Histologically proven diagnosis of glioblastoma (World Health Organization [WHO] grade IV) confirmed by central review prior to step 2 registration
Participants must have histologically confirmed newly diagnosed glioblastoma or glioblastoma variant (example [ex.] gliosarcoma), including documentation of unmutated isocitrate dehydrogenase (IDH) by immunohistochemistry or sequencing
Patients must have a newly-diagnosed glioblastoma or gliosarcoma that has been confirmed pathologically by a board-certified neuropathologist
Patients must have histologically or cytologically confirmed glioblastoma or other grade IV malignant glioma (i.e. gliosarcoma, small cell glioblastoma, etc.), recurrent after prior external beam fractionated radiotherapy and temozolomide chemotherapy
Participants must have histologically confirmed glioblastoma or variants; subjects with initial diagnosis of a lower grade glioma are eligible if a subsequent biopsy is determined to be glioblastoma or variants
Patients must have histologically confirmed diagnosis of glioblastoma multiforme (GBM) or anaplastic glioma, World Health Organization (WHO) grade 3 or 4
Has known glioblastoma multiforme of the brainstem
recurrent glioblastoma
Glioblastoma.
Patients must have a newly-diagnosed glioblastoma or gliosarcoma that has been confirmed pathologically
Participants must have histologically confirmed glioblastoma and evidence of recurrence > 2 months since last cycle of temozolomide or other alkylating agent; patients with low-grade tumors who have progressed to glioblastoma are eligible
Patients with histologically confirmed glioblastoma or other grade IV malignant glioma (i.e. gliosarcoma, small cell glioblastoma, etc.), recurrent after prior external-beam fractionated radiotherapy and temozolomide chemotherapy
Patients must have histologically proven glioblastoma or gliosarcoma which is progressive or recurrent (per RANO criteria) following radiation therapy and temozolomide
Histopathological evidence of glioblastoma or gliosarcoma, World Health Organization (WHO) grade IV
Patients must have histologically confirmed supratentorial grade IV astrocytoma (glioblastoma multiforme), established by biopsy or resection not more than 3 months prior to registration
Histopathologically proven diagnosis of glioblastoma or gliosarcoma prior to registration by pathology report
Histological confirmation of supratentorial glioblastoma (also known as astrocytoma grade IV, gliosarcoma) amenable to surgical resection =< 28 days prior to registration
Patients must have histologically proven glioblastoma multiforme (GBM) or gliosarcoma (GS)
Have histologically confirmed World Health Organization grade IV malignant glioma (glioblastoma or gliosarcoma); participants will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of glioblastoma or variants is made
Newly diagnosed, histologically-confirmed supratentorial World Health Organization (WHO) grade IV gliomas including glioblastoma (all variants) and gliosarcoma
Previous histologic diagnosis of glioblastoma, transformation to glioblastoma or gliosarcoma established by biopsy or resection prior to enrollment as evident on National Institutes of Health (NIH) or outside pathology
Histopathologically proven newly-diagnosed, supratentorial glioblastoma or gliosarcoma (World Health Organization [WHO] grade IV)
PHASE II DOSE EXPANSION IN RECURRENT GBM UNDERGOING RESECTION: Have histologically confirmed World Health Organization grade IV malignant glioma (glioblastoma or gliosarcoma); participants will also be eligible if the original histology was lower grade glioma and there is suspected transformation to glioblastoma based on imaging findings; if the final pathology report after resection fails to confirm recurrent glioblastoma or gliosarcoma, the subject will be followed for adverse events (AEs) and survival, but excluded for other primary and secondary objective analysis; the subject will be replaced
PHASE II DOSE EXPANSION IN NEWLY DIAGNOSED GBM: Have histologically confirmed World Health Organization grade IV glioma (glioblastoma or gliosarcoma)
PHASE I: Have histologically confirmed World Health Organization WHO grade IV glioma (glioblastoma or gliosarcoma); participants will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of glioblastoma or variants is made
Histologically confirmed diagnosis of World Health Organization grade IV malignant glioma (glioblastoma or gliosarcoma)
Histopathologically confirmed glioblastoma or gliosarcoma (WHO Grade IV) confirmed by local pathology tissue screening.
Radiologic evidence of first recurrence after initial treatment (including surgery, radiation, and temozolomide) or tumor refractory to initial treatment without subsequent treatment in glioblastoma or gliosarcoma (WHO Grade IV). Transformation from a lower grade glioma previously treated with radiation and/or temozolomide to glioblastoma will be considered first recurrence for the purpose of this trial
Histologically confirmed glioblastoma multiforme, World Health Organization (WHO) grade IV astrocytoma
Patients must have histologically or cytologically confirmed glioblastoma multiforme, anaplastic astrocytoma, or gliosarcoma
Patients with recurrent or progressive glioblastoma or other grade IV malignant glioma (e.g. glioblastoma, gliosarcoma, giant cell glioblastoma, etc.) who have failed prior radiation but who have not progressed/recurred on bevacizumab; patients will be eligible if the original histology was lower-grade glioma and subsequent diagnosis of glioblastoma or gliosarcoma is made
Histologic diagnosis of glioblastoma or gliosarcoma (World Health Organization [WHO] grade IV)
First or second relapse of glioblastoma
Histologically proven diagnosis of glioblastoma or gliosarcoma (World Health Organization [WHO] grade IV)
Participants must have histologically confirmed intracranial glioblastoma or gliosarcoma following maximum surgical resection; tumors primarily localized in the infratentorial compartment will be excluded
Participants may have had prior surgery for glioblastoma or gliosarcoma but no systemic or radiation therapy
Participants will not be eligible if the original diagnosis was a lower grade glioma and a subsequent histologic diagnosis revealed glioblastoma
Histologically confirmed glioblastoma or gliosarcoma in 1st, 2nd or 3rd relapse.
Glioblastoma or gliosarcoma disease with leptomeningeal spread.
Newly diagnosed, histologically-confirmed supratentorial World Health Organization (WHO) grade IV gliomas including glioblastoma (all variants) and gliosarcoma.
Have histologically confirmed World Health Organization grade IV glioma (glioblastoma [GB] or gliosarcoma).
Newly diagnosed histologically confirmed unmethylated glioblastoma multiforme (World Health Organization [WHO] grade IV). Patients with secondary glioblastoma, in particular those who are IDH1 or IDH2 mutant, will not be excluded. Unmethylated MGMT must be confirmed by a polymerase chain reaction (PCR)-based assay.
Histologically-confirmed intracranial glioblastoma or gliosarcoma (World Health Organization [WHO] grade IV) with evidence of clinical and radiographic (computed tomography [CT] or MRI brain) tumor progression (need not be biopsy proven)
Part 1 patients must have prior histologically proven glioblastoma that is progressive or recurrent following radiation therapy +/- chemotherapy
Part 2 patients must have histologically confirmed glioblastoma or gliosarcoma
A single glioblastoma or gliosarcoma tumor with histopathological confirmation for first or presenting second recurrence of glioblastoma or gliosarcoma at the time of consent
Pathologically confirmed World Health Organization (WHO) grade IV glioblastoma or variants (gliosarcoma, glioblastoma with oligodendroglial features, giant cell glioblastoma) with adequate tumor material for genomic sequencing; participants will be eligible if the original diagnosis was a lower grade glioma and a subsequent histologic diagnosis of glioblastoma or its variants was made, and they received no prior therapy other than surgery
Patients must have histologically confirmed glioblastoma that is progressive or recurrent following radiation therapy and temozolomide
Histopathologically proven diagnosis of glioblastoma or gliosarcoma (World Health Organization [WHO] grade IV) following either a surgical resection or biopsy
1d. Glioblastoma -Enrollment Completed Have histologically confirmed World Health Organization Grade IV malignant glioma (glioblastoma).
Histologically confirmed glioblastoma. A local pathology report constitutes adequate documentation of histology for study inclusion. Patients with an initial diagnosis of a lower-grade glioma are eligible if a subsequent biopsy was determined to be glioblastoma.
First or second progression of Glioblastoma;
Confirmation by central pathology review of WHO grade IV glioblastoma or gliosarcoma
Newly diagnosed histologically confirmed glioblastoma multiforme (World Health Organization [WHO] grade IV); patients with secondary glioblastoma, in particular those who are IDH1 or IDH2 mutant, will not be excluded
Histopathologically proven diagnosis of glioblastoma or gliosarcoma prior to registration by pathology report
Histologically confirmed newly diagnosed glioblastoma; patients with an initial diagnosis of a lower-grade glioma are eligible if a subsequent biopsy was determined to be glioblastoma and they received no prior treatment
Pathologically confirmed diagnosis of glioblastoma multiforme (GBM); or World Health Organization (WHO) grade IV (gliosarcoma)
Histologically confirmed glioblastoma
Have histologically confirmed World Health Organization grade IV malignant glioma (glioblastoma or gliosarcoma); participants will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of glioblastoma or variants is made
Have histologically confirmed World Health Organization grade IV malignant glioma (glioblastoma or gliosarcoma); participants will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of glioblastoma or variants is made
Glioblastoma or gliosarcoma in first or second recurrence only
Any recurrence of a glioblastoma multiforme
Patients must have tissue confirmation of high grade (World Health Organization [WHO] grade IV) glioma including but not limited to glioblastoma, gliosarcoma, glioblastoma with oligodendroglial features, glioblastoma with primitive neuroectodermal tumor (PNET) features
Histological diagnosis of: glioblastoma or gliosarcoma (World Health Organization [WHO] grade IV) adapted recursive partitioning analysis (RPA) class III, IV, or V
Prior radiation or chemotherapy for glioblastoma or glioma.
Patients must have histologically confirmed diagnosis of glioblastoma multiforme (GBM) or anaplastic glioma, World Health Organization (WHO) grade 3 or 4
Patients with histologically proven supratentorial glioblastoma or gliosarcoma (World Health Organization [WHO] grade IV astrocytoma) will be eligible for this protocol; patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of glioblastoma or gliosarcoma is made prior to any definitive treatment (radiotherapy, chemotherapy)
GBM patients only (enrollment plan 1)\r\n* Histologically confirmed glioblastoma multiforme World Health Organization (WHO) grade III-IV with recurrent or progressive disease after standard therapy\r\n* Age 16 years and older
Part C: Glioblastoma multiforme that has progressed or recurred after radiotherapy and/or chemotherapy
Patients will have histologically proven intracranial glioblastoma multiforme (GBM) or gliosarcoma (GS); this includes treatment-naive patients with prior tissue diagnosis of lower grade gliomas that have been upgraded after repeat resection
Patients with glioblastoma multiforme or gliosarcoma
Patients with histologically proven supratentorial WHO grade IV glioma (glioblastoma or gliosarcoma) will be eligible for the study.
Prior treatment for glioblastoma or gliosarcoma.
Prior treatment with a PI3K and/or mTOR inhibitors for glioblastoma or for pre-existing neoplasm transformed to glioblastoma (applicable for combination treatment arm only)
Histologically confirmed glioblastoma multiforme or gliosarcoma
Glioblastoma or gliosarcoma disease with leptomeningeal spread
Participants with glioblastoma are eligible for this study; these will include\r\n* Those with a histologically proven diagnosis of glioblastoma who have developed new changes on MRI following primary treatment\r\n* Those who received primary treatment for a histologically proven lower grade (2 or 3) glioma and who now progress with radiographic characteristics of transformed glioma
Histologically confirmed GBM or World Health Organization (WHO) Grade IV variants (gliosarcoma, glioblastoma with oligodendroglial features, or giant cell glioblastoma).
Patients will be eligible if the original histology was lower grade glioma and a subsequent diagnosis of glioblastoma or gliosarcoma is made.
Must have histologically proven glioblastoma
Patients must have prior histologically proven glioblastoma that is progressive or recurrent following radiation therapy +/- chemotherapy
Patient with histologically demonstrated, previously untreated glioblastoma
Patients must have histologically confirmed diagnosis of a recurrent/progressive World Health Organization (WHO) grade IV malignant gliomas (glioblastoma multiforme and gliosarcoma)
Histologically proven diagnosis of glioblastoma or other grade IV malignant glioma (including variants of glioblastoma i.e., gliosarcoma, giant cell glioblastoma, etc.).
Diagnoses excluded include: glioblastoma multiforme, gliosarcoma, diffuse pontine glioma, or other tumors presumed to have expected median survival per the investigators of less than 1 year
Patients must have histologically proven glioblastoma or gliosarcoma which is progressive or recurrent following radiation therapy +/- chemotherapy
Histologically confirmed supratentorial glioblastoma or other WHO grade III or IV malignant glioma from archival tissue.
Histologically proven intracranial glioblastoma or gliosarcoma at initial surgery\r\n* Patients will be eligible if the original histology was low-grade glioma and a subsequent diagnosis of glioblastoma or gliosarcoma is made (high-grade transformation)
Participants must have histologically confirmed glioblastoma and evidence of recurrence; patients with low-grade tumors who have progressed to glioblastoma are eligible
Participants must have histologically confirmed glioblastoma and evidence of possible tumor progression on imaging; patients with low-grade tumors who have progressed to glioblastoma are eligible
Primary diagnosis of a glioblastoma
Participants must have histologically or cytologically confirmed newly-diagnosed glioblastoma or gliosarcoma (World Health Organization [WHO] grade IV/IV) and be planning to undergo standard chemoradiation treatment
Participants with multifocal or recurrent glioblastoma
Confirmation of pathology as glioblastoma
newly diagnosed glioblastoma or recurrent/suspected recurrent glioblastoma
Patients with glioblastoma multiforme
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
Only first and second recurrences of GBM are eligible
Subjects must have histologically proven GBM or AA and:
History of more than 2 prior recurrences (including this recurrence) of GBM or AA
Subject has histologically confirmed diagnosis of GBM.
Recovery from the effects of prior GBM surgery as defined by the Investigator;
Have a primary CNS malignancy (eg, GBM).
Have histologically confirmed GBM
Histologically confirmed GBM (WHO grade IV).
Phase I: histologically confirmed grade III or IV malignant glioma\r\nPhase II: histologically confirmed grade IV malignant glioma (GBM)\r\n* Note: GBM variants and secondary GBM, and suspected secondary GBM are allowed for both phase I and phase II
Pathologically confirmed GBM (including all histologic variants) at first diagnosis with radiographic evidence of recurrent disease after treatment with radiotherapy and temozolomide;
Infratentorial disease (defined as glioblastoma [GBM] derived from cerebellum or brainstem)
An interval of >= 4 weeks after the last administration of any other treatment for GBM.
More than two recurrences of GBM.
Had prior treatment of glioblastomas (GBM) with radiation and temozolomide
Biopsy-only of GBM with less than 20% of tumor removed
Prior treatment for GBM (other than surgical resection)
Recurrent or secondary GBM
Prior treatment for GBM (other than surgical resection)
Recurrent or secondary GBM
Must have a clinical diagnosis of Glioblastoma (GBM)
Multifocal, recurrent or metastatic Glioblastoma (GBM) or gliomatosis cerebri (For the sub-study, the subject can have multifocal GBM and gliomatosis cerebri but can't have recurrent or metastatic GBM)
No prior treatment with radiation or chemotherapy for their GBM
Patients must have histologically confirmed initial diagnosis of primary intracranial World Health Organization (WHO) Grade IV malignant glioma (glioblastoma, GBM), now recurrent. Patients with recurrent disease whose initial diagnostic pathology confirmed glioblastoma will not need re-biopsy. Alternately, patients with prior intracranial low-grade glioma or anaplastic glioma will be eligible, if histologic assessment demonstrates transformation to GBM (first diagnosis of secondary GBM).
Patients must have radiographic evidence of recurrent/progressive GBM after prior therapy (biopsy or resection and chemoradiation); 1st recurrence of GBM only, per Response Assessment in Neuro-Oncology Criteria (RANO) criteria. Histologically documented transformation from a lower grade gliomas will be considered first recurrence.
Patients must have been previously treated for GBM with radiation with concurrent and adjuvant temozolomide chemotherapy.
Diagnosis of GBM (World Health Organization [WHO] grade IV); patients who are participating in the optional pre-operative pharmacokinetic study may have presumed GBM based on clinical/radiological findings; however, patient must have histologically confirmed GBM before continuing to receive DSF with concurrent RT/TMZ
Histologically confirmed GBM, WHO grade IV. GBM variants and secondary GBM are allowed in any recurrence (including multiple) and have been treated with radiation and chemotherapy.
PHASE II DOSE EXPANSION IN RECURRENT GBM UNDERGOING RESECTION: Have measurable disease consisting of a minimal volume of 1 cm^3
PHASE II DOSE EXPANSION IN RECURRENT GBM UNDERGOING RESECTION: Has known gliomatous meningitis, subependymal spread, extracranial disease, or multifocal disease
PHASE II DOSE EXPANSION IN RECURRENT GBM UNDERGOING RESECTION AND IN NEWLY DIAGNOSED GBM: Has received prior therapy with any antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
Histologically confirmed primary glioblastoma multiforme (GBM)
Patient must be diagnosed with recurrent GBM either with biopsy or radiographically
Patients will have histologically proven intracranial glioblastoma multiforme (GBM) or gliosarcoma (GS); this includes treatment-naive patients with prior tissue diagnoses of lower grade gliomas that have been upgraded to GBM after repeat resection
Prior chemotherapy for recurrent GBM with nitrosourea compounds including Gliadel® wafers or bevacizumab.
Patients must have histologically proven GBM that is progressive or recurrent following standard RT and temozolomide (i.e., at least “biopsy-proven” recurrent disease); previous salvage therapies after first recurrence do not exclude subjects from this trial (e.g., anti-angiogenesis therapies, second- and third-line chemotherapies); patients will be eligible if the original histology was lower-grade glioma and a subsequent diagnosis of GBM is made; for subjects who have tumor resection within the translation sub-study, the pathology results will be reviewed post-surgery and prior to treatment on the main study
A history of biopsy-confirmed exclusive radionecrosis after initial GBM therapy
Patients with histologically confirmed GBM and/or other glioma subtypes at the time of diagnosis or prior relapse.
Histologically proven intracranial Glioblastoma Multiforme (GBM) with diagnosis established by biopsy or resection within 5 weeks prior to enrollment.
Newly diagnosed glioblastoma (GBM) histologically proven, World Health Organization (WHO) grade IV GBM or WHO grade IV gliosarcoma.
PART 1 PATIENTS (SURGICALLY ELIGIBLE RECURRENT GBM)
Patients must have histologically-proven GBM
Histologically proven GBM
Prior taxane, vincristine, or other microtubule inhibitor chemotherapies for treatment of GBM or other malignancy
No more than 5 prior anticancer regimens for advanced (recurrent, locally advanced or metastatic) disease except for patients with GBM which must have first recurrence of GBM by diagnostic biopsy or contrast enhanced magnetic resonance imaging (MRI).
Prior histologic diagnosis of GBM or gliosarcoma at first occurrence
First or second recurrence of GBM or gliosarcoma considered to be surgically resectable
Confirmed histological diagnosis of recurrent GBM or gliosarcoma
Histologically confirmed GBM at first or second recurrence after concurrent or adjuvant chemotherapy or radiotherapy (must have received temozolomide).
Biopsy proven supratentorial GBM that has not undergone previous surgical resection, radiation and/or chemotherapy
Patients with multiple or multifocal GBM
Histologic documentation: newly diagnosed World Health Organization (WHO) grade IV intracranial glioblastoma or gliosarcoma; GBM with oligodendroglial features are NOT PERMITTED in this study if they are 1p19q codeleted; sites submitting GBM with oligodendroglial features will be asked to provide results of 1p/19q codeletion status
Subjects with Glioblastoma multiforme (GBM) do not have to have objectively measurable disease at entry.
For glioblastoma multiforme (GBM-2) cohort:
Primary GBM or gliosarcoma
Histologically documented diagnosis of proven glioblastoma (GBM)
Histologically confirmed initial diagnosis of primary glioblastoma multiforme (GBM) or gliosarcoma (GS), now recurrent. Patients with recurrent/progressive disease whose initial diagnostic pathology confirmed GBM or GS will not need re-biopsy. Patients with prior low-grade glioma or anaplastic glioma are eligible, if histologic assessment demonstrates transformation to GBM or GS.
No prior treatment with radiation or chemotherapy for their GBM
Any prior treatment for the patient's GBM including radiation or chemotherapy
Major Eligilbility Criteria\n\n          1. Signed written informed consent must be obtained and documented according to\n             International Conference on Harmonisation (ICH) and local regulatory requirements.\n\n          2. A histologically confirmed supratentorial glioblastoma (GBM) at first\n             recurrence/progression (except for transformation from previous low grade glioma)\n             following standard front-line therapy, for which treatment with temozolomide (TMZ)\n             would be acceptable as determined by the Investigator\n\n          3. Previously received standard front-line GBM treatment including maximal surgical\n             resection followed by external beam radiation therapy.\n\n          4. Patients may or may not be candidates for repeat surgical resection of the\n             recurrent/progressed GBM.\n\n          5. Patients must have unequivocal evidence of tumor recurrence/progression by MRI at a\n             minimum of 12 weeks following completion of chemoradiation or radiation therapy.\n\n          6. Patients must have measurable or non-measurable disease by response assessment in\n             neuro-oncology (RANO) criteria\n\n          7. ?18 years of age.\n\n          8. Eastern Oncology Cooperative Group (ECOG) performance status of 0 or 1
First recurrence of GBM (Cohorts 1, 1b and 2 only)
First diagnosis of GBM with resectable disease (Cohorts 1c Part A only)
More than 1 recurrence of GBM (Cohorts 1, 1b and 2 only)
Any recurrence of GBM (Cohorts 1c and 1d only)
Patients with histologically proven intracranial glioblastoma multiforme (GBM) or gliosarcoma (GS); patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a GBM or GS is made; patients must have evidence of progression of the GBM or GS on magnetic resonance imaging (MRI) or computed tomography (CT) scan
Histologically confirmed glioblastoma multiforme (GBM); rare GBM variants, secondary GBM, and suspected GBM are allowed
Evidence of recurrent GBM or metastases detected outside of the cranial vault.
For Arm B, patients must be at first recurrence of GBM and must not have had prior anti-VEGF therapy
For Arm C, patients may have had an unlimited number of prior therapies for GBM, however must be at first recurrence from a therapeutic regimen containing bevacizumab
Histologically proven supratentorial GBM or gliosarcoma
Histologically proven GBM
Prior taxane, vincristine, or other microtubule inhibitor chemotherapies for treatment of GBM or other malignancy
Histological diagnosis of GBM (WHO grade IV)
Histology other than astrocytoma grade IV (GBM or gliosarcoma)
Histologically confirmed GBM
Histologically or cytologically confirmed unresectable GBM. Subjects with recurrent disease whose prior pathology demonstrated GBM will not need to be re-biopsied. Subjects with prior low-grade glioma or anaplastic glioma are eligible if histological assessment demonstrates transformation into GBM.
Histologically confirmed glioblastoma multiforme (GBM) (World Health Organization [WHO] grade IV); rare GBM variants (e.g. gliosarcoma, giant cell GBM, small cell GBM, GBM with oligodendroglioma features, GBM with primitive neuroectodermal tumor [PNET] features) are allowed; patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of GBM is made
Unequivocal evidence of recurrent or progressive GBM before or after bevacizumab treatment first based on radiographic appearances then confirmed by histologic confirmation through biopsy or resection
Patients must agree to forgo any other treatments, including but not limited to cytotoxic or biologic chemotherapies, that are intended to treat the recurrent GBM while receiving treatment with NovoTTF therapy
Patient has histologically confirmed diagnosis of GBM with documented recurrence after first line treatment including radiotherapy and TMZ (SoC), not suitable for curative surgery or re-irradiation.
Patient has received previous antineoplastic treatment for recurrent GBM (e.g. VEGF inhibitors, cytotoxic agents).
Glioblastoma Multiforme (GBM)
Recurrent GBM per RANO criteria
For Subjects with recurrent GBM in Arm B, subject has received prior treatment with bevacizumab, nitrosourea, or has secondary GBM
For Subjects with recurrent GBM in Arm C, subject has received prior treatment with bevacizumab, or has secondary GBM
Participants with GBM can be enrolled 2 weeks after last treatment
Up to 6 patients with recurrent/relapsed glioblastoma multiforme (GBM/AnaA) or with grade 3 anaplastic astrocytomas that with a history of progression or recurrence following radiotherapy and an alkylating agent (e.g. temozolomide) Patients with other disease types may be enrolled into the expansion phase upon approval of the Sponsor.
If GBM, previously treated for GBM with surgery and/or radiation, if appropriate, and must have failed both bevacizumab (Avastin) and temozolomide (Temodar), unless either or both are contraindicated.
Patient may have received initial treatment for GBM as follows:
For patients enrolled into Stage II, they must be within ? 2 weeks but ? 6 weeks after primary GBM resection/biopsy The patient must have recovered from the definitive surgical procedure for GBM
Patient has received previous treatment with PI3K and/or mTOR inhibitors for GBM or for pre-existing neoplasm transformed to GBM. Patient has received any prior anti-neoplastic therapy for BKM, except for the treatment allowed in inclusion criteria
RANDOMIZED INTERVENTION: Current ICs to a patient with GBM
Histologically proven diagnosis of GBM.
No history of uncontrolled seizures after surgery for primary GBM (despite adequate antiepileptic therapy) or with need for concurrent administration of more than 2 antiepileptic drugs.
Participants must have evidence of metastatic cancer to the brain for cohort A or histologically confirmed glioblastoma (GBM) for cohorts B and C
Those with GBM but suspected to have pseudoprogression at any time after completion of chemoradiation can enroll in cohort C
Subjects must have a known or presumed radiological diagnosis of glioblastoma (GBM); for presumed diagnosis of GBM, histological confirmation of GBM must be completed within 12 weeks of enrollment; (subjects will be removed from study and non-evaluable if no histologic diagnosis of GBM is confirmed)
Karnofsky performance status (KPS) >= 60 (Parts 2 [intracranial tumor patients] and 3 [recurrent glioblastoma (GBM) patients] ONLY)
(Part 3, suspected recurrent GBM patients ONLY): Any patient with histopathologically proven GBM who, on a standard of care surveillance brain magnetic resonance imaging (MRI), has an imaging change suspicious for GBM recurrence, and whose treatment plan for the recurrence does not include surgery
(Part 3, suspected recurrent GBM patients ONLY): Life expectancy of >= 6 months
(Part 3, suspected recurrent GBM patients ONLY): Has already begun non surgical therapy for any recurrence, prior to the first [18F]DASA 23 PET/MRI scan
If an initial biopsy demonstrates neoplasm other than GBM