Research into a new treatment for children and young adults with diffuse midline glioma
- Conditions
- Diffuse Midline Gliomas, H3K27M mutantMedDRA version: 21.1Level: PTClassification code 10065443Term: Malignant gliomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10006143Term: Brain stem gliomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: LLTClassification code 10080666Term: Diffuse intrinsic pontine gliomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2022-000636-40-NL
- Lead Sponsor
- Pacific Pediatric Neuro-Oncology Consortium (PNOC)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 324
Cohort 1A and 1B (participants with newly diagnosed DMG prior to radiation therapy)
-New diagnosis of DMG with imaging and/or pathology consistent with a DMG, including spinal cord tumors. In cohort 1B, previous tumor tissue confirmation of DMG is mandatory and pathology must be consistent with a DMG including diffuse midline glioma H3K27M mutant; WHO Grade 3 and 4 H3 wildtype gliomas.
Cohort 2A and 2B (participants with DMG who have completed radiation therapy)
-Diagnosis of DMG with imaging and/or pathology consistent with a DMG, including spinal cord tumors, who have completed standard-of-care radiation therapy. In cohort 2B, previous tumor tissue confirmation of DMG is mandatory and pathology must be consistent with a DMG including diffuse midline glioma H3K27M mutant; WHO Grade 3 and 4 H3 wildtype gliomas.
-Participants must be within 4-14 weeks of completion of radiation.
Cohort 3A and 3B (participants with DMG at progression)
-Diagnosis of recurrent DMG with imaging and/or pathology consistent with a DMG, including spinal cord tumors, who have completed standard-of-care radiation therapy. In Cohort 3B, previous tumor tissue confirmation of DMG is mandatory and pathology must be consistent with a DMG including diffuse midline glioma H3K27M mutant; WHO Grade 3 and 4 H3 wildtype gliomas.
-Participants must have evidence of progression and not have received any treatment for this
progression and have not previously received re-irradiation.
Are the trial subjects under 18? yes
Number of subjects for this age range: 275
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 49
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Cohort 1A and 1B (participants with newly diagnosed DMG prior to radiation therapy)
-Prior exposure to radiation therapy.
-Thalamic H3K27M DMG*
Cohort 2A and 2B
-For tumors that do not have a pontine or spinal cord epicenter the following specific exclusion criteria apply:
--Thalamic H3K27M DMG that has undergone standard radiation without concurrent therapy (other than temozolomide)*
Cohort 1A and 2A (participants with newly diagnosed DMG prior to radiation therapy and who have not previously undergone tumor tissue collection prior to study entry)
-Deemed not appropriate for tissue resection/biopsy.
Cohort 3A and 3B (participants with DMG at progression)
-Prior exposure to re-irradiation for tumor progression.
-Patients who participated in trials investigating ONC201 in the upfront setting will not be eligible. Prior ONC201 exposure as part of PNOC022 or expanded access programs will be allowed.*
All Cohorts
-Diagnosis of a histone H3 wildtype Grade 2 diffuse astrocytoma
-Investigational Drugs
o Participants who are currently receiving another investigational drug. Investigational imaging agents or agents used to enhance tumor visibility on imaging or during tumor biopsy/resection should be discussed with the study chairs.
-Anti-cancer Agents
o Participants who are currently receiving other anti-cancer agents.
-Participants with a known disorder that affects their immune system, such as HIV or Hepatitis B or C, or an auto-immune disorder requiring systemic cytotoxic or immunosuppressive therapy. Note: Participants that are currently using inhaled, intranasal, ocular, topical or other non-oral or non-IV steroids are not necessarily excluded from the
study but need to be discussed with the study chair.
-Participants with uncontrolled infection or other uncontrolled systemic illness.
-Female participants of childbearing potential must not be pregnant or breast-feeding. Female participants of childbearing potential must have a negative serum or urine pregnancy test prior to the start of therapy (as clinically indicated).
-Active illicit drug use or diagnosis of alcoholism.
-History of allergic reactions attributed to compounds of similar chemical or biologic composition as the agents used in study.
-Evidence of disseminated disease, including multi-focal disease, diffuse leptomeningeal disease or evidence of CSF dissemination.
-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 I), during the treatment phase of the study and within 2 weeks prior to starting treatment. Concurrent corticosteroids is allowed.
*Exclusion criteria do not apply to patient of =18 years old who have thalamic disease; these patients can still be included in the PNOC022 trial at the Prinses Máxima Center. Exclusion criteria do apply to patients over the age of 18 years old who have thalamic disease. These patients can be enrolled in the ACTION trial.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method