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