This partially randomized phase III trial is studying maintenance chemotherapy to see how well it works compared to observation following induction chemotherapy and radiation therapy in treating young patients with newly diagnosed ependymoma. Drugs used in chemotherapy, such as vincristine sulfate, carboplatin, cyclophosphamide, etoposide, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Giving chemotherapy with radiation therapy may kill more tumor cells and allow doctors to save the part of the body where the cancer started.

NCT01096368

Conditions

1. Anaplastic Ependymoma
2. Brain Ependymoma
3. Cellular Ependymoma
4. Clear Cell Ependymoma
5. Ependymoma
6. Papillary Ependymoma

Interventions

1. Radiation: 3-Dimensional Conformal Radiation Therapy
2. Drug: Carboplatin
3. Drug: Cisplatin
4. Other: Clinical Observation
5. Drug: Cyclophosphamide
6. Drug: Etoposide
7. Other: Laboratory Biomarker Analysis
8. Drug: Vincristine

MeSH:Ependymoma

HPO:Ependymoma

V. To evaluate biologic prognostic factors in childhood ependymoma by studying molecular groups as defined by deoxyribonucleic acid (DNA) methylation profiling and immunohistochemistry, copy number variants to identify 1q gain in posterior fossa ependymomas, CDKN2A loss (homozygous deletion) in supratentorial ependymomas and specific genetic alterations such as RELA fusions, YAP1 fusions and the H3 K27M mutation on initial tumor samples and correlating these data with clinical outcome. --- K27M ---

This phase I trial studies the side effects and the best dose of adavosertib when given together with local radiation therapy in treating children with newly diagnosed diffuse intrinsic pontine gliomas. Adavosertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays, gamma rays, neutrons, protons, or other sources to kill tumor cells and shrink tumors. Giving adavosertib with local radiation therapy may work better than local radiation therapy alone in treating diffuse intrinsic pontine gliomas.

NCT01922076

Conditions

1. Anaplastic Astrocytoma
2. Anaplastic Oligoastrocytoma
3. Diffuse Intrinsic Pontine Glioma
4. Diffuse Midline Glioma, H3 K27M-Mutant
5. Glioblastoma
6. Gliosarcoma

Interventions

1. Drug: Adavosertib
2. Other: Laboratory Biomarker Analysis
3. Other: Pharmacological Study
4. Radiation: Radiation Therapy

MeSH:Glioblastoma Glioma Astrocytoma Gliosarcoma

HPO:Astrocytoma Glioblastoma multiforme Glioma Subependymal giant-cell astrocytoma

Paired analysis methods will be used.. Inclusion Criteria: - Patients with newly diagnosed DIPGs, defined as tumors with a pontine epicenter and diffuse involvement of the pons, are eligible without histologic confirmation - Patients with brainstem tumors that do not meet these criteria or are not considered to be typical intrinsic pontine gliomas will only be eligible if the tumors are biopsied and proven to be an anaplastic astrocytoma, glioblastoma, gliosarcoma, diffuse midline glioma with histone H3 K27M mutation, or anaplastic mixed glioma; patients with pilocytic astrocytoma, fibrillary astrocytoma, gangliogliomas, or other mixed gliomas without anaplasia are not eligible - Patients with disseminated disease are not eligible, and magnetic resonance imaging (MRI) of spine must be performed if disseminated disease is suspected by the treating physician - Enrollment must be no later than 28 days after the date of radiographic diagnosis or surgery, whichever is the later date - Patients must have a body surface area >= 0.35 m^2 at the time of study enrollment - Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score - Patients must not have received any prior anti-cancer therapy such as chemotherapy, radiation therapy, immunotherapy or bone marrow transplant for the treatment of DIPG; prior dexamethasone and/or surgery are allowed - Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 - Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 --- K27M ---

congestive heart failure, acute myocardial infarction, significant uncontrolled arrhythmias) are not eligible for this trial - Major surgical procedures =< 28 days of beginning study treatment, or minor surgical procedures (including ventriculoperitoneal [VP] shunt placement or stereotactic biopsy of the tumor) =< 7 days; no waiting period required following port-a-cath or other central venous access placement - Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible Inclusion Criteria: - Patients with newly diagnosed DIPGs, defined as tumors with a pontine epicenter and diffuse involvement of the pons, are eligible without histologic confirmation - Patients with brainstem tumors that do not meet these criteria or are not considered to be typical intrinsic pontine gliomas will only be eligible if the tumors are biopsied and proven to be an anaplastic astrocytoma, glioblastoma, gliosarcoma, diffuse midline glioma with histone H3 K27M mutation, or anaplastic mixed glioma; patients with pilocytic astrocytoma, fibrillary astrocytoma, gangliogliomas, or other mixed gliomas without anaplasia are not eligible - Patients with disseminated disease are not eligible, and magnetic resonance imaging (MRI) of spine must be performed if disseminated disease is suspected by the treating physician - Enrollment must be no later than 28 days after the date of radiographic diagnosis or surgery, whichever is the later date - Patients must have a body surface area >= 0.35 m^2 at the time of study enrollment - Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score - Patients must not have received any prior anti-cancer therapy such as chemotherapy, radiation therapy, immunotherapy or bone marrow transplant for the treatment of DIPG; prior dexamethasone and/or surgery are allowed - Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 - Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 --- K27M ---

congestive heart failure, acute myocardial infarction, significant uncontrolled arrhythmias) are not eligible for this trial - Major surgical procedures =< 28 days of beginning study treatment, or minor surgical procedures (including ventriculoperitoneal [VP] shunt placement or stereotactic biopsy of the tumor) =< 7 days; no waiting period required following port-a-cath or other central venous access placement - Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible Anaplastic Astrocytoma Anaplastic Oligoastrocytoma Diffuse Intrinsic Pontine Glioma Diffuse Midline Glioma, H3 K27M-Mutant Glioblastoma Gliosarcoma Glioblastoma Glioma Astrocytoma Gliosarcoma PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose (MTD) or recommended phase 2 dose and schedule of the adavosertib (Wee1 inhibitor AZD1775 [MK-1775]) administered concurrently with radiation therapy in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG). --- K27M ---

ONC201 is a new drug candidate that kills cancer cells but not normal cells in laboratory studies and has been previously evaluated in a phase I clinical trial in advanced cancer patients. This clinical trial will enroll patients with recurrent glioblastoma or recurrent WHO Grade IV gliomas with the H3 K27M mutation.

NCT02525692

Conditions

1. Glioblastoma
2. Diffuse Midline Glioma
3. H3 K27M Glioma
4. Thalamic Glioma
5. Infratentorial Glioma
6. Basal Ganglia Glioma

Interventions

1. Drug: ONC201

MeSH:Glioblastoma Glioma

HPO:Glioblastoma multiforme Glioma

Oral ONC201 in Recurrent Glioblastoma, H3 K27M-mutant Glioma, and Diffuse Midline Glioma. --- K27M ---

Oral ONC201 in Recurrent GBM, H3 K27M Glioma, and Midline Glioma ONC201 is a new drug candidate that kills cancer cells but not normal cells in laboratory studies and has been previously evaluated in a phase I clinical trial in advanced cancer patients. --- K27M ---

This clinical trial will enroll patients with recurrent glioblastoma or recurrent WHO Grade IV gliomas with the H3 K27M mutation. --- K27M ---

For Arm D: Must have a WHO Grade IV glioma as per above and tumor must harbor a histone H3 K27M mutation as evidenced by testing any tumor sample with an immunohistochemistry or DNA sequencing test. --- K27M ---

For Arm F: Must have a diffuse midline glioma, defined as a WHO Grade IV glioma involving the brainstem, thalamus or spinal cord, without the H3 K27M mutation or with unknown H3 mutation status. --- K27M ---

Glioblastoma Diffuse Midline Glioma H3 K27M Glioma Thalamic Glioma Infratentorial Glioma Basal Ganglia Glioma Glioblastoma Glioma null --- K27M ---

In this research study the investigators want to learn more about the effects, both good and bad, when the study drug Ribociclib is given after radiation therapy. The investigators are asking people to be in this research study that have been newly diagnosed with a high grade glioma, and the tumor has been screened for the Rb1 protein, and have recently finished radiation therapy. Patients with a DIPG or a Bi-thalamic high grade glioma do not need to have tumor tissue screened for the Rb1 protein but do need to have finished radiation therapy. Tumor cells grow and divide quickly. In normal cells, there are proteins called cyclin-dependent kinases (CDK 4 and 6) that control cell division. Another protein Rb1 also controls cell division and works to stop cells from dividing so they do not become cancer cells. But in cancer, the CDK 4 and 6 proteins are out of control making the cells divide and grow quickly. The study drug, ribociclib stops the CDK 4 and 6 proteins. When the CDK 4 and 6 proteins are stopped, the normal Rb1 protein can now work to slow cell growth. For patients with HGG, to be in this study tumor tissue must have a normal Rb1 protein. The researchers think that if the study drug is given soon after radiation therapy, it may help improve the effect of the radiation in stopping the tumor from growing. The study drug, Ribociclib is considered investigational as it has not yet been approved by the United States Food and Drug Administration. The study drug has been tested in children and adults with cancer in prior research studies.

NCT02607124

Conditions

1. High Grade Glioma
2. Diffuse Intrinsic Pontine Glioma
3. Bithalamic High Grade Glioma

Interventions

1. Drug: Ribociclib

MeSH:Glioma

HPO:Glioma

- Patients with brainstem tumors that do not meet these criteria or not considered to be typical intrinsic pontine gliomas will only be eligible if the tumors are biopsied and proven to have + RB and be the following according to the 2016 World Health Organization classification of tumors of the central nervous system: an anaplastic astrocytoma (IDH mutant, IDH wildtype, or NOS), glioblastoma (IDH mutant, IDH wildtype or NOS), diffuse midline glioma, H3 K27M mutant or H3 K27M negative, diffuse astrocytoma (IDH mutant, IDH wildtype or NOS). --- K27M ---

- Patients with brainstem tumors that do not meet these criteria or not considered to be typical intrinsic pontine gliomas will only be eligible if the tumors are biopsied and proven to have + RB and be the following according to the 2016 World Health Organization classification of tumors of the central nervous system: an anaplastic astrocytoma (IDH mutant, IDH wildtype, or NOS), glioblastoma (IDH mutant, IDH wildtype or NOS), diffuse midline glioma, H3 K27M mutant or H3 K27M negative, diffuse astrocytoma (IDH mutant, IDH wildtype or NOS). --- K27M --- --- K27M ---

This phase I trial studies the side effects and best dose of panobinostat in treating younger patients with diffuse intrinsic pontine glioma (DIPG). Panobinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Stratum 1 treats patients with DIPG that has returned or gotten worse (progressed). Stratum 2 treats patients with DIPG that has not yet gotten worse. Currently, only Stratum 2 is enrolling patients.

NCT02717455

Conditions

1. Glioma

Interventions

1. Drug: LBH589

MeSH:Glioma

HPO:Glioma

To identify histone 3 K27M mutations in peripheral blood and urine, and evaluate changes with treatment.. Pharmacodynamics: Cell-free DNA - Blood and Urine (Optional). --- K27M ---

Based on the in vitro and in vivo activity of panobinostat in preclinical models using DIPG cell cultures and orthotopic xenograft model systems, and the potentially important role of histone deacetylases and histone 3 K27M mutations in relation to pontine malignancies, the investigators are conducting a Phase 1 study of panobinostat in children with recurrent/progressive DIPG. --- K27M ---

This is 3-arm, multicenter study that will be conducted through the Pacific Pediatric Neuro-oncology Consortium (PNOC). This study will assess the safety and immune activity of a synthetic peptide vaccine specific for the H3.3.K27M epitope given in combination with poly-ICLC and the H3.3.K27M epitope given in combination with poly-ICLC and the PD-1 inhibitor, nivolumab, in HLA-A2 (02:01)+ children with newly diagnosed DIPG or other midline gliomas that are positive for H3.3K27M.

NCT02960230

Conditions

1. Diffuse Intrinsic Pontine Glioma
2. Glioma
3. Diffuse Midline Glioma, H3 K27M-Mutant

Interventions

1. Biological: K27M peptide
2. Drug: Nivolumab

MeSH:Glioma

HPO:Glioma

OS12 will be the clinical efficacy primary endpoint for Stratum A. Any eligible subject that receives at least one dose of the K27M/TT vaccine will be considered evaluable for clinical efficacy. --- K27M ---

Diffuse Intrinsic Pontine Glioma Glioma Diffuse Midline Glioma, H3 K27M-Mutant Glioma Subjects who are eligible will receive a specific peptide vaccine, along with a helper drug called poly-ICLC, in combination with nivolumab, every 3 weeks for the first 6 months of treatment. --- K27M ---

Doctors and other medical scientists want learn about the biology of DIPG/DMG and to develop better ways to diagnose and treat patients with DIPG/DMG. To do this, they need more information about the characteristics of DIPG/DMG tumors. Therefore, they want to establish a central location for clinical information and tumor tissue collected from DIPG/DMG patients. The purposes of this study are: - To enroll patients diagnosed with DIPG/DMG in the International DIPG/DMG Registry and Repository. - To provide a central location for clinical information, scans, and tissue samples from patients with DIPG/DMG enrolled in the registry. - To collect tissue samples in order to study how DIPG/DMG works on the molecular level. Researchers may use the tissue samples to study molecules such as proteins and DNA. Proteins are needed for the body to function properly and DNA is the molecule that carries our genetic information. Other researchers will be able to use the stored samples in the future to learn more about DIPG/DMG. The information researchers get from the research studies will be kept in the registry along with the clinical information. - To help investigators around the world to work together to make more consistent diagnosis and better design of future research studies. We hope this will lead to better treatments for DIPG/DMG in the future.

NCT03101813

Conditions

1. Diffuse Intrinsic Pontine Glioma
2. Diffuse Midline Glioma, H3 K27M-Mutant
3. Diffuse Midline Glioma

MeSH:Glioma

HPO:Glioma

Diffuse Intrinsic Pontine Glioma Diffuse Midline Glioma, H3 K27M-Mutant Diffuse Midline Glioma Glioma There are limited data regarding the biology of diffuse intrinsic pontine gliomas (DIPG) and diffuse midline gliomas (DMG). --- K27M ---

The objective of this expanded access program is to provide ONC201 to eligible patients with previously-treated glioma that exhibits the H3 K27M mutation and/or that is located in the midline region of the brain.

NCT03134131

Conditions

1. Glioma

Interventions

1. Drug: ONC201

MeSH:Glioma

HPO:Glioma

Expanded Access to ONC201 for Patients With H3 K27M-mutant and/or Midline High Grade Gliomas. --- K27M ---

Expanded Access to ONC201 for Patients With H3 K27M-mutant and/or Midline High Grade Gliomas The objective of this expanded access program is to provide ONC201 to eligible patients with previously-treated glioma that exhibits the H3 K27M mutation and/or that is located in the midline region of the brain. --- K27M ---

Expanded Access to ONC201 for Patients With H3 K27M-mutant and/or Midline High Grade Gliomas The objective of this expanded access program is to provide ONC201 to eligible patients with previously-treated glioma that exhibits the H3 K27M mutation and/or that is located in the midline region of the brain. --- K27M --- --- K27M ---

A glioma that is positive for the H3 K27M mutation (performed in a laboratory with CLIA certification); 2. A grade III or IV glioma involving the thalamus, hypothalamus, brainstem, cerebellum, midbrain, or spinal cord; 3. Diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter and diffuse involvement of the pons. --- K27M ---

The HIT-HGG-2013 trial offers an innovative high-quality diagnostics and science program for children and adolescents >3 years, suffering from one of the following types of high grade gliomas: 1. glioblastoma WHO grade IV (GBM) 2. diffuse midlineglioma histone 3 K27M mutated WHO grade IV (DMG) 3. anaplastic astrocytoma WHO grade III (AA) 4. diffuse intrinsic pontine glioma (DIPG) 5. gliomatosis cerebri (GC) For 1.-3. diagnosis has to be confirmed by neuropathological survey, for 4. and 5. diagnosis has to be confirmed by neuroradiological survey. In addition to standard treatment (radiotherapy and temozolomide chemotherapy) the effects of two further drugs, which have been applied to millions of children and adolescents in other indications, will be compared to each other. The aim of the trial will be to investigate whether these drugs may increase the effects of radio- and chemotherapy, resulting in a better survival of the treated patients. One of these additional drugs will be valproic acid, traditionally used for treatment of seizure disorder. The other drug will be Chloroquin, a well-established drug for Malaria treatment. Recently, scientific studies provided evidence for anti-tumoral effects of both drugs: Valproat seems to be a so-called histondeacetylase inhibitor (HDAC inhibitor), controlling important genetic processes of tumor growth. Chloroquin is an autophagy inhibitor. It prevents the shutting-down of tumor cell metabolism, a strategy to ensure survival of the whole tumor by developing a resistance against radiation and antineoplastic agents. Studies in cell culture, animals and first clinical trials in adults as well provided evidence for efficacy of valproic acid and chloroquine in the treatment of glioblastoma. Due to this we hope children and adolescents suffering from GBM, DMG, AA, DIPG und GC will benefit from the treatment, too. As common for clinical trials, the treatment of the patients will be settled in a randomized manner to ensure impartiality of the investigators. One aim of the HIT-HGG-2013 trial will be to compare the effects of Valproat and Chloroquin to each other. Additionally, the results will be compared with data of the HIT-HGG-2007 trial (children and adolescents with same diseases, only treated with simultaneous temozolomide radiochemotherapy).

NCT03243461

Conditions

1. Glioblastoma WHO Grade IV
2. Diffuse Midline Glioma Histone 3 K27M WHO Grade IV
3. Anaplastic Astrocytoma WHO Grade III
4. Diffuse Intrinsic Pontine Glioma
5. Gliomatosis Cerebri

Interventions

1. Drug: Temozolomide + Valproic Acid
2. Drug: Temozolomide + Chloroquine

MeSH:Glioblastoma Glioma Astrocytoma Neoplasms, Neuroepithelial

HPO:Astrocytoma Glioblastoma multiforme Glioma Neuroepithelial neoplasm Subependymal giant-cell astrocytoma

International Cooperative Phase III Trial of the HIT-HGG Study Group (HIT-HGG-2013) The HIT-HGG-2013 trial offers an innovative high-quality diagnostics and science program for children and adolescents >3 years, suffering from one of the following types of high grade gliomas: 1. glioblastoma WHO grade IV (GBM) 2. diffuse midlineglioma histone 3 K27M mutated WHO grade IV (DMG) 3. anaplastic astrocytoma WHO grade III (AA) 4. diffuse intrinsic pontine glioma (DIPG) 5. gliomatosis cerebri (GC) For 1.-3. --- K27M ---

immune deficiency syndrome; known tumour predisposition syndromes which do not affect adequate performance of the trial represent no exclusion criterion a priori - Known HIV positivity - Severe manifest hepatic disease including hepatic porphyria as well as personal or family history of severe hepatic dysfunction, especially drug-related - Severe pancreatic disease - Severe hepatic disease - Lethal hepatic dysfunction in a sibling during valproic acid treatment - Known urea cycle defect - Severe coagulation disorders (in regards to thrombopenia see prerequisite for blood cell count before starting treatment) - Retinopathy and restricted visual fields (Exception: Brain tumour-related changes of visual fields) - Glucose-6-phosphate dehydrogenase deficiency (favism) - Myasthenia gravis - Known porphyria - Valproic acid as antiepileptc drug for any pre-existing epilepsy - Chloroquine or hydroxycloroquine as pre-existing and ongoing medication for malaria, lupus erythematodes, or any other medical reason Glioblastoma WHO Grade IV Diffuse Midline Glioma Histone 3 K27M WHO Grade IV Anaplastic Astrocytoma WHO Grade III Diffuse Intrinsic Pontine Glioma Gliomatosis Cerebri Glioblastoma Glioma Astrocytoma Neoplasms, Neuroepithelial Indication: First-line treatment of high grade gliomas, diffuse intrinsic pontine glioma, and gliomatosis cerebri in paediatric patients < 18 years of age. --- K27M ---

The primary objective of this phase II trial is to determine the efficacy and safety of ONC201, an oral small molecule imipridone DRD2 antagonist, in adult subjects with recurrent high-grade glioma. This study will test the research hypothesis that histone H3 K27M mutation sensitizes to oral administration of ONC201 in gliomas.

NCT03295396

Conditions

1. Glioma

Interventions

1. Drug: ONC201

MeSH:Glioma

HPO:Glioma

ONC201 in Adults With Recurrent H3 K27M-mutant Glioma The primary objective of this phase II trial is to determine the efficacy and safety of ONC201, an oral small molecule imipridone DRD2 antagonist, in adult subjects with recurrent high-grade glioma. --- K27M ---

This study will test the research hypothesis that histone H3 K27M mutation sensitizes to oral administration of ONC201 in gliomas. --- K27M ---

Inclusion Criteria: 1. Histologically confirmed diagnosis of high-grade glioma (HGG) in any tumor sample and presence of histone H3 K27M mutation detected in a Clinical Laboratory Improvement Amendment (CLIA) certified laboratory by immunohistochemistry or DNA sequencing test on any glioma tumor sample. --- K27M ---

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.

NCT03416530

Conditions

1. Diffuse Intrinsic Pontine Glioma
2. Glioma, Malignant

Interventions

1. Drug: ONC201

MeSH:Glioma

HPO:Glioma

ONC201 in Newly Diagnosed Diffuse Intrinsic Pontine Glioma and Recurrent/Refractory Pediatric H3 K27M Gliomas. --- K27M ---

ONC201 in Pediatric H3 K27M Gliomas 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. --- K27M ---

ONC201 in Pediatric H3 K27M Gliomas 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. --- K27M --- --- K27M ---

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. --- K27M ---

Arm D will determine H3 K27M DNA levels and drug concentrations in the CSF of pediatric H3 K27M-mutant glioma patients. --- K27M ---

Arm D will determine H3 K27M DNA levels and drug concentrations in the CSF of pediatric H3 K27M-mutant glioma patients. --- K27M --- --- K27M ---

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. --- K27M ---

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. --- K27M ---

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. --- K27M ---

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. --- K27M ---

Post-mortem biopsy is required if H3 K27M status of tumor is unknown and archival tumor tissue not available. --- K27M ---

Post-mortem biopsy is required if H3 K27M status of tumor is unknown and archival tumor tissue not available. --- K27M ---

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. --- K27M ---

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. --- K27M ---

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. --- K27M ---

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. --- K27M ---

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. --- K27M ---

Subjects in Arm C do not require prior tumor biopsy or confirmation of the presence of the H3 K27M mutation. --- K27M ---

Subjects in Arm D must have confirmation of the presence of the H3 K27M mutation in any glioma sample prior to enrollment. --- K27M ---

Subjects in Arm F must submit at least 5 unstained slides from a tumor specimen that harbors H3 K27M mutation. --- K27M ---

Note that the H3 K27M mutation is often reported as H3 K28M in gene sequencing assays. --- K27M ---

This phase II trial studies how well veliparib, radiation therapy, and temozolomide work in treating patients with newly diagnosed malignant glioma without H3 K27M or BRAFV600 mutations. Poly adenosine diphosphate (ADP) ribose polymerases (PARPs) are proteins that help repair DNA mutations. PARP inhibitors, such as veliparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving veliparib, radiation therapy, and temozolomide may work better in treating patients with newly diagnosed malignant glioma without H3 K27M or BRAFV600 mutations compared to radiation therapy and temozolomide alone.

NCT03581292

Conditions

1. Anaplastic Astrocytoma
2. Glioblastoma
3. Malignant Glioma

Interventions

1. Radiation: Radiation Therapy
2. Drug: Temozolomide
3. Drug: Veliparib

MeSH:Glioblastoma Glioma Astrocytoma

HPO:Astrocytoma Glioblastoma multiforme Glioma Subependymal giant-cell astrocytoma

A Phase 2 Study of Veliparib (ABT-888) and Local Irradiation, Followed by Maintenance Veliparib and Temozolomide, in Patients With Newly Diagnosed High-Grade Glioma (HGG) Without H3 K27M or BRAFV600 Mutations. --- K27M ---

Veliparib, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed Malignant Glioma Without H3 K27M or BRAFV600 Mutations This phase II trial studies how well veliparib, radiation therapy, and temozolomide work in treating patients with newly diagnosed malignant glioma without H3 K27M or BRAFV600 mutations. --- K27M ---

Veliparib, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed Malignant Glioma Without H3 K27M or BRAFV600 Mutations This phase II trial studies how well veliparib, radiation therapy, and temozolomide work in treating patients with newly diagnosed malignant glioma without H3 K27M or BRAFV600 mutations. --- K27M --- --- K27M ---

Giving veliparib, radiation therapy, and temozolomide may work better in treating patients with newly diagnosed malignant glioma without H3 K27M or BRAFV600 mutations compared to radiation therapy and temozolomide alone. --- K27M ---

For analyses exploring associations of a large number of potential markers with clinical outcome, will utilize false discovery rate approaches in order to control family-wise error rate.. Inclusion Criteria: - Stratum 1 (IDH wild-type): Patients must be >= 3 years of age and =< 21 years of age at the time of enrollment - Stratum 2 (IDH mutant): Patients must be >= 3 years of age and =< 25 years of age at the time of enrollment - Patients must have eligibility confirmed by rapid central pathology and central molecular screening reviews performed on APEC14B1: - Newly-diagnosed high-grade glioma such as anaplastic astrocytoma or glioblastoma - Negative results for H3 K27M by immunohistochemistry (IHC) - Negative results for BRAFV600 mutation by next-generation sequencing (NGS) - Patients must have histological verification of diagnosis. --- K27M ---

If lumbar CSF cytology is positive, the patient is considered to have M+ disease and is ineligible - Note: False positive cytology can occur within 10 days of surgery - Patients with gliomatosis cerebri type 1 or 2 - Patients who are not able to receive protocol specified radiation therapy - Patients must not be currently receiving other anti-cancer agents - Patients with known constitutional mismatch repair deficiency syndrome (CMMR-D)/biallelic mismatch repair deficiency (bMMRD) - Female patients who are pregnant are ineligible due to risks of fetal and teratogenic adverse events as seen in animal/human studies - Lactating females are not eligible unless they have agreed not to breastfeed their infants - Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained - Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation and for 6 months after the last dose of protocol-specified chemotherapy Inclusion Criteria: - Stratum 1 (IDH wild-type): Patients must be >= 3 years of age and =< 21 years of age at the time of enrollment - Stratum 2 (IDH mutant): Patients must be >= 3 years of age and =< 25 years of age at the time of enrollment - Patients must have eligibility confirmed by rapid central pathology and central molecular screening reviews performed on APEC14B1: - Newly-diagnosed high-grade glioma such as anaplastic astrocytoma or glioblastoma - Negative results for H3 K27M by immunohistochemistry (IHC) - Negative results for BRAFV600 mutation by next-generation sequencing (NGS) - Patients must have histological verification of diagnosis. --- K27M ---

If lumbar CSF cytology is positive, the patient is considered to have M+ disease and is ineligible - Note: False positive cytology can occur within 10 days of surgery - Patients with gliomatosis cerebri type 1 or 2 - Patients who are not able to receive protocol specified radiation therapy - Patients must not be currently receiving other anti-cancer agents - Patients with known constitutional mismatch repair deficiency syndrome (CMMR-D)/biallelic mismatch repair deficiency (bMMRD) - Female patients who are pregnant are ineligible due to risks of fetal and teratogenic adverse events as seen in animal/human studies - Lactating females are not eligible unless they have agreed not to breastfeed their infants - Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained - Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation and for 6 months after the last dose of protocol-specified chemotherapy Anaplastic Astrocytoma Glioblastoma Malignant Glioma Glioblastoma Glioma Astrocytoma PRIMARY OBJECTIVES: I. To determine whether veliparib (ABT-888), when added to radiotherapy (RT) and temozolomide, is efficacious for the treatment of patients with newly-diagnosed high-grade glioma (HGG) whose tumors' molecular profile are wild-type for H3 K27M, BRAF, and IDH1/2. --- K27M ---

To determine whether veliparib (ABT-888), when added to RT and temozolomide, is efficacious for the treatment of patients with newly-diagnosed HGG whose tumors' molecular profile are wild-type for H3 K27M and BRAF and harbor an IDH1/2 mutation. --- K27M ---

This phase 2 trial will evaluate the activity of Panobinostat in combination with Everolimus for children with gliomas harboring H3.1 or H3.3K27M mutation, including newly diagnosed high-grade glioma or DIPG (diffuse intrinsic pontine glioma) after radiation (stratum A) and recurrent/progressive glioma (grade II-IV, including DIPG) (stratum B).

NCT03632317

Conditions

1. Glioma
2. Diffuse Intrinsic Pontine Glioma

Interventions

1. Drug: Panobinostat
2. Drug: Everolimus

MeSH:Glioma

HPO:Glioma

A Phase 2 Study of Panobinostat in Combination With Everolimus for Children and Young Adults With Gliomas Harboring H3.3 or H3.1 K27M Mutation. --- K27M ---

- H3K27M mutation: Participants must have a mutation in H3.3 K27M or H3.1 K27M as identified by tumor (FFPE or fresh, diagnosis or relapse tissue, but relapse tissue preferred) sequencing, or by CLIA-certified immunohistochemistry staining positive for H3K27M, as defined by review by U of M neuro-pathology. --- K27M ---

- H3K27M mutation: Participants must have a mutation in H3.3 K27M or H3.1 K27M as identified by tumor (FFPE or fresh, diagnosis or relapse tissue, but relapse tissue preferred) sequencing, or by CLIA-certified immunohistochemistry staining positive for H3K27M, as defined by review by U of M neuro-pathology. --- K27M --- --- K27M ---

Pediatric high-grade gliomas are highly aggressive and treatment options are limited. The purpose of this first-in-pediatrics study is to examine the safety, tolerability, and pharmacokinetics of GDC-0084 and to estimate its maximum tolerated dose (MTD) when administered to pediatric patients with diffuse intrinsic pontine glioma (DIPG) or other diffuse midline H3 K27M-mutant gliomas after they have received radiation therapy (RT). GDC-0084 is a brain-penetrant inhibitor of a growth-promoting cell signaling pathway that is dysregulated in the majority of diffuse midline glioma tumor cells. This study is also designed to enable a preliminary assessment of the antitumor activity of single-agent GDC-0084, in the hope of enabling rational combination therapy with systemic therapy and/or radiation therapy (RT) in this patient population, which is in desperate need of therapeutic advances. Primary Objectives 1. To estimate the maximum tolerated dose (MTD) and/or the recommended phase 2 dosage (RP2D) of GDC-0084 in pediatric patients with newly diagnosed diffuse midline glioma, including diffuse intrinsic pontine glioma (DIPG) 2. To define and describe the toxicities associated with administering GDC-0084 after radiation therapy (RT) in a pediatric population 3. To characterize the pharmacokinetics of GDC-0084 in a pediatric population Secondary Objectives 1. To estimate the rate and duration of radiographic response in patients with newly diagnosed DIPG or other diffuse midline glioma treated with RT followed by GDC-0084 2. To estimate the progression-free survival (PFS) and overall survival (OS) distributions for patients with newly diagnosed DIPG or other diffuse midline glioma treated with RT followed by GDC-0084

NCT03696355

Conditions

1. Brain and Central Nervous System Tumors

Interventions

1. Drug: GDC-0084
2. Radiation: radiation therapy

MeSH:Glioma Nervous System Neoplasms Central Nervous System Neoplasms

HPO:Glioma Neoplasm of the central nervous system Neoplasm of the nervous system

The purpose of this first-in-pediatrics study is to examine the safety, tolerability, and pharmacokinetics of GDC-0084 and to estimate its maximum tolerated dose (MTD) when administered to pediatric patients with diffuse intrinsic pontine glioma (DIPG) or other diffuse midline H3 K27M-mutant gliomas after they have received radiation therapy (RT). --- K27M ---

- Biopsied typical DIPG: WHO grade II diffuse astrocytoma (IDH WT or IDH NOS), WHO grade III anaplastic astrocytoma (IDH WT or IDH NOS), WHO grade IV glioblastoma (IDH WT or IDH NOS), or diffuse midline glioma, H3 K27M mutant. --- K27M ---

Subjects with a typical DIPG who undergo a biopsy may be eligible for the study if the tumor does not harbor the H3 K27M mutation, yet eligibility is restricted to diffuse astrocytoma, anaplastic astrocytoma or glioblastoma, IDH WT or IDH NOS, tumors. --- K27M ---

- Atypical brainstem glioma: diffuse midline glioma, H3 K27M mutant. --- K27M ---

- Non-brainstem midline glioma, defined as tumors with an epicenter within midline structures, including the thalamus, spinal cord, and cerebellum: diffuse midline glioma, H3 K27M mutant. --- K27M ---

This phase II trial studies how well the combination of dabrafenib and trametinib works after radiation therapy in children and young adults with high grade glioma who have a genetic change called BRAF V600 mutation. Radiation therapy uses high energy rays to kill tumor cells and reduce the size of tumors. Dabrafenib and trametinib may stop the growth of tumor cells by blocking BRAF and MEK, respectively, which are enzymes that tumor cells need for their growth. Giving dabrafenib with trametinib after radiation therapy may work better than treatments used in the past in patients with newly-diagnosed BRAF V600-mutant high-grade glioma.

NCT03919071

Conditions

1. Anaplastic Astrocytoma
2. Anaplastic Ganglioglioma
3. Anaplastic Pleomorphic Xanthoastrocytoma
4. Glioblastoma
5. Malignant Glioma
6. WHO Grade III Glioma

Interventions

1. Drug: Dabrafenib Mesylate
2. Radiation: Radiation Therapy
3. Drug: Trametinib Dimethyl Sulfoxide

MeSH:Glioblastoma Glioma Astrocytoma Ganglioglioma

HPO:Astrocytoma Glioblastoma multiforme Glioma Subependymal giant-cell astrocytoma

- Patients must be >= 3 years and =< 21 years of age at the time of enrollment - Patients must have eligibility confirmed by Rapid Central Pathology and Molecular Screening Reviews performed on APEC14B1 - Newly diagnosed high-grade glioma with BRAFV600-mutation - Negative results for H3 K27M by immunohistochemistry (IHC) - Histologically confirmed high-grade glioma (World Health Organization [WHO] grade III or IV) including but not limited to: anaplastic astrocytoma (AA), anaplastic pleomorphic xanthoastrocytoma (aPXA), anaplastic gangliogliomas (aGG), glioblastoma (GB), and high-grade astrocytoma, not otherwise specified (NOS) - Patients must have had histologic verification of a high-grade glioma diagnosis. --- K27M ---

Anaplastic Astrocytoma Anaplastic Ganglioglioma Anaplastic Pleomorphic Xanthoastrocytoma Glioblastoma Malignant Glioma WHO Grade III Glioma Glioblastoma Glioma Astrocytoma Ganglioglioma PRIMARY OBJECTIVE: I. To estimate the event-free survival (EFS) distribution for newly-diagnosed patients with BRAFV600-mutant high-grade glioma (HGG) without H3 K27M mutations excluding anaplastic pleomorphic xanthoastrocytoma (aPXA) and anaplastic ganglioglioma (aGG) treated with radiation therapy followed by a maintenance combination of dabrafenib mesylate (dabrafenib) and trametinib dimethyl sulfoxide (trametinib) and to compare this EFS to contemporary historical controls. --- K27M ---

SECONDARY OBJECTIVES: I. To describe the overall survival (OS) distribution for newly-diagnosed patients with BRAFV600-mutant HGG without H3 K27M mutations excluding aPXA and aGG treated with radiation therapy followed by a maintenance combination of dabrafenib and trametinib. --- K27M ---

To describe the EFS and overall survival (OS) distribution for newly-diagnosed patients with BRAFV600E-mutant aPXA and aGG without H3 K27M mutations treated with radiation therapy followed by a maintenance combination of dabrafenib and trametinib. --- K27M ---

The primary purpose of this study is to test whether GD2-CAR T cells can be successfully made from immune cells collected from children and young adults with H3K27M-mutant diffuse intrinsic pontine glioma (DIPG) or spinal H3K27M-mutant diffuse midline glioma (DMG). H3K27Mmutant testing will occur as part of standard of care prior to enrollment.

NCT04196413

Conditions

1. Glioma of Spinal Cord
2. Glioma of Brainstem

Interventions

1. Drug: GD2 CAR T cells
2. Drug: Fludarabine
3. Drug: Cyclophosphamide

MeSH:Glioma

HPO:Glioma

Severity of dose limiting toxicities (DLTs) following chemotherapy and infusion of GD2CART cells, will be recorded and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 at each dose level tested in subjects with H3K27M-mutant DIPG following standard upfront radiation therapy.. Safety of GD2CART in subjects with spinal H3 K27M-mutant DMG treated at the RP2D. --- K27M ---

Crohns, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years Glioma of Spinal Cord Glioma of Brainstem Glioma Primary Objectives: - Determine the feasibility of manufacturing autologous T cells transduced with 14g2a-CD8-BBz-iCasp9 retroviral vector expressing GD2 Chimeric Antigen Receptor (GD2CART) for administration in subjects with H3K27M+ diffuse intrinsic pontine glioma (DIPG) or subjects with spinal H3 K27M-mutant diffuse midline glioma (DMG) using a retroviral vector and dasatinib in the Miltenyi CliniMACS Prodigy® system. --- K27M ---

Secondary Objectives: - In a preliminary manner, assess clinical benefit of GD2CART at the RP2D in subjects with H3K27M DIPG or spinal H3 K27M-mutant DMG. - If unacceptable toxicity occurs that is possibly, probably or likely related to GD2CART, assess the capacity for AP1903, a dimerizing agent, to mediate clearance of the genetically engineered cells and resolve toxicity. --- K27M ---

This phase I trial studies the side effects and best dose of trametinib and everolimus in treating pediatric and young adult patients with low grade gliomas that has come back (recurrent). Trametinib acts by targeting a protein in cells called MEK and disrupting tumor growth. Everolimus is a drug that may block another pathway in tumor cells that can help tumors grow. Giving trametinib and everolimus may work better to treat low grade gliomas compared to trametinib or everolimus alone.

NCT04485559

Conditions

1. Recurrent World Health Organization (WHO) Grade II Glioma

Interventions

1. Drug: Everolimus
2. Drug: Trametinib

MeSH:Glioma

HPO:Glioma

Trametinib and everolimus pharmacokinetics after single dose will be compared to trametinib and everolimus pharmacokinetics after repeated doses.. Inclusion Criteria: - Subjects must have histologically confirmed diagnosis of a LGG (World Health Organization [WHO] grade I-II) that is recurrent or progressive after prior treatment (biologic, chemotherapy or radiation therapy) - Patients who have had surgery alone are not eligible - Patients with neurofibromatosis type 1 (NF1) are eligible but must have available tissue per study requirements NF status will be collected - Patients with spinal cord primaries or disseminated disease are eligible - Patients with a known K27M mutation are considered by current WHO as grade IV and are ineligible for this study - For enrollment, snap frozen tissue (150 mg) or 10 unstained 10 um formalin-fixed, paraffin-embedded (FFPE) slides for comprehensive genomic testing or results of prior testing is required - If clinical comprehensive testing has already been performed, the requirement for submission of tissue may be waived after discussion and review of results with study chairs - Patients must have evaluable disease - Prior therapy: Patients must have received prior therapy other than surgery and must have fully recovered from the acute toxic effects of all prior chemotherapy, biologics, immunotherapy, or radiotherapy prior to entering this study - Myelosuppressive chemotherapy: Patients must have received their last dose of known myelosuppressive anticancer chemotherapy at least three weeks prior to study registration or at least six weeks if they had received nitrosourea. --- K27M ---

If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required - Human immunodeficiency virus (HIV) positive patients will be ineligible if HIV therapy regimen has not been stable for at least 4 weeks or there is intent to change the regimen within 8 weeks following enrollment, or if they are severely immunocompromised - Patients with known hepatitis B or C are not eligible - Patients with any clinically significant unrelated systemic illness (serious infectious or significant cardiac, pulmonary, hepatic or other organ dysfunction), which in the opinion of the investigator would interfere with the study procedures or results - Patients with other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) including heart failure that meets New York Heart Association (NYHA) class II or above are excluded Inclusion Criteria: - Subjects must have histologically confirmed diagnosis of a LGG (World Health Organization [WHO] grade I-II) that is recurrent or progressive after prior treatment (biologic, chemotherapy or radiation therapy) - Patients who have had surgery alone are not eligible - Patients with neurofibromatosis type 1 (NF1) are eligible but must have available tissue per study requirements NF status will be collected - Patients with spinal cord primaries or disseminated disease are eligible - Patients with a known K27M mutation are considered by current WHO as grade IV and are ineligible for this study - For enrollment, snap frozen tissue (150 mg) or 10 unstained 10 um formalin-fixed, paraffin-embedded (FFPE) slides for comprehensive genomic testing or results of prior testing is required - If clinical comprehensive testing has already been performed, the requirement for submission of tissue may be waived after discussion and review of results with study chairs - Patients must have evaluable disease - Prior therapy: Patients must have received prior therapy other than surgery and must have fully recovered from the acute toxic effects of all prior chemotherapy, biologics, immunotherapy, or radiotherapy prior to entering this study - Myelosuppressive chemotherapy: Patients must have received their last dose of known myelosuppressive anticancer chemotherapy at least three weeks prior to study registration or at least six weeks if they had received nitrosourea. --- K27M ---

The primary objective of this phase 1 trial is to determine the maximum tolerated dose (MTD), food effect, safety and tolerability of oral ONC206 in patients with recurrent, primary CNS neoplasms.

NCT04541082

Conditions

1. Central Nervous System Neoplasms
2. Glioblastoma
3. Gliosarcoma, Adult
4. Anaplastic Oligodendroglioma
5. Anaplastic Astrocytoma
6. Pilocytic Astrocytoma
7. Oligodendroglioma
8. Gliomatosis Cerebri
9. Pleomorphic Xanthoastrocytoma
10. Anaplastic Pleomorphic Xanthoastrocytoma
11. Diffuse Midline Glioma, H3 K27M-Mutant
12. Ependymoma
13. Ependymoma, Anaplastic
14. Medulloblastoma
15. Teratoid Rhabdoid Tumor
16. Neuroectodermal Tumors, Primitive
17. Neuroectodermal Tumors
18. Anaplastic Meningioma
19. Atypical Meningioma
20. Choroid Plexus Neoplasms
21. Pineal Tumor
22. Diffuse Astrocytoma
23. Glial Tumor

Interventions

1. Drug: ONC206

MeSH:Neoplasms Glioblastoma Astrocytoma Ependymoma Gliosarcoma Meningioma Oligodendroglioma Medulloblastoma Neuroectodermal Tumors Neuroectodermal Tumors, Primitive Rhabdoid Tumor Nervous System Neoplasms Central Nervous System Neoplasms Neoplasms, Neuroepithelial Pinealoma Choroid Plexus Neoplasms

HPO:Astrocytoma Ependymoblastoma Ependymoma Glioblastoma multiforme Intracranial meningioma Medulloblastoma Medulloepithelioma Meningioma Neoplasm Neoplasm of the central nervous system Neoplasm of the nervous system Neuroectodermal neoplasm Neuroepithelial neoplasm Pineal parenchymal cell neoplasm Pinealoma Pineoblastoma Pineocytoma Primitive neuroectodermal tumor Spinal meningioma Subependymal giant-cell astrocytoma Supratentorial neoplasm

Central Nervous System Neoplasms Glioblastoma Gliosarcoma, Adult Anaplastic Oligodendroglioma Anaplastic Astrocytoma Pilocytic Astrocytoma Oligodendroglioma Gliomatosis Cerebri Pleomorphic Xanthoastrocytoma Anaplastic Pleomorphic Xanthoastrocytoma Diffuse Midline Glioma, H3 K27M-Mutant Ependymoma Ependymoma, Anaplastic Medulloblastoma Teratoid Rhabdoid Tumor Neuroectodermal Tumors, Primitive Neuroectodermal Tumors Anaplastic Meningioma Atypical Meningioma Choroid Plexus Neoplasms Pineal Tumor Diffuse Astrocytoma Glial Tumor Neoplasms Glioblastoma Astrocytoma Ependymoma Gliosarcoma Meningioma Oligodendroglioma Medulloblastoma Neuroectodermal Tumors Neuroectodermal Tumors, Primitive Rhabdoid Tumor Nervous System Neoplasms Central Nervous System Neoplasms Neoplasms, Neuroepithelial Pinealoma Choroid Plexus Neoplasms null --- K27M ---

This is an intermediate-size expanded access protocol to provide ONC201 to patients with H3 K27M-mutant and/or midline gliomas who cannot access ONC201 through clinical trials.

NCT04617002

Conditions

1. Glioma
2. H3 K27M

Interventions

1. Drug: ONC201

MeSH:Glioma

HPO:Glioma

Intermediate-size Expanded Access to ONC201 for Patients With H3 K27M-mutant and/or Midline Gliomas. --- K27M ---

Intermediate-size Expanded Access to ONC201 for Patients With H3 K27M-mutant and/or Midline Gliomas This is an intermediate-size expanded access protocol to provide ONC201 to patients with H3 K27M-mutant and/or midline gliomas who cannot access ONC201 through clinical trials. --- K27M ---

Intermediate-size Expanded Access to ONC201 for Patients With H3 K27M-mutant and/or Midline Gliomas This is an intermediate-size expanded access protocol to provide ONC201 to patients with H3 K27M-mutant and/or midline gliomas who cannot access ONC201 through clinical trials. --- K27M --- --- K27M ---

Inclusion Criteria: 1. Patient meet one or more of the criteria below: Arm A 1. Central nervous system tumor that is positive for the H3 K27M mutation (performed in a laboratory with CLIA or equivalent certification); 2. Central nervous system tumor involving the thalamus, hypothalamus, basal ganglia, brainstem, cerebellum, cerebellar peduncle, midline cortex, corpus callosum, pineal region, optic tract, or optic chiasm. --- K27M ---

H3 K27M status does not have to be known or positive for this arm. --- K27M ---

7. A history of Torsades de Pointes or heart failure, hypokalemia, or family history of prolonged QT Syndrome 8. Concomitant use of medication(s) known to prolong the QT/QTc interval Inclusion Criteria: 1. Patient meet one or more of the criteria below: Arm A 1. Central nervous system tumor that is positive for the H3 K27M mutation (performed in a laboratory with CLIA or equivalent certification); 2. Central nervous system tumor involving the thalamus, hypothalamus, basal ganglia, brainstem, cerebellum, cerebellar peduncle, midline cortex, corpus callosum, pineal region, optic tract, or optic chiasm. --- K27M ---

7. A history of Torsades de Pointes or heart failure, hypokalemia, or family history of prolonged QT Syndrome 8. Concomitant use of medication(s) known to prolong the QT/QTc interval Glioma H3 K27M Glioma null --- K27M ---