Histologically confirmed oligodendroglioma or mixed glioma
Newly diagnosed and =< 3 months from surgical diagnosis; patients are also eligible if they have had a prior surgical procedure > 3 months earlier for low grade glioma, as long as the patient has not received prior radiation or prior chemotherapy
Histological evidence of World Health Organization (WHO) grade III anaplastic glioma or WHO grade II low grade glioma with locally diagnosed combined 1p/19q loss and the presence of an either IDH1 or IDH2, both as established by a local or referenced laboratory qualified for the study\r\n* Note: mixed gliomas are eligible, regardless of the degree of astrocytic or oligodendrocytic predominance, as long as the tumor is also co-deleted for 1p and 19q
History of prior radiation therapy or chemotherapy for glioma; note: patients who have a history of prior low grade glioma (with or without a distant history of prior surgery for that glioma), but who have never received prior chemotherapy or radiation therapy for the glioma are eligible for the study
Patients with a histologically confirmed diagnosis of high-grade glioma (HGG), medulloblastoma, CNS embryonal tumor (not otherwise specified [NOS]), ependymoma, or atypical teratoid rhabdoid tumor (ATRT) that is recurrent, progressive or refractory
Patients with recurrent diffuse intrinsic pontine glioma (DIPG) with typical radiographic appearance who have undergone biopsy are eligible provided there is histologic confirmation of malignant glioma World Health Organization (WHO) II-IV; Rb1 screening for these patients is required only if adequate tissue is available
Radiographically-confirmed progression of, or recurrent, primary or secondary Grade IV glioma, and must be on a stable or decreasing dose of steroid for at least five days prior to the date of informed consent.
The size of the Grade IV glioma tumor is multi-focal and > 30mm in size, as assessed at the baseline (pre-study) MRI evaluation.
Diagnosis of DIPG or high-grade glioma originating from the brain stem
Patients with biopsy proven low grade glioma or astrocytoma, ependymoma, craniopharyngioma, meningioma, neurocytoma, medulloblastoma or gangliogliomas or other rare tumor requiring tumor bed or tumor irradiation; patients with a presumed diagnosis of optic glioma or gliomas based on imaging and clinical characteristics will also be allowed on this trial as it may be against the standard of care to biopsy some of these individuals (for example, a patient with neurofibromatosis [NF]-1 and an optic glioma will not require a biopsy for diagnosis)
Patients with biopsy proven high-grade glioma (excluding glioblastoma multiforme [GBM]) and a gross total resection and patients with non-disseminated atypical teratoid rhabdoid (ATRT) patients may also be included
All patients must have radiographically progressive low-grade glioma (including NF1 related visual pathway gliomas) after failure of a carboplatin-containing regimen; patients do not require a biopsy to confirm the diagnosis
A patient with low grade glioma who has failed standard therapy
At the time of surgery, frozen biopsy confirmation of high grade or malignant glioma by neuropathologist; biopsy confirmation of glioma or infiltrative glioma at time of surgery will be acceptable, provided that subject has prior pathology confirmation of high-grade glioma; if subject had previous diagnosis of low grade glioma, then the biopsy must show high grade glioma\r\n* To be confirmed at time of surgery, after registration in OnCore
Patients must have refractory, progressive or recurrent confirmed low-grade glioma (World Health Organization [WHO] grade I or II) that was confirmed histologically at initial diagnosis
Low grade glioma NOS
Histologically proven diagnosis of high-grade glioma, including anaplastic glioma (WHO grade III with 1p/19q chromosomes intact), glioblastoma (WHO grade IV) or gliosarcoma (WHO Grade IV);
Presence of T1 gadolinium (Gd) –enhancing lesions (on MRI) suggestive of high-grade glioma
Stratum A, currently closed to enrollment: Patients must have a recurrent, progressive or refractory DIPG following radiation therapy with or without chemotherapy\r\n* Histologic diagnosis is not required for patients with typical imaging findings of DIPG (defined as patients with a diffuse expansile mass centered in and involving at least 2/3 of the pons); patients with brainstem tumors who have undergone biopsy with a diagnosis of high-grade glioma or diffuse infiltrating glioma are also eligible
Stratum B: Patients must have a histologically confirmed diagnosis of a non-brainstem high-grade glioma (NB-HGG) that is recurrent, progressive or refractory following therapy which included radiotherapy; spinal primary disease is eligible
EXCLUSION CRITERIA FOR STRATUM C: Patients with diffuse intrinsic pontine or other brainstem high-grade glioma and those with primary spinal cord tumors
There must be an interval of at least 12 weeks from the completion of standard front line therapy to study registration unless there is unequivocal evidence for tumor recurrence per RANO criteria; when the interval is less than 12 weeks, the use of perfusion imaging and/or positron emission tomography (PET) scan is allowed to differentiate between unequivocal evidence of tumor recurrence and pseudo-progression; standard front line therapy is as described below:\r\n* For grade IV malignant gliomas (GBM): standard front line therapy for newly diagnosed GBM must include maximal feasible surgical resection (biopsy alone allowed), radiotherapy, and temozolomide chemotherapy; if the tumor was initially diagnosed as either a grade II or III tumor and now has recurred or progressed as a grade IV GBM, it will be considered a secondary recurrent grade IV GBM and will be eligible for this study as long as prior treatment included maximal feasible surgical resection (biopsy alone allowed), radiotherapy, and temozolomide chemotherapy\r\n* For grade III malignant gliomas with 1p 19q codeletions: standard front line therapy for newly diagnosed grade III malignant gliomas must include maximal feasible surgical resection (biopsy alone allowed), radiotherapy, and chemotherapy (procarbazine, lomustine, and vincristine sulfate [PCV] or temozolomide); if the patient did not receive any or all components of the standard front line therapy as detailed above for newly diagnosed grade III gliomas with 1p 19q codeletions and the tumor then recurred or progressed, s/he must first receive at least one prior standard therapy or any appropriate combination of the components of standard therapy as detailed above and must experience further recurrence or progression before s/he is deemed eligible for this study; if the tumor was initially diagnosed as a grade II glioma with 1p 19q codeletions and now has recurred or progressed as a grade III tumor, it will be considered a secondary recurrent grade III glioma with 1p 19q codeletions and will be eligible for this study as long as prior treatment included maximal feasible surgical resection (biopsy alone allowed), radiotherapy, and chemotherapy (PCV or temozolomide)\r\n* For grade III malignant glioma without 1p 19q codeletions: standard front line therapy for newly diagnosed grade III malignant gliomas must include maximal feasible surgical resection (biopsy alone allowed), radiotherapy, and temozolomide chemotherapy; if the tumor was initially diagnosed as a grade II glioma without 1p 19q codeletions and now has recurred or progressed as a grade III tumor, it will be considered a secondary recurrent grade III glioma without 1p 19q codeletions and will be eligible for this study as long as prior treatment included maximal feasible surgical resection (biopsy alone allowed), radiotherapy, and temozolomide chemotherapy
Participants with a diagnosis of recurrent, progressive, or refractory low grade glioma (LGG)
STRATUM B: Participants with low grade glioma (LGG) or diffuse intrinsic pontine glioma (DIPG)
Participant has a prior histologically-confirmed diagnosis of a grade III or IV glioma, or has a prior histologically-confirmed diagnosis of a grade II glioma and now has radiographic progression consistent with a grade III or IV malignant glioma (MG)
NF-1 patients with radiographic evidence of a progressive, recurrent or refractory low grade glioma, with or without pre-treatment tumor tissue
STRATUM A: Histological confirmation of a newly diagnosed high-grade glioma or DIPG
STRATUM B: Histological confirmation (at diagnosis or relapse) of a recurrent or progressive grade II-IV glioma (including DIPG)
Histopathologically proven previous diagnosis of medulloblastoma or grade III or IV glioma
Patients must have received no more than 3 prior therapies for recurrent high grade glioma (rHGG)
Subject has a diagnosis of high-grade glioma, medulloblastoma, ependymoma or Diffuse intrinsic pontine glioma (DIPG) that is recurrent or progressive. Subjects with neurofibromatosis type 1 (NF-1) associated tumors are eligible if the meet all other eligibility criteria.
Subject has any prior history of malignancies, other than high-grade glioma, medulloblastoma, ependymoma or DIPG (Note: radiation-associated gliomas are excluded from enrollment)
Patients must have histologically confirmed low or high grade glioma (grade II-IV)
Histologically confirmed or radiographic evidence of recurrent/progressive high-grade glioma after treatment with bevacizumab
Histopathologically proven diagnosis of ependymoma, medulloblastoma, pineoblastoma/pineocytoma, choroid plexus carcinoma/papilloma, chordoma, gliomatosis cerebri, brainstem glioma, midline glioma, ATRT, atypical/malignant meningioma, gliosarcoma or primary brain sarcoma prior to registration as confirmed by National Cancer Institute (NCI) Laboratory of Pathology
Patients must have a presumed newly identified high grade glioma based on clinical and radiologic evaluation; pathologic confirmation of high grade glioma must be made at the time of stereotactic biopsy or resection on frozen section by a neuropathologist prior to NSC-CRAd-S-pk7 injection; if this is not possible, the injection will not be performed and the subject will no longer be eligible for the study
Evidence of an active optic glioma or other low-grade glioma, requiring treatment with chemotherapy or radiation therapy; patients not requiring treatment are eligible for this protocol
Be at first or second relapse; Note: relapse is defined as progression following initial therapy (i.e., radiation +/- chemotherapy); for participants who had prior therapy for a low-grade glioma, the surgical diagnosis of a high-grade glioma will be considered the first relapse
Patients must have a recurrent supratentorial WHO grade IV malignant glioma based on imaging studies with measurable disease (>= 1 cm and =< 5.5 cm of contrast-enhancing tumor); prior histopathology consistent with a World Health Organization (WHO) grade IV malignant glioma confirmed by the study pathologist, Roger McLendon, or his designate
Recurrent or multifocal high grade glioma (HGG)
Patients must have pathologically proven diagnosis of high grade glioma
Recurrent glioma, or tumor involving the brainstem or cerebellum; prior low-grade glioma without prior RT, now with malignant progression are eligible
Patients with recurrent diffuse intrinsic pontine glioma (DIPG)
Prior antitumor therapy for glioma (other than steroids)
Subjects must be within 12 weeks of last major neurosurgical procedure for the high-grade glioma (craniotomy, open biopsy, or stereotactic biopsy)
Recurrent medulloblastoma or recurrent high grade glioma
Patients with low grade glioma are not eligible
Eligibility Criteria\n\n          -  Age: 3-21 years.\n\n          -  Group 1 or Group 3: histologically proven initial diagnosis of primary malignant brain\n             tumor, with no known curative treatment options.\n\n          -  Group 2: histologically proven initial diagnosis of high-grade glioma (WHO grade III\n             and IV), ependymoma, medulloblastoma, or other primary central nervous system tumor.\n\n          -  Group 3b: Patients with a radiographic diagnosis or histologically proven diagnosis of\n             diffuse intrinsic pontine glioma (DIPG).\n\n          -  MRI confirmation of tumor progression or regrowth.\n\n          -  Patients must be able to swallow whole capsules.\n\n          -  Patients with metastatic disease are eligible for enrollment.\n\n          -  Lansky or Karnofsky performance status score must be > 50%.\n\n          -  Seizure disorders must be well controlled on antiepileptic medication.\n\n          -  DIPG patients enrolled to Group 3b must not have been previously treated with\n             radiation or any medical therapy.\n\n          -  Patients previously treated with temozolomide, cyclophosphamide, and/or etoposide are\n             eligible for enrollment.\n\n        Exclusion Criteria\n\n          -  Prior invasive malignancy, other than the primary central nervous system tumor, unless\n             the patient has been disease free and off therapy for that disease for a minimum of 3\n             years\n\n          -  Patients with baseline QTc interval of more than 470 msec at study entry, and patients\n             with congenital long QTc syndrome.\n\n          -  Active autoimmune disease
Histologically confirmed diagnosis of supratentorial WHO grade III or IV glioma (high grade glioma) that has undergone surgical biopsy or resection followed by adjuvant chemoradiotherapy, that has evidence of recurrence or progression based on imaging studies and surgical resection of the enhancing tumor is clinically indicated
Recurrent high grade glioma
Patient with diagnosis of diffuse intrinsic pontine glioma
Prior bevacizumab for treatment of glioblastoma or high grade glioma
Participant has a prior histologically-confirmed diagnosis of a grade III or IV glioma, or has a prior histologically-confirmed diagnosis of a grade II glioma and now has radiographic progression consistent with a grade III or IV malignant glioma (MG) after completing standard therapy
Clinical and/or radiographic, progressive and resectable grade II glioma
High-grade glioma has recurred or progressed after prior treatment with brain radiation and temozolomide
Patients must have a previously histologically or cytologically confirmed high grade glioma (astrocytic or oligodendroglial supratentorial tumors grade 3 or 4) that has been previously treated with fractionated radiation therapy and now shows evidence of recurrence
Patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a high grade glioma is made
Histologically confirmed glioma
Pathologically confirmed high-grade glioma (World Health Organization [WHO] grade 3 or 4), with documented computed tomography (CT) or magnetic resonance imaging (MRI) progression or recurrence; biopsy is also an acceptable method of confirming progression; if initial tumor was grade 2 glioma, histological confirmation of high-grade recurrence is required\r\n* After first interim analysis, if the study proceeds to enrollment of selected patients (only those who have PDGFR alpha-positive tumors), patients will be pre-registered for PDGFR alpha analysis and registered to the combination treatment schema only if PDGFR alpha-positive and all other enrollment criteria are met
Intraoperative histological frozen section at the time of tumor resection compatible with high-grade glioma; if intraoperative diagnosis is not compatible with high grade glioma, the patient will not be treated
Infratentorial high grade glioma
Participants must have either:\r\n* Histologically confirmed low-grade gliomas as defined by, World Health Organization (WHO) classification I-II/IV; these tumors can include astrocytomas, oligodendrogliomas, and mixed variants such as oligoastrocytomas; WHO classification is not required when pathology can only confirm that glioma is low grade; Karnofsky performance status (KPS) must be >= 70 OR\r\n* Histologically confirmed favorable anaplastic glioma as defined by WHO grade III with either or both isocitrate dehydrogenase 1 (IDH1) mutation or 1p/19q codeletion; in addition, these participants must have a KPS >= 70
Subjects with histologically confirmed high-grade glioma are eligible; diagnosis of high-grade glioma will be made on the basis of needle biopsy, open biopsy, or surgical resection
Confirmed histopathology of WHO grade III glioma or WHO grade IV GBM at primary diagnosis
Recurrent glioma, or tumor involving the brainstem or cerebellum. Prior low-grade glioma without prior RT, now with malignant progression are eligible.
Malignant glioma patients within 12 weeks of completion of radiation concurrent temozolomide will be excluded
Inclusion Criteria:\n\n        For more information regarding Bristol-Myers Squibb Clinical Trial participation, please\n        visit www.BMSStudyConnect.com\n\n          -  Children and adolescents diagnosed with either:\n\n          -  Diffuse Intrinsic Pontine Glioma (DIPG), in first-line, after completion of standard\n             radiotherapy\n\n          -  High Grade Glioma (HGG), recurrent or progressive\n\n          -  Medulloblastoma, recurrent or progressive\n\n          -  Ependymoma, recurrent or progressive\n\n          -  Other high-grade tumors of the central nervous system, recurrent or progressive\n\n          -  Lansky play score (LPS) for =< 16 years of age or Karnofsky performance scale (KPS)\n             for > 16 years of age assessed within two weeks of enrollment must be >= 60\n\n          -  A tumor sample must be available for submission to central laboratory [not required\n             for DIPG]\n\n        Exclusion Criteria:\n\n          -  Participants with active, known or suspected autoimmune disease\n\n          -  Participants unable to taper steroids due to ongoing mass effect\n\n          -  Participants with low-grade gliomas or tumors of unknown malignant potential\n\n          -  Prior treatment with any drug that targets T cell co-stimulation pathways (such as\n             checkpoint inhibitors)\n\n        Other protocol defined inclusion/exclusion criteria could apply
Has more than three recurrences of high grade glioma; previous recurrences of low grade glioma is not considered
Recurrent grade 3 or 4 glioma, including astrocytoma, oligodendroglioma or mixed glioma with histologic confirmation at initial diagnosis or recurrence
Patient's high-grade glioma has recurred or progressed after prior treatment with brain radiation and temozolomide
After surgery, a pathological diagnosis of malignant glioma (WHO Grade III or IV) will need to be established
Patient must have evaluable disease by RECIST v1.1 for patients without glioma or by RANO or RANO LGG criteria for patients with glioma
Prior treatment with TMZ for low grade glioma or glioblastoma.
High-grade Glioma (HGG)
Has more than three recurrences of high grade glioma
Radiographically proven recurrent (>= first relapse), intracranial glioma
Patients must be at first or second relapse and clinically require reoperation for tumor progression within 4 to 6 weeks; Note: relapse is defined as progression following initial therapy (i.e., radiation, chemotherapy, or radiation + chemotherapy); if the participant had a surgical resection for relapsed disease and no anti-tumor therapy instituted for up to 12 weeks, this is considered one relapse; for participants who had prior therapy for a low grade glioma, the surgical diagnosis of a high grade glioma will be considered first relapse
Be at first or second relapse; Note: relapse is defined as progression following initial therapy (i.e., radiation +/- chemotherapy); if the participant had a surgical resection for relapsed disease and no antitumor therapy was instituted for up to 12 weeks, this is considered one relapse; for participants who had prior therapy for a low-grade glioma, the surgical diagnosis of a high-grade glioma will be considered the first relapse
Expansion Cohort only: Patients with high grade glioma (grade 3 and 4) that are refractory to standard therapies, and who have progressive disease following radiation therapy. Patients with any number of prior treatments are allowed.
Subjects with primary CNS malignancy other than high grade glioma (Grade 3 or 4)
Histologically confirmed diagnosis of supratentorial WHO grade III or IV glioma (high grade glioma) that has undergone surgical biopsy or resection followed by adjuvant chemoradiotherapy, that has evidence of recurrence or progression based on imaging studies and a stereotactic biopsy is indicated for confirmation of recurrence/progression
Prior radiation or chemotherapy for glioma
Patients must have received prior radiotherapy and prior temozolomide as treatment for the malignant glioma
Multiple intracranial malignant glioma lesions
Patients must have pathologically proven diagnosis of high grade glioma
Evidence of an active optic glioma or other low-grade glioma, requiring treatment with chemotherapy or radiation therapy; subjects not requiring treatment are eligible for this protocol
Subjects must have evaluable disease by RECIST v1.1 for subjects without glioma or by RANO criteria for subjects with glioma.
Dose Expansion: Non-enhancing Glioma
Subjects must have progressive glioma that is solely non-enhancing on MRI.
Progression of glioma must have occurred over 12 months or less.
Subjects with histologically confirmed Grade IV malignant glioma
Phase 2: Ewing sarcoma/peripheral primitive neuroectodermal tumor (pPNET), Rhabdomyosarcoma, High Grade Glioma (HGG) (all must have measurable disease); exclusion of Diffuse Intrinsic Pontine Glioma
Patients may have had treatment for no more than 2 prior relapses; relapse is defined as progression following initial therapy (i.e. radiation +/- chemotherapy [chemo] if that was used as initial therapy); the intent therefore is that patients had no more than 3 prior therapies (initial and treatment for 2 relapses); if the patient had a surgical resection for relapsed disease and no anti-cancer therapy was instituted for up to 12 weeks, and the patient undergoes another surgical resection, this is considered as 1 relapse; for patients who had prior therapy for a low-grade glioma, the surgical diagnosis of a high-grade glioma will be considered the first relapse
Recurrent high grade glioma
Patients must have histologically confirmed newly diagnosed high-grade glioma (World Health Organization [WHO] grade III or IV)
Pathological diagnosis for the recurrent disease demonstrate transformation to higher grade (i.e. WHO grade III or IV) gliomas, even if the initial diagnosis was WHO grade II glioma
All patients require an initial diagnosis of a malignant glioma as outlined in the inclusion criteria which must be confirmed at the treating facility
Patients must have a recurrent supratentorial WHO grade IV malignant glioma based on imaging studies with measurable disease (>= 1 cm and =< 5.5 cm of contrast-enhancing tumor); prior histopathology consistent with a World Health Organization (WHO) grade IV malignant glioma confirmed by the study pathologist, Roger McLendon, or his designate
Patients with histologically confirmed supratentorial high-grade glioma will be eligible for this protocol.
Patients must be registered on study within 16 weeks after the surgical procedure that established the diagnosis of High Grade Glioma.
Multicentric glioma
Patients must have malignant glioma or recurrent ependymoma
LOW RISK HIGH-GRADE GLIOMA (patients must meet all of the following criteria):
Patients must have histologically confirmed supratentorial high grade glioma (grade III or IV glioma) that is progressive or recurrent following radiation therapy and chemotherapy; patients with grade IV glioma must have progressed or recurred after initial treatment with radiation and temozolomide; patients with grade III glioma must have received at least radiation and one regimen of chemotherapy (temozolomide or procarbazine, lomustine, vincristine [PCV] regimen)
Chemotherapy for glioma other than temozolomide or Gliadel wafers (steroids are allowed)
Histologically proven intracranial glioblastoma multiforme (WHO grade IV glioma) or gliosarcoma. In addition, the Phase 1b cohort will include patients with progressive WHO grade III glioma.
If most recent histology shows progression to high grade glioma, patients must have had prior radiotherapy in order to be eligible
Patients with pontine glioma are not eligible
COHORT B SPECIFIC INCLUSION: Patients with histologically confirmed glioma of any grade (II-IV) who are planned for a standard of care surgical debulking/resection and for whom participation in this study would not cause a medically unacceptable delay in surgery
PATIENT ONLY: Patients with a diagnosis of HGG or low grade glioma (LGG), based on radiographic or pathologic diagnosis of grade III or IV listed in the medical records, or patients with a malignancy that has metastasized to the brain
BRAIN CANCER: Histologically confirmed high grade glioma
SUBJECT: A child with diffuse intrinsic pontine glioma (DIPG) or recurrent high grade brain tumors will be excluded.
Patients must have histologically confirmed diagnosis of glioma (either low or high grade) and be either chemotherapy naive or non-naive and scheduled to receive temozolomide-based +/- bevacizumab-based chemotherapy; patients with recurrent disease whose diagnostic pathology confirmed glioma (either low or high grade) will not need re-biopsy
Patients must have histologically confirmed high grade glioma by pathology (World Health Organization [WHO] grade III and IV)
Pediatric patients who will receive cranial radiotherapy for brain tumors; this could include but is not limited to: low grade glioma, high grade glioma (to include grade III but not grade IV glioma), germ cell tumors, primitive neuroectodermal tumors, craniopharyngioma, or medulloblastoma
Patients with a suspected diagnosis of new, recurrent, or transformed glioma (WHO grade I-IV) scheduled for craniotomy at Duke University Medical Center (DUMC)
Individuals without a probable or expected grade IV glioma
Histological diagnosis of glioma or
Patients with histologically proven high grade glioma
Histologically-confirmed high-grade glioma
MRI findings compatible with newly diagnosed or recurrent high- or low-grade malignant glioma
Histologically confirmed newly diagnosed grade IV malignant glioma; Note: grade III patients are no longer being enrolled
Suspected or histopathologically proven diagnosis of high or low grade glioma, or a tumor suspected to harbor an isocitrate dehydrogenase (IDH) mutation
Patients must have had prior central nervous system (CNS) radiotherapy for their glioma, including standard doses for low-grade or high-grade glioma as well as non-standard dose and fractionation, including hypofractionated regimens, stereotactic radiosurgery, etc
Subject must have either radiological or established histological diagnosis of the following general categories: \r\n* High-grade glioma/central nervous system (CNS) lymphoma or \r\n* Brain metastases
Suspected new diagnosis or suspected recurrence of glioma
Patients with low-grade (WHO grade I or II) glioma
Any patient with suspected new or recurrent high grade glioma on diagnostic MR imaging who will undergo a resection
Patients must have clinically documented primary brain tumor for which resection is clinically indicated; radiographic findings should be consistent with high grade glioma
Preoperative diagnosis of recurrent high-grade glioma having EGFR positive tissue from prior surgery
Diagnosis of BRAF V600 mutant High Grade glioma that has relapsed, progressed or failed to respond to frontline therapy
Diagnosis of BRAF V600 mutant Low Grade glioma whose tumor is unresectable and who require treatment