients < 16 years of age
  5. From the projected start of scheduled study treatment, the following time periods must have elapsed: 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 antibodies, or 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies. For patients who have received radiotherapy, patients in any arm must be at least 2 weeks from the completion of local palliative radiotherapy (re-irradiation for progressive disease or upfront radiation at initial diagnosis). For Arm F, patients must be at least 90 days from prior radiation to the first dose of ONC201unless the progressive lesion is outside of the high-dose radiation target volume or there is unequivocal evidence of progressive tumor on a biopsy specimen.
  6. Adequate organ function defined as:

    Bone Marrow:

    • Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3 and
    • Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).

    Renal Function:

    • Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70mL/min/1.73 m2 or normal serum creatinine based on age as shown below or GFR > 70ml/min/1.73m^2: Age < 5 years: 0.8 mg/dL maximum Age 5 to < 10 years: 1.0 mg/dL maximum Age 10 to < 15 years: 1.2 mg/dL maximum Age > 15 years: 1.5 mg/dL maximum

    Liver Function:

    • Total Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of institutional normal and
    • SGPT (ALT) ≤ 110 U/L and
    • Serum albumin ≥ 2 g/dL.

    Neurologic Function:

    • Patients with seizure disorder may be enrolled if seizure disorder is well controlled.

  7. Ability to understand a written informed consent document, and the willingness to sign it. Assent will be obtained when appropriate based on the subjects age.
  8. All adverse events Grade > 1 related to prior therapies (chemotherapy, radiotherapy, and/or surgery) must be resolved to grade 1 or baseline, except for alopecia and sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment, are acceptable.
  9. For patients post pubertal: Female patients must agree to use effective contraception during the period of the trial and for at least 90 days after completion of treatment. Male patients must be surgically sterile or must agree to use effective contraception during the period of the trial 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.
  10. Corticosteroid dose must be stable or decreasing for at least 3 days prior to the baseline CT or MRI scan.
  11. MRI brain and entire spine MRI within 14 days prior to start of study drug for Arms A, B, C, E, F and G. Subjects undergoing screening for Arm D must have an MRI of brain and entire spine within 3 months prior to start of study drug. Subjects in Arm D will have a baseline MRI of brain and spine with lumbar puncture after study consent is signed and other eligibility criteria are fulfilled.
  12. For Arms A, B, C, D, F and G: Ability to swallow and retain orally administered capsules.
  13. Archival tumor specimen: Subjects in all arms must submit at least 5 unstained slides from a tumor specimen that harbors H3 K27M mutation if archival tissue is available. For subjects in Arms A, B, E or G, if no archival tumor tissue is available, or if H3 K27M status of tumor is unknown, then subjects must agree to submit a post-mortem biopsy specimen. Subjects in Arm C do not require prior tumor biopsy or confirmation of the presence of the H3 K27M mutation. Subjects in Arm D must have confirmation of the presence of the H3 K27M mutation in any glioma sample prior to enrollment. Subjects in Arm F must submit at least 5 unstained slides from a tumor specimen that harbors H3 K27M mutation. Note that the H3 K27M mutation is often reported as H3 K28M in gene sequencing assays.

Exclusion Criteria:

  1. For Arms A, B, D, E, F and G: Evidence of diffuse leptomeningeal disease or evidence of CSF dissemination.
  2. Current or planned participation in a study of another investigational agent or using an investigational device.
  3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to ONC201 or its excipients.
  4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
  5. Any known clinically significant active infection including bacterial, fungal or viral including hepatitis B (HBV), hepatitis C (HCV) or any underlying disease or in the recent past which could compromise enrollment and safety of the patient
  6. Known history of cardiac arrhythmias including atrial fibrillation, tachyarrhythmias or bradycardia, unless arrhythmia is controlled and after Cardiology has cleared patient to receive ONC201. Receiving therapeutic agents known to prolong QT interval will be excluded, however the use of Zofran is permitted. History of CHF, or MI or stroke in the last 3 months will be excluded.
  7. Active illicit drug use or diagnosis of alcoholism.
  8. Known additional malignancy that is progressing or requires active treatment within 3 years of start of study drug.
  9. Concomitant use of potent CYP3A4/5 inhibitors during the treatment phase of the study and within 72 hours prior to starting study drug administration.
  10. Concomitant use of potent CYP3A4/5 inducers, which include enzyme inducing antiepileptic drugs (EIAEDs) (see Appendix B), during the treatment phase of the study and within 2 weeks prior to starting treatment. Concurrent dexamethasone is allowed.
  11. For Arm F: Exclusively non-contrast-enhancing disease or primary malignant lesion located in the pons or spinal cord.
  12. For Arm F: Atypical non-astrocytic histologies such as ependymoma, ganglioma and pleomorphic xanthoastrocytoma, pilocytic astrocytoma, or pilocytic astrocytoma and subependymal giant cell astrocytoma (SEGA).
  13. Prior treatment with ONC201

Sites / Locations

  • UCSF, Benioff Children's Hospital
  • Miami Cancer Institute
  • Children's Healthcare of Atlanta, Emory University School of Medicine
  • University of Michigan Cancer Center
  • New York University
  • Cincinnati Children's Hospital Medical Center
  • MD Anderson Cancer Center
  • Seattle Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

ONC201 in relapsed/refractory H3 K27M glioma

ONC201 in newly diagnosed DIPG

Midline Glioma Biopsy

H3 K27M CSF Biopsy

Liquid ONC201 in relapsed/refractory H3 K27M glioma

Dose Expansion Cohort in relapsed/refractory H3 K27M glioma

ONC201 given on two consecutive days of each week

Arm Description

Pediatric patients with glioma who are positive for the H3 K27M mutation (positive testing in CLIA laboratory) and have completed at least one line of prior therapy. Evidence of progression is not required so that ONC201 may be administered to patients in the maintenance setting or to patients with recurrent/refractory disease.

Pediatric patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter and diffuse involvement of the pons, are eligible with or without histologic confirmation. If H3 K27M status of tumor is unknown or archival tumor tissue is not available, then patients must agree to submit a post-mortem biopsy specimen.

Pediatric patients midline gliomas are eligible with or without histologic confirmation and must be eligible for tumor biopsy as deemed by the site Investigator.

Pediatric patients with recurrent glioma who are positive for the H3 K27M mutation (positive testing in CLIA laboratory), have completed at least one line of prior therapy, must be willing to undergo serial lumbar puncture to obtain cerebrospinal fluid (CSF), and must be scheduled to undergo sedated MRIs.

Patients with glioma who are positive for the H3 K27M mutation (positive testing in CLIA laboratory) or have diagnosed diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter and diffuse involvement of the pons, are eligible with or without histologic confirmation. Patients must be 2-12 weeks from completion of first-line radiation.

Pediatric patients with previously-treated, histologically confirmed high-grade glioma with a known H3 K27M mutation, evidence of progressive disease contrast-enhanced brain MRI as defined by RANO-HGG criteria. Prior therapy with at least radiotherapy is required.

Pediatric patients with glioma who are positive for the H3 K27M mutation (positive testing in CLIA laboratory) and have completed at least one line of prior therapy will be enrolled to define the RP2D for single agent ONC201 given on two consecutive days of each week.

Outcomes

Primary Outcome Measures

RP2D
Determination of recommended Phase 2 dose (RP2D) as a single agent or in combination with radiation

Secondary Outcome Measures

Full Information

First Posted
January 23, 2018
Last Updated
August 11, 2023
Sponsor
Chimerix
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1. Study Identification

Unique Protocol Identification Number
NCT03416530
Brief Title
ONC201 in Pediatric H3 K27M Gliomas
Official Title
ONC201 in Newly Diagnosed Diffuse Intrinsic Pontine Glioma and Recurrent/Refractory Pediatric H3 K27M Gliomas
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 29, 2018 (Actual)
Primary Completion Date
August 31, 2023 (Anticipated)
Study Completion Date
September 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Chimerix

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This is a multicenter, open-label, seven arm, dose escalation, phase I study of oral ONC201 in pediatric patients with newly diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) and recurrent/refractory H3 K27M gliomas. Arm A will define the RP2D for single agent ONC201 in pediatric patients with glioma who are positive for the H3 K27M mutation (positive testing in CLIA laboratory) and have completed at least one line of prior therapy. This will allow for recurrent patients and also patients who have not yet recurred, but have completed radiation and will inevitably recur based on prior clinical experience and the literature. Arm B will define the RP2D for ONC201 in combination with radiation in pediatric patients with newly diagnosed DIPG. Arm C will determine intratumoral drug concentrations and biomarker expression in pediatric patients with midline gliomas. Arm D will determine H3 K27M DNA levels and drug concentrations in the CSF of pediatric H3 K27M-mutant glioma patients. Arm E will determine the RP2D for single agent ONC201 administered as a liquid formulation in Ora-Sweet to patients with DIPG and/or H3 K27M glioma. Arm F is a dose expansion cohort to confirm the safety and estimate the efficacy in recurrent H3 K27M-mutant glioma population at the RP2D. Arm G will define the RP2D for single agent ONC201 given on two consecutive days of each week in pediatric patients with glioma who are positive for the H3 K27M mutation and have completed at least one line of prior therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Intrinsic Pontine Glioma, Glioma, Malignant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
130 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
ONC201 in relapsed/refractory H3 K27M glioma
Arm Type
Experimental
Arm Description
Pediatric patients with glioma who are positive for the H3 K27M mutation (positive testing in CLIA laboratory) and have completed at least one line of prior therapy. Evidence of progression is not required so that ONC201 may be administered to patients in the maintenance setting or to patients with recurrent/refractory disease.
Arm Title
ONC201 in newly diagnosed DIPG
Arm Type
Experimental
Arm Description
Pediatric patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter and diffuse involvement of the pons, are eligible with or without histologic confirmation. If H3 K27M status of tumor is unknown or archival tumor tissue is not available, then patients must agree to submit a post-mortem biopsy specimen.
Arm Title
Midline Glioma Biopsy
Arm Type
Experimental
Arm Description
Pediatric patients midline gliomas are eligible with or without histologic confirmation and must be eligible for tumor biopsy as deemed by the site Investigator.
Arm Title
H3 K27M CSF Biopsy
Arm Type
Experimental
Arm Description
Pediatric patients with recurrent glioma who are positive for the H3 K27M mutation (positive testing in CLIA laboratory), have completed at least one line of prior therapy, must be willing to undergo serial lumbar puncture to obtain cerebrospinal fluid (CSF), and must be scheduled to undergo sedated MRIs.
Arm Title
Liquid ONC201 in relapsed/refractory H3 K27M glioma
Arm Type
Experimental
Arm Description
Patients with glioma who are positive for the H3 K27M mutation (positive testing in CLIA laboratory) or have diagnosed diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter and diffuse involvement of the pons, are eligible with or without histologic confirmation. Patients must be 2-12 weeks from completion of first-line radiation.
Arm Title
Dose Expansion Cohort in relapsed/refractory H3 K27M glioma
Arm Type
Experimental
Arm Description
Pediatric patients with previously-treated, histologically confirmed high-grade glioma with a known H3 K27M mutation, evidence of progressive disease contrast-enhanced brain MRI as defined by RANO-HGG criteria. Prior therapy with at least radiotherapy is required.
Arm Title
ONC201 given on two consecutive days of each week
Arm Type
Experimental
Arm Description
Pediatric patients with glioma who are positive for the H3 K27M mutation (positive testing in CLIA laboratory) and have completed at least one line of prior therapy will be enrolled to define the RP2D for single agent ONC201 given on two consecutive days of each week.
Intervention Type
Drug
Intervention Name(s)
ONC201
Intervention Description
ONC201 is a orally active, small molecule DRD2 antagonist that kills cancer cells but not normal cells.
Primary Outcome Measure Information:
Title
RP2D
Description
Determination of recommended Phase 2 dose (RP2D) as a single agent or in combination with radiation
Time Frame
28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 2 to less than 19 years of age. Patient body weight must be above the minimum necessary for the patient to receive the ONC201 dose indicated for the currently enrolling dose level. The minimum body weight ranges from 10-27.5kg depending on the dose level. Arm A and G: Patients with glioma who are positive for the H3 K27M mutation (positive testing in CLIA laboratory) and have completed at least one line of prior therapy. Evidence of progression is not required so that ONC201 may be administered to patients in the maintenance setting or to patients with recurrent disease. No more than two episodes of recurrence from radiotherapy and/or chemotherapy are allowed. Use of bevacizumab solely for treatment of radiation necrosis, pseudoprogression, or treatment effect will not be considered a recurrence. Post-mortem biopsy is required if H3 K27M status of tumor is unknown and archival tumor tissue not available. Arm B: Patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter and diffuse involvement of the pons, are eligible with or without histologic confirmation. Post-mortem biopsy is required if H3 K27M status of tumor is unknown and archival tumor tissue not available. Arm C: Patients with midline gliomas are eligible with or without histologic confirmation and must be eligible for tumor biopsy as deemed by the site Investigator. Arm D: Patients with recurrent glioma who are positive for the H3 K27M mutation (positive testing in CLIA laboratory), have completed at least one line of prior therapy, must be willing to undergo serial lumbar puncture to obtain cerebrospinal fluid (CSF), and must be scheduled to undergo sedated MRIs. Local anesthesia for spinal tap is also allowed. Evidence of progression is not required so that ONC201 may be administered to patients in the maintenance setting or to patients with recurrent disease. No more than two prior episodes of recurrence from radiotherapy and/or chemotherapy are allowed. Use of bevacizumab solely for treatment of radiation necrosis, pseudoprogression, or treatment effect will not be considered a recurrence. Spinal tap should not be performed if treating clinician or lumbar puncture proceduralist has concern of signs of elevated intracranial pressure, including recent worsening in headache or somnolence. Arm E: Patients with glioma who are positive for the H3 K27M mutation (positive testing in CLIA laboratory) or have diagnosed diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter and diffuse involvement of the pons, are eligible with or without histologic confirmation. Patients must be 2-12 weeks from completion of first-line radiation. Evidence of progression is not required so that ONC201 may be administered to patients in the maintenance setting or to patients with recurrent disease. Arm F: Pediatric patients with histologically confirmed diagnosis of high-grade glioma in any tumor sample with a known histone H3 K27M mutation identified by IHC or DNA sequencing test performed in a CLIA setting. Evidence of progressive disease on contrast-enhanced brain MRI as defined by RANO-HGG criteria is required. Patients must have had previous therapy with at least radiotherapy. Karnofsky ≥ 50 for patients ≥ 16 years of age, and Lansky ≥ 50 for patients < 16 years of age. For Arm F, Karnofsky ≥ 60 for patients ≥ 16 years of age, and Lansky ≥ 60 for patients < 16 years of age From the projected start of scheduled study treatment, the following time periods must have elapsed: 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 antibodies, or 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies. For patients who have received radiotherapy, patients in any arm must be at least 2 weeks from the completion of local palliative radiotherapy (re-irradiation for progressive disease or upfront radiation at initial diagnosis). For Arm F, patients must be at least 90 days from prior radiation to the first dose of ONC201unless the progressive lesion is outside of the high-dose radiation target volume or there is unequivocal evidence of progressive tumor on a biopsy specimen. Adequate organ function defined as: Bone Marrow: Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3 and Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment). Renal Function: • Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70mL/min/1.73 m2 or normal serum creatinine based on age as shown below or GFR > 70ml/min/1.73m^2: Age < 5 years: 0.8 mg/dL maximum Age 5 to < 10 years: 1.0 mg/dL maximum Age 10 to < 15 years: 1.2 mg/dL maximum Age > 15 years: 1.5 mg/dL maximum Liver Function: Total Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of institutional normal and SGPT (ALT) ≤ 110 U/L and Serum albumin ≥ 2 g/dL. Neurologic Function: • Patients with seizure disorder may be enrolled if seizure disorder is well controlled. Ability to understand a written informed consent document, and the willingness to sign it. Assent will be obtained when appropriate based on the subjects age. All adverse events Grade > 1 related to prior therapies (chemotherapy, radiotherapy, and/or surgery) must be resolved to grade 1 or baseline, except for alopecia and sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment, are acceptable. For patients post pubertal: Female patients must agree to use effective contraception during the period of the trial and for at least 90 days after completion of treatment. Male patients must be surgically sterile or must agree to use effective contraception during the period of the trial 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. Corticosteroid dose must be stable or decreasing for at least 3 days prior to the baseline CT or MRI scan. MRI brain and entire spine MRI within 14 days prior to start of study drug for Arms A, B, C, E, F and G. Subjects undergoing screening for Arm D must have an MRI of brain and entire spine within 3 months prior to start of study drug. Subjects in Arm D will have a baseline MRI of brain and spine with lumbar puncture after study consent is signed and other eligibility criteria are fulfilled. For Arms A, B, C, D, F and G: Ability to swallow and retain orally administered capsules. Archival tumor specimen: Subjects in all arms must submit at least 5 unstained slides from a tumor specimen that harbors H3 K27M mutation if archival tissue is available. For subjects in Arms A, B, E or G, if no archival tumor tissue is available, or if H3 K27M status of tumor is unknown, then subjects must agree to submit a post-mortem biopsy specimen. Subjects in Arm C do not require prior tumor biopsy or confirmation of the presence of the H3 K27M mutation. Subjects in Arm D must have confirmation of the presence of the H3 K27M mutation in any glioma sample prior to enrollment. Subjects in Arm F must submit at least 5 unstained slides from a tumor specimen that harbors H3 K27M mutation. Note that the H3 K27M mutation is often reported as H3 K28M in gene sequencing assays. Exclusion Criteria: For Arms A, B, D, E, F and G: Evidence of diffuse leptomeningeal disease or evidence of CSF dissemination. Current or planned participation in a study of another investigational agent or using an investigational device. History of allergic reactions attributed to compounds of similar chemical or biologic composition to ONC201 or its excipients. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements. Any known clinically significant active infection including bacterial, fungal or viral including hepatitis B (HBV), hepatitis C (HCV) or any underlying disease or in the recent past which could compromise enrollment and safety of the patient Known history of cardiac arrhythmias including atrial fibrillation, tachyarrhythmias or bradycardia, unless arrhythmia is controlled and after Cardiology has cleared patient to receive ONC201. Receiving therapeutic agents known to prolong QT interval will be excluded, however the use of Zofran is permitted. History of CHF, or MI or stroke in the last 3 months will be excluded. Active illicit drug use or diagnosis of alcoholism. Known additional malignancy that is progressing or requires active treatment within 3 years of start of study drug. Concomitant use of potent CYP3A4/5 inhibitors during the treatment phase of the study and within 72 hours prior to starting study drug administration. Concomitant use of potent CYP3A4/5 inducers, which include enzyme inducing antiepileptic drugs (EIAEDs) (see Appendix B), during the treatment phase of the study and within 2 weeks prior to starting treatment. Concurrent dexamethasone is allowed. For Arm F: Exclusively non-contrast-enhancing disease or primary malignant lesion located in the pons or spinal cord. For Arm F: Atypical non-astrocytic histologies such as ependymoma, ganglioma and pleomorphic xanthoastrocytoma, pilocytic astrocytoma, or pilocytic astrocytoma and subependymal giant cell astrocytoma (SEGA). Prior treatment with ONC201
Facility Information:
Facility Name
UCSF, Benioff Children's Hospital
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Miami Cancer Institute
City
Miami
State/Province
Florida
ZIP/Postal Code
33176
Country
United States
Facility Name
Children's Healthcare of Atlanta, Emory University School of Medicine
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Michigan Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
New York University
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
35137228
Citation
Cantor E, Wierzbicki K, Tarapore RS, Ravi K, Thomas C, Cartaxo R, Nand Yadav V, Ravindran R, Bruzek AK, Wadden J, John V, May Babila C, Cummings JR, Rahman Kawakibi A, Ji S, Ramos J, Paul A, Walling D, Leonard M, Robertson P, Franson A, Mody R, Garton HJL, Venneti S, Odia Y, Kline C, Vitanza NA, Khatua S, Mueller S, Allen JE, Gardner SL, Koschmann C. Serial H3K27M cell-free tumor DNA (cf-tDNA) tracking predicts ONC201 treatment response and progression in diffuse midline glioma. Neuro Oncol. 2022 Aug 1;24(8):1366-1374. doi: 10.1093/neuonc/noac030.
Results Reference
derived

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ONC201 in Pediatric H3 K27M Gliomas

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