Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and well controlled

Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled

Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled

Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and well controlled

Patients with seizure disorder may be enrolled if on non-enzyme inducing anti-convulsants and well controlled

STEP I: Patients must not have active, uncontrolled seizure disorder; patients must have had no seizures in the last 6 months

Patients with a history of uncontrolled seizure disorder; including focal or generalized seizure may not have had a seizure within one year prior to registration

Patients with uncontrolled seizure disorder are not eligible; (patients with seizure disorders that do not require antiepileptic drugs, or are well controlled with stable doses of antiepileptic drugs remain eligible)

Central nervous system function defined as:\r\n* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled\r\n* Patients must not be in status epilepticus, a coma or on assisted ventilation at the time of study enrollment

Patients with a known seizure disorder who are receiving non-enzyme inducing anticonvulsants and have well-controlled seizures may be enrolled

Patients with seizure disorder may be enrolled if on anti-convulsants and well controlled

Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled

Patients with active seizures or a history of uncontrolled seizure disorder, including focal or generalized seizure within the past year

Seizure disorders requiring anticonvulsant therapy.

History of seizure disorder or active use of anticonvulsants

Documented history of or current brain metastases due to seizure risk

Patients with a history of seizure disorder requiring antiepileptic medication or brain metastases with seizures are NOT eligible for participation

History of seizures, prior traumatic brain injury, prior stroke, or other predisposing risk of seizure (excluding CNS metastasis)

Patients with brain metastases (treated or untreated) leptomeningeal disease, uncontrolled seizure disorder, or active neurologic disease

History of uncontrolled seizure disorder

History of seizure or any condition that may predispose to seizure including, but not limited to, underlying brain injury, stroke in the past 6 months, primary brain tumors, brain metastases

Current or history of seizure disorder

Patients with seizure disorder requiring medication

Subject has a history of seizure or any condition that may predispose to seizure including, but not limited to, underlying brain injury, stroke in the past 6 months, primary brain tumors, brain metastases, prior seizures

Patients who have an uncontrolled seizure disorder, or active neurological disease

History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, prior head or traumatic brain injury with loss of consciousness, prior or current space-occupying lesion in the brain); also, history of loss of consciousness or transient ischemic attack within 12 months of day 1 visit

Subjects with a seizure disorder that is not well controlled or who have required a change in seizure medications within 60 days of enrollment to the trial.

History of seizure disorder.

history of seizure disorder

Seizure or known condition that may pre-dispose to seizure (including but not limited to prior stroke or transient ischemic attack within 1 year prior to first dose, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect); loss of consciousness within 12 months may be permitted upon discussion with study principle investigator (PI)

Medications known to lower the seizure threshold must be discontinued or substituted prior to study treatment initiation

History of idiopathic seizure disorder schizophrenia, or psychosis unrelated to glioblastoma, corticosteroid, or anti-epileptic medications.

Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and well controlled

Medications known to lower the seizure threshold (see Appendix 1) must be discontinued or substituted at least 4 weeks prior to study entry.

Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1year to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy)

Patients with a seizure disorder should be well controlled

Patients with seizure disorder may be enrolled if seizure disorder is well controlled

Patients with seizure disorder requiring medication

Patients with seizure disorder requiring medication

Patients with seizure disorder requiring medication

History of seizure or condition that may predispose to seizure; also, history of loss of consciousness or transient ischemic attack within 12 months of (day 1 visit)

Patients must NOT have active clinically significant CNS dysfunction (including but not limited to such as uncontrolled seizure disorder, paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injuries, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination or movement disorder)

Patients with seizure disorder may be enrolled if receiving non-enzyme inducing anticonvulsants and well controlled

History of documented seizure disorder, presence of cerebellar dysfunction, dysphasia or altered mental status on neurological examination

Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and well controlled.

Patients with history of seizure as an adult including febrile seizure or any condition that may predispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization). Also current or prior treatment with anti-epileptic medications for the treatment of seizures. Transient ischemic attack within 12 months prior to study enrollment will not be permitted.

Contraindication to the use of bupropion including seizure disorder or conditions that increase the risk of seizure (including bulimia and/or anorexia nervosa, central nervous system [CNS] tumor, severe stroke, abrupt withdrawal from benzodiazepines or alcohol)

Patients who have a history of a seizure disorder requiring anti-seizure medication.

History of seizure disorder not related to underlying cancer

History of seizure disorder requiring antiepileptic medication or brain metastases with seizures

Serum albumin ? 2 g/dL. Neurologic Function: • Patients with seizure disorder may be enrolled if seizure disorder is well controlled.

History of seizure, seizure disorder, or any condition that may predispose to seizure including, but not limited to underlying brain injury, stroke, primary brain tumors, brain metastases, or alcoholism. Also, history of loss of consciousness or transient ischemic attack within 12 months of enrollment (day 1 visit). Drugs may not be used which are known to decrease the seizure threshold

History or presence of any CNS disorder such as a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement

History of seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement

History of seizure or any condition that may increase the patient’s seizure risk. Also, history of loss of consciousness or transient ischemic attack within 12 months of day 1

Patients with known seizure disorder must have seizures adequately controlled with non- enzyme inducing antiepileptic medications

Subjects must NOT have active clinically significant CNS dysfunction (including but not limited to such as uncontrolled seizure disorder, paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injuries, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination, or movement disorder)

History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, prior head or traumatic brain injury with loss of consciousness, prior or current space-occupying lesion in the brain); also, history of loss of consciousness or transient ischemic attack within 6 months of enrollment

Use of medications known to lower the seizure threshold within 4 weeks prior to study entry

History of seizure disorder

Diagnosis of seizure disorder

Seizures disorder not controlled by anti-seizure medications

Subjects with CNS involvement may be included on the study as long as they have not had any seizure activity in past 4 weeks

Subjects must NOT have active clinically significant CNS dysfunction (including but not limited to such as uncontrolled seizure disorder, paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injuries, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination, or movement disorder)

Any chronic or active neurologic disorder, including seizures and epilepsy, excluding a single febrile seizure as a child

Patients must NOT have active clinically significant central nervous system (CNS) dysfunction (including but not limited to such as uncontrolled seizure disorder, paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injuries, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination or movement disorder

Any history of epilepsy or a seizure disorder or any known prior seizures.

History of neurologic disorder including but not limited to: prior seizure, epilepsy, structural brain abnormality, benign brain tumor, stroke, brain injuries, dementia, movement disorder or other significant CNS abnormalities

Patients will not be eligible if they present or have a history of seizure disorder

FOR ALL PHASES (Ib AND II): Patients with seizure disorder requiring medication

Any chronic or active neurologic disorder, including seizures and epilepsy, excluding a single febrile seizure as a child

Patients with seizure disorder requiring medication

Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and well controlled

Patients with history or presence of clinically significant neurological disorders such as epilepsy, generalized seizure disorder, severe brain injuries are ineligible

Pre-existing (active or severe) neurologic disorders (e.g. pre-existing seizure disorder)

Adequate central nervous system function defined as:\r\n* Subjects with seizure disorder may be enrolled if on anticonvulsants and seizures are well controlled

Seizure disorder requiring medication

Patients with seizure disorder requiring medication

History or presence of non-malignant CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement

Patients with a history of active seizures (or a single confirmed seizure event) in the last 2 years from the time of registration

Prior history of psychiatric disorder or seizure disorders which could be exacerbated by Interleukin-2 as judged by the treating investigator

Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry

Known brain metastases or history of seizure

Uncontrolled seizure disorder (ie, seizures within the past 2 months).

Patients with seizure disorder may be enrolled if receiving non-enzyme inducing anticonvulsants and well controlled

Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year to randomization, brain arteriovenous malformation, schwannoma, meningioma, or other benign central nervous system [CNS] or meningeal disease which may require treatment with surgery or radiation therapy)

Uncontrolled seizure disorder (ie, seizures within the past 2 months).

Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry

History of seizure or condition that may pre-dispose to seizure (including but not limited to prior stroke, transient ischemic attack, loss of consciousness within 1 year prior to randomization, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)

Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry

History of idiopathic seizure disorder, psychosis, or schizophrenia

Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry

History of seizure or known condition that may pre-dispose to seizure (including but not limited to prior stroke or, loss of consciousness within 1 year prior to randomization, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)

History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma) at any time in the past; also, history of loss of consciousness or transient ischemic attack within 12 months of day 1 visit

Known seizure disorder

Clinically evident CNS metastases or leptomeningeal disease not controlled by prior surgery or radiotherapy; history of seizure disorder not controlled by anti-seizure medication at the time of enrollment. Patients with primary CNS malignancies are excluded.

Patients with seizure disorder requiring medication

Seizure disorder requiring enzyme-inducing anti-epileptic drugs (EIAEDs)\r\n* Note: If the seizure disorder can be managed with agents that are not EIAEDs (e.g., levetiracetam or valproate), the patient should not be excluded

REGORAFENIB EXCLUSION CRITERIA: Patients with seizure disorder requiring medication

Patients with seizure disorder requiring medication

Patients with active seizure or history of seizure are not eligible

History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma) at any time in the past; also, history of loss of consciousness or transient ischemic attack within 12 months before day 1

Prior history of seizure disorder

Seizure disorder requiring medication

History of seizure or any condition that may predispose to seizure; history of loss of consciousness or transient ischemic attack within 12 months before day 1

Have a history of a seizure

seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma).

Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and well controlled

Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and well controlled

Documented uncontrolled seizure disorder– a seizure disorder controlled with medication (i.e. no seizures in the previous 6 months) will not exclude a patient

Any chronic or active neurologic disorder, including seizures and epilepsy, excluding a single febrile seizure as a child

Patients with prior history of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain arteriovenous malformation or the use of concomitant medications that may lower the seizure threshold or other conditions predisposing to seizure

Patient does NOT have a history of relevant central nervous system (CNS) pathology or current relevant CNS pathology (non-febrile seizure disorder requiring ongoing anti-epileptic medications, paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injuries, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination or movement disorder)

Patients with a seizure disorder may be enrolled if well-controlled and on non-enzyme inducing anticonvulsants

Reports diagnosis of seizure disorder

Any chronic or active neurologic disorder, including seizures and epilepsy, excluding a single febrile seizure as a child

Clinically evident central nervous system metastases or leptomeningeal disease not controlled by prior surgery or radiotherapy; history of seizure disorder not controlled by anti-seizure medication at the time of enrollment.

Patients with a seizure disorder are study eligible if seizures are controlled on anticonvulsants

Patients with any seizure disorder

History or presence of clinically relevant CNS pathology such as uncontrolled seizure disorder, stroke, severe brain injuries, dementia, cerebellar disease or psychosis

Patients with any history of seizure or seizure disorder

History of seizure disorder

Patients with known active brain metastases, a history of seizure disorder, or other neurological disorders/dysfunction, should be excluded from this clinical trial

History of seizure disorder

Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry

History of seizure or any condition that may predispose to seizures at any time in the past. History of loss of consciousness or transient ischemic attack within 12 months of screening

Patients with seizure disorder may be enrolled if well controlled; patients receiving enzyme-inducing anticonvulsants are not eligible for this study; patients must be off enzyme inducing anticonvulsant drugs (EIACD) for at least 2 weeks prior to registration

Subjects with seizure disorder may be enrolled if on anticonvulsants and well controlled

History of seizure disorder or clinically treated bipolar disorder

Have a seizure disorder where > 1 seizure has occurred within the last year.

History of seizure or any condition that may predispose to seizure; history of loss of consciousness or transient ischemic attack within 12 months before day 1.

Seizure disorders requiring anticonvulsant therapy.

Patients with seizure disorder requiring medication (such as steroid anti-epileptics)

Patients with seizure disorder may be enrolled if seizures are well-controlled (i.e., patients must not have required rescue medications for uncontrolled seizures within 14 days prior to enrollment)

History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma)

History of seizure or condition that may pre-dispose to seizure (e.g., prior stroke within 1 year prior to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system (CNS) or meningeal disease which may require treatment with surgery or radiation therapy

Medications known to lower the seizure threshold

Past or current history of epilepsy or seizure disorder; exception: well-documented febrile seizure of childhood

Patients with seizure disorder requiring medication

Patients with uncontrolled seizures or seizure requiring escalation or addition of anti-epileptic drugs will be excluded

Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled

History of seizure or any condition that may predispose subject to seizure (e.g., prior cortical stroke or significant brain trauma).

History of seizure or any condition that may predispose to seizure within 12 months prior to study treatment, including history of unexplained loss of consciousness or transient ischemic attack

Prior treatment with medications known to lower the seizure threshold within 4 weeks of registration

Seizure or known condition that may pre-dispose to seizure (including but not limited to prior stroke, transient ischemic attack, loss of consciousness within 1 year prior to randomization, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)

Active seizure disorder uncontrolled by medication

Patient has no known history of seizure disorder

Uncontrolled seizure disorder

Patients with a history of seizure disorder (except infant febrile seizures)

Patients with seizure disorder may be enrolled if well controlled

Active seizure or history of seizure disorder

Known central nervous system (CNS) metastases or seizure disorder; patients with known brain metastases that have been successfully treated and stable for >= 6 months without requirement for corticosteroids and without seizure activity will be eligible

Patients with seizure disorder requiring medication

Patients with seizure disorder may be enrolled if on anticonvulsants and if seizures are well controlled

Patients with a high risk of seizures should be excluded from the protocol (e.g. those patients with an uncontrolled seizure disorder, and/or patients who have had a focal or generalized seizure within the last 12 months)

Uncontrolled seizure disorder

Inadequate seizure control

Patients with seizure disorder requiring medication

Seizure or cerebrovascular accident (CVA) in the last year

Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled

Uncontrolled, active seizure disorder or a history of seizure

Treatment with non-enzyme inducing anti-seizure medications is allowed

Concomitant medications that lower seizure threshold

Central nervous system function defined as:\r\n* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled\r\n* Patients must not be in status, coma or assisted ventilation prior to study enrollment

Patients with a history of encephalitis, multiple sclerosis, or seizures within the last year (from seizure disorder or brain metastasis) should be excluded from this clinical trial

Patients with active seizure or a history of seizure are not eligible

History of seizure disorder requiring antiepileptic medication or brain metastases with seizures

Patients must NOT have active seizure(s) or history of seizure(s)

PHASE II: Patients must NOT have active seizure(s) or history of seizure(s)

Patients with a history of seizure disorder requiring antiepileptics who have had a seizure episode within the last 6 months

Central nervous system function defined as\r\n* Patients with a seizure disorder may be enrolled if well-controlled and on non-enzyme inducing anticonvulsants

Patients with history of seizure disorder requiring antiepileptics who have had a seizure episode within the last 6 months

History of uncontrolled severe seizure disorder

History of uncontrolled severe seizure disorder

Patients who have an uncontrolled seizure disorder, or active neurological disease

Patients must not have active, uncontrolled seizure disorder; patients must have had no seizures in the last 6 months

For Cohort C: Has a history of seizure or any condition that may predispose to seizure

Patients who have had a seizure within 12 months prior to enrollment and patients receiving anti-convulsant therapy for a seizure disorder.

Patients must not have active seizure or history of seizure

Subject has a history of seizure or any condition that may predispose to seizure.

History of seizure or any condition that may predispose to seizure;

Patients with seizure disorder requiring medication.

History of seizures or medications known to lower seizure threshold

Uncontrolled seizure disorder, active neurological disease, or known CNS disease.

Comorbid conditions: patients are unable to participate due to the following:\r\n* Generalized or partial seizure disorder that is uncontrolled at the time of registration; the definition of controlled generalized seizures is patients must be on a stable dose of anti-seizure medication and without generalized seizures for at least 10 days prior to registration; the definition of controlled partial seizures is patients must be on a stable dose of anti-seizure medication for at least 10 days prior to registration; patients with occasional breakthrough partial seizures are allowed at treating physician’s discretion\r\n* Grade 3 or 4 thromboembolic disease within 6 months (mo) of registration\r\n* Known history of prolonged QT syndrome

The subject has a history of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma).

A history of seizure within 12 months prior to study entry.

Patients with seizure disorder requiring medication

Patients with seizure disorder requiring medication.

Patients with epilepsy, seizures, or predisposing factors for seizure as judged by the investigator.

Uncontrolled seizure disorder

Patients with a history of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastases, brain arteriovenous malformation or the use of concomitant medications that may lower the seizure threshold

Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and if seizures are well controlled

Patients with seizure disorder requiring medication

Subject has a history of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma, encephalopathy within 3 months of Day 1).

History of seizure including febrile seizure or any condition that may predispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization); also, current or prior treatment with antiepileptic medications for the treatment of seizures or history of loss of consciousness or transient ischemic attack within 12 months prior to randomization

seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma).

History of seizure any time in the past for any reason or any condition that may predispose to seizures.

Patients with seizure disorder requiring medication

Patients with seizure disorder requiring medication

Has a history of seizure

Patients with seizure disorder may be enrolled if seizures are well controlled

History of seizure or any condition or concurrent medication that may predispose to seizure

History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma, history of loss of consciousness or transient ischemic attack within 12 months of study entry); diabetics on a stable dose of insulin or antihyperglycemic regimen are allow if they have had no prior seizures and no history of loss of consciousness due to hypoglycemia

Patients with any seizure disorder requiring medication

Patients with seizure disorder requiring medication

History of seizure or condition that may predispose to seizure (e.g., prior stroke within 1 year of starting study drug, brain arteriovenous malformation)

Concurrent therapy with medications known to have seizure potential

Patients with seizure disorder requiring medication

History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma) at any time in the past; also, history of loss of consciousness or transient ischemic attack within 12 months of day 1 visit

History of seizure or any condition or concurrent medication that may predispose to seizure

Patients with known seizure disorder must have seizures adequately controlled with non-enzyme inducing antiepileptic medications

past history of seizure due to any cause except a single febrile seizure in childhood. Patients with a history of seizures should not have had a seizure within 12 months of Screening and must have had no anticonvulsants for 12 months prior to Screening,

current use of medication that may lower seizure threshold

Subject has a history of seizure within the past 12 months of Screening as assessed by neurology examination and history.

Medications which lowers seizure threshold

History of seizure or any condition that may predispose to seizure including, but not limited to underlying brain injury, stroke, primary brain tumors, brain metastases, or alcoholism; also, history of loss of consciousness or transient ischemic attack within 12 months of enrollment (day 1 visit)

History of epilepsy or seizure disorder

No history of seizure or any condition that may increase the patient’s seizure risk (e.g., prior cortical stroke, significant brain trauma); no history of transient ischemic attack (TIA) within 12 months of enrollment

History of seizure or condition that may pre-dispose to seizure

History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma, history of loss of consciousness or transient ischemic attack within 12 months of study entry) or concurrent medication that may predispose to seizure; diabetics on a stable dose of insulin or antihyperglycemic regimen are allowed if they have had no prior seizures and no history of loss of consciousness due to hypoglycemia

History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma); also, history of loss of consciousness or transient ischemic attack within 12 months of enrollment

History of idiopathic seizure disorder, psychosis or schizophrenia

Any history of seizure or condition that may predispose to seizure

History of seizure, including any febrile seizure, loss of consciousness, or transient ischemic attack, or any condition that may pre-dispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization)

Patients with history of seizure as an adult including febrile seizure or any condition that may predispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization); also, current or prior treatment with anti-epileptic medications for the treatment of seizures or history of loss of consciousness; also transient ischemic attack within 12 months prior to randomization will not be permitted

Any history of seizure or a condition that may pre-dispose to seizure (e.g., prior stroke within 1 year prior to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy).

Concurrent therapy with medications known to have seizure potential (those must have been discontinued or substituted for at least 28 days prior to starting the trial)

No history of seizures or medical conditions which may lower seizure threshold

Any history of seizures or medical condition which lowers seizure threshold

Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled

Patients with known or suspected brain metastases, carcinomatous meningitis, uncontrolled seizure disorder, active intracranial bleeding or active neurologic disorder are excluded

Patients with uncontrolled seizure disorders

No uncontrolled seizure disorders

A history of uncontrolled seizure disorder

Patients must not have a history of any type of seizure for at least 10 years prior to registration.

Patients with seizure disorder requiring medication

Seizure disorder

Concurrent treatment with medications known to have seizure potential

History of seizure or condition that may predispose to seizure

Patients must not have uncontrolled central nervous system disease; patients with a history of seizure disorders must be seizure-free for one year prior to enrollment

Patients with seizure disorder may be enrolled if well controlled

Active central nervous system (CNS) disorder or seizure disorder

Uncontrolled seizure disorder or other serious neurological diseases

Subjects with seizure disorder currently requiring medication.

Known brain metastases, uncontrolled seizure disorders, encephalitis, or multiple sclerosis

Past or current history of epilepsy or seizure disorder

History of seizure or any condition that may predispose to seizure.

History of seizure or any condition that may predispose to seizures (e.g., prior cortical stroke or significant brain trauma) at any time in the past. History of loss of consciousness or transient ischemic attack within 12 months of screening.

Have a seizure disorder requiring medication.

Seizure disorders requiring anticonvulsant therapy

History of seizure disorder

Patients with predisposing factors for seizure including history of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastasis, and brain arteriovenous malformation

Prior history of seizure disorder

History of (a) seizure or any condition that may predispose to seizure (prior cortical stroke or significant brain trauma); (b) loss of consciousness or transient ischemic attack within 12 months prior to day 1 of cycle 1.

History or presence of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement

Uncontrolled seizure disorder or active neurologic disease

Brain metastases, leptomeningeal disease, uncontrolled seizure disorder, or active neurologic disease

Known brain metastases, uncontrolled seizure disorder, or active neurologic disease

Known brain metastases, uncontrolled seizure disorder, or active neurologic disease

History of seizure disorders

Patients with brain metastases (treated or untreated) leptomeningeal disease, uncontrolled seizure disorder, or active neurologic disease

Any history of brain metastases or prior seizure or conditions predisposing to seizure activity

Subjects with seizure disorder may be enrolled if on anticonvulsants and seizures are well controlled

History of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain arteriovenous malformation or the use of concomitant medications that may lower the seizure threshold (not applicable to patients who have already been treated with enzalutamide in first line before inclusion).

Subjects with brain metastases, leptomeningeal disease, uncontrolled seizure disorder, or active neurologic disease

History of seizures (unless seizure free for 5 years);

Uncontrolled seizure disorder or active neurologic disease

Uncontrolled seizure disorder or active neurologic disease

Uncontrolled seizure disorder requiring therapy (such as steroids or anti-epileptics with significant CYP interaction)

Focal or generalized seizure within the last 12 months.

Seizure disorder requiring anticonvulsant therapy (such as steroids or anti-epileptics)

Uncontrolled seizure activity.

Uncontrolled seizure disorder.

History of seizure disorder not related to underlying cancer.

History of seizure or any condition that may predispose to seizure including, but not limited to underlying brain injury, stroke, primary brain tumors, brain metastases, or alcoholism. Also, history of loss of consciousness or transient ischemic attack within 12 months of enrollment (Day 1 visit)

History of seizure or any condition that may predispose subject to seizure (e.g., prior cortical stroke or significant brain trauma). History of loss of consciousness or transient ischemic attack within 12 months of randomization

Evidence of significant central nervous system disease including seizure disorder requiring medication, symptomatic metastatic brain or meningeal tumors

Use of a medication known to lower the seizure threshold within 28 days of first dose of study drug

History of seizure

Patients with active seizures or a history of seizure are not eligible for study entry, with the exception of patients with documented febrile seizure

Donor must have adequate neurologic function as defined by NO evidence of a severe central or peripheral neurologic abnormality and no history of cerebrovascular accident or seizure disorder requiring anticonvulsant medication.

Central Nervous System: Patients without seizure disorder OR patients with well-controlled seizure disorder receiving anticonvulsants may be enrolled on this protocol; anticonvulsants must not be enzyme-inducing (inducers of CYP3A, i.e., no barbiturates, phenytoin, carbamazepine, etc.)

Prior seizures < 3 months prior to enrollment. Subjects with a history of seizure disorders ? 3 months prior to enrollment must be seizure free and on stable anticonvulsant medication(s) for ? 3 months prior to enrollment).

Uncontrolled seizure disorder, active neurological disease, or greater than Grade 2 neuropathy.

Patients with seizure disorder may be enrolled if on anticonvulsants and well-controlled; central nervous system (CNS) toxicity < grade 2

Subjects with uncontrolled seizure

Patients with seizure disorder requiring medication

Seizure disorders

Have a known history of central nervous system disease (e.g., brain metastases or a seizure disorder)

History of intractable epilepsy, or uncontrolled seizure disorder

Patients with bradycardia, seizure disorder or peptic ulcer disease (PUD)

Intractable seizures while on adequate anticonvulsant therapy—more than 1 seizure per week for the past 2 months

History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma) at any time in the past; also, history of loss of consciousness or transient ischemic attack within 12 months of day 1 visit

History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma) at any time in the past; also, history of loss of consciousness or transient ischemic attack within 12 months of the day 1 visit

Medications known to lower the seizure threshold must be discontinued or substituted prior to study treatment

History of seizure or any condition or concurrent medication that may predispose to seizure (including but not limited to prior stroke, transient ischemic attack, loss of consciousness within one year prior to randomization, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)

History of a seizure disorder diagnosis or have experienced a seizure in the past 12 months

History of significant neurological disease including poorly controlled seizures (i.e., > 1 seizure per month; anti-epileptic medications are acceptable), stroke, or head injury with loss of consciousness

PATIENTS: History of neuroleptic malignant syndrome or active seizure disorder (with seizure episode within the past week)

Patient has an active seizure disorder; (patients with a previous history of seizure disorders will be eligible for the study, if they have had no evidence of seizure activity, and they have been free of anti-seizure medication for the previous 5 years)

Survivors who report ever being diagnosed with a seizure disorder or have experienced a seizure in the past 12 months will be excluded

Patients who have a history of head injury or who have known seizure activity

History of seizure disorder

Patients with seizure disorders treated with anticonvulsants

History of seizure or currently taking anti-epileptic medication

Patients who have a history of head injury or who have known seizure activity.

Have a history of seizure or loss of consciousness

Uncontrolled seizure disorder

Patients with seizure disorder requiring medication

Individuals with pre-existing neurological disorder (i.e. brain tumors, dementia, Parkinson’s disease, multiple sclerosis, seizure disorder) or diagnosed with metastasis cancer

Any history of brain metastases or prior seizure or conditions predisposing to seizure activity

History of seizure including febrile seizure or any condition that may predispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization); also, current or prior treatment with antiepileptic medications for the treatment of seizures or history of loss of consciousness or transient ischemic attack within 12 months of enrollment

History of a seizure disorder or requirement for anti-seizure medication

Wearing a pacemaker or implantable cardioverter-defibrillator; uncontrolled seizure disorder

Uncontrolled seizure disorder

Participant has uncontrolled seizure disorder in past 12 months

Patient must not have a seizure disorder

Subjects with a history of seizure disorder taking anti-seizure medication within 30 days prior to randomization.

medical conditions such as seizure disorder, restless leg disorder, or Parkinson's disease

Seizure disorder

Documentation of history of seizure within previous 5 years

Known history of epilepsy/seizure disorder

Reports diagnosis of seizure disorder or a history of neurological illness or closed head injury that in the opinion of the principal investigator (PI) or designated expert(s) feels that it would affect the results of the electroencephalogram (EEG)

Reports diagnosis of seizure disorder or a history of neurological illness or closed head injury that\r\nin the opinion of the principal investigator (PI) feels that it would affect the results of the electroencephalogram (EEG)

Patients with prior seizure history who have experienced a seizure within the three months prior to enrollment are excluded

History of epileptic disorder or any seizure history unrelated to tumor

Patients receiving glucocorticoids and/or anti-seizure medications are eligible for this study

History of seizure, including any febrile seizure, loss of consciousness, or transient ischemic attack, or any condition that may pre-dispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization)

History of neurological disease known to affect cognition prior to initiating chemotherapy (e.g., stroke, head injury with loss of consciousness of > 30 minutes, seizure disorder, demyelinating disorder, mental retardation, primary brain tumor, brain metastases, etc.)

Huntington’s disease, hydrocephalus or seizure disorder

Patients with a seizure disorder are eligible if well-controlled on anticonvulsants; if on a non-enzyme inducing anticonvulsant, the irinotecan (irinotecan hydrochloride) dose will be adjusted as outline in treatment plan

History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma) at any time in the past

History of seizure, including any febrile seizure, loss of consciousness, or transient ischemic attack, or any condition that may predispose to seizure (e.g. prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization)

History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement

Seizure disorder

Patients with a seizure history will not be permitted on protocol; patients on anticonvulsant medications will not be permitted on study