Patients are eligible if central nervous system (CNS) metastases are adequately treated and neurological symptoms have returned to baseline or are controlled for at least 2 weeks prior to enrollment; in addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of =< 10 mg daily prednisone (or equivalent); patients with untreated CNS metastases are eligible if they are not symptomatic and the lesions are less than 1 cm in size
Patients with central nervous system (CNS) metastases with the following exceptions: Patient untreated CNS metastases with 5 or fewer sites of disease, with no single site larger than 20 mm, are eligible if they are asymptomatic and not requiring steroids at any dose; patients with asymptomatic CNS metastases may be treated with radiosurgery before or during therapy on trial without treatment delays; patients with treated, symptomatic CNS metastases are eligible if they are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to registration AND either off corticosteroids, or on a stable or decreasing dose of =< 10 mg daily prednisone (or equivalent)
Clinically asymptomatic and stable central nervous system (CNS) metastases are allowed (including untreated CNS metastases) if they have not required increasing doses of steroids or stable doses equivalent to prednisone > 10 mg daily within 2 weeks prior to study entry for CNS symptoms
Known untreated brain or leptomeningeal metastasis\r\n* Patients with brain metastases are eligible if metastases have been adequately treated and neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least two weeks prior to C1D1 and meet requirements related to steroids
Participants with untreated CNS metastases are excluded. Participants are eligible if CNS metastases are adequately treated and participants are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to first treatment
Subjects with symptomatic CNS metastases who are neurologically unstable and/or require an increased dose of steroid to manage CNS symptoms within 1 week prior to the first day of treatment are excluded\r\n* Subjects with brain or leptomeningeal metastases that do not meet the above criteria are allowed\r\n* Symptomatic disease is allowed as long as symptoms are controlled and stable
Patients having active central nervous system (CNS) metastases; patients adequately treated and neurologically returned to baseline (except for residual signs of symptoms related to the CNS treated) for at least 2 weeks prior to enrolment are allowed; in addition, patients must be either off corticosteroids or on a stable or decreasing dose of < 10 mg daily prednisone or equivalent
Patients with known CNS metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth.
Participants with known untreated brain metastases should be excluded from this clinical trial; subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to study entry; subjects must be either off corticosteroids, or on a stable or decreasing dose of ? 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to first study treatment
Subjects with active (i.e. symptomatic or growing) central nervous system (CNS) metastases. Subjects with CNS metastases are eligible if the metastases have been treated with surgery and/or radiotherapy, the subject is off corticosteroids for at least 2 weeks and the subject is neurologically stable.
Presence of symptomatic central nervous system (CNS) metastases or CNS metastases that require local CNS-directed therapy (e.g. radiotherapy or surgery) or increasing doses of corticosteroids within the prior 2 weeks. Patients with treated brain metastases should be neurologically stable (for 4 weeks post-treatment and prior to study enrollment) and off of steroids for at least 2 weeks before administration of any study treatment.
Subjects with active central nervous system (CNS) metastases are excluded; if CNS metastases are treated and subjects are at neurologic baseline for at least 2 weeks prior to enrollment, they will be eligible but will need a brain magnetic resonance imaging (MRI) prior to enrollment; subjects must be off corticosteroids or on a stable or decreasing dose of =< 10 mg daily prednisone (or equivalent)
Subjects with active central nervous system (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention, including leptomeningeal disease, are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy.
Subjects with active central nervous system (CNS) metastases with significant neurological compromise or symptoms are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy), who show no evolving new neurological symptoms are eligible for the study.
Subjects with active central nervous system (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention are excluded; subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy; subjects with CNS metastases incidentally detected during screening which do not cause clinical symptoms and for which standard of care suggests no therapeutic intervention is needed are eligible
Subjects with active central nervous system (CNS) metastases are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy.
Subjects with symptomatic untreated CNS metastases are excluded\r\n* Subjects are eligible if CNS metastases are asymptomatic or adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to first treatment\r\n* In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ? 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to first treatment
Subjects with active central nervous system (CNS) metastases are excluded; if CNS metastases are treated and\r\nsubjects are at neurologic baseline for at least 2 weeks prior to enrollment, they will be eligible but will need a brain magnetic resonance imaging (MRI) prior to enrollment; subjects must be off corticosteroids or on a dose of less than 10 mg per day
Any history of CNS metastases that is not adequately treated (surgery or radiation) > 14 days prior to registration
Subjects with active central nervous system (CNS) metastases are excluded. Subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 4 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of =< 10 mg daily prednisone (or equivalent) for 2 weeks.
Subjects with CNS metastases are only eligible if the CNS metastases are treated with radiotherapy and/or surgery and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment); in addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of =< 10 mg daily prednisone (or equivalent)
Active CNS metastases; however, patients with CNS metastases will be eligible if they have been treated and are stable without symptoms for 4 weeks after completion of treatment, with image documentation required, and must be off steroids.
Subjects with active central nervous system (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention are excluded; subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy; subjects with CNS metastases incidentally detected during screening which do not cause clinical symptoms and for which standard of care suggests no therapeutic intervention is needed are eligible
Subjects with untreated symptomatic central nervous system (CNS) metastases are excluded\r\n* Subjects are eligible if symptomatic CNS metastases are treated and subjects have neurologically returned to baseline (except for residual signs and symptoms related to CNS treatment) for at least 7 days prior to first dose of study treatment\r\n** Subjects must be off corticosteroids for at least 7 days prior to first dose of study treatment
Known active CNS metastases and/or carcinomatous meningitis a. To be eligible for the study treatment, subjects must have stable disease ? 1 month, confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and have CNS metastases well controlled by low-dose steroids, anti-epileptics, or other symptom-relieving medications.
Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth; patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated (eg, radiotherapy, stereotactic surgery) and are clinically stable off anticonvulsants and steroids for at least 4 weeks before randomization
Known active CNS metastases and/or carcinomatous meningitis • To be eligible for the study treatment, subjects must have stable disease ? 3 months, confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and have CNS metastases well controlled by low-dose steroids, anti-epileptics, or other symptom-relieving medications
Known untreated brain or leptomeningeal metastasis\r\n* Patients with brain metastases are eligible if metastases have been adequately treated and neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least two weeks prior to C1D1
Active CNS metastases or carcinomatous meningitis. Patients with CNS lesions that have been treated and who have no evidence of progression in the brain on CT/MRI for ?1 month are eligible. Pregnant or nursing women due to the unknown effects of immunization on the developing fetus or newborn infant.
Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. However, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 4 weeks prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis on brain imaging within 4 weeks of enrollment (2) off steroids for 2 weeks. Patients with clinically insignificant brain metastases that do not require treatment are eligible
Patients with known active CNS metastases and/or carcinomatous meningitis; however, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 1 month prior to entry as defined as:\r\n* No evidence of new or enlarging CNS metastasis\r\n* Off steroids that are used to minimize surrounding brain edema; patients with clinically insignificant brain metastases that do not require treatment are eligible
Known CNS metastases or carcinomatous meningitis. Subjects with previously treated, stable CNS metastases (no evidence of progression for ? 4 weeks, and resolution of neurologic symptoms to baseline state) are permitted in this study.
Patients with treated, symptomatic CNS metastases are eligible if they are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to registration AND either off corticosteroids, or on a stable or decreasing dose of ? 10 mg daily prednisone (or equivalent).
Any active central nervous system (CNS) lesion (i.e., those with radiographically unstable, symptomatic lesions) and/or leptomeningeal metastases; NOTE: patients treated with stereotactic radiotherapy or surgery are eligible if no evidence of CNS disease progression >= 4 weeks and patients must be off corticosteroid therapy for >= 3 weeks; NOTE: carcinomatous meningitis is excluded regardless of clinical stability
Known active central nervous system (CNS) metastases or carcinomatous meningitis; patients with CNS metastases including brain metastases who have completed a course of radiotherapy are eligible for the study provided they are clinically stable; however, oral corticosteroids for control of CNS symptoms are not allowed on study
Has active central nervous system (CNS) metastases (including evidence of cerebral edema by MRI, or progression from prior imaging study, or any requirement for steroids, or clinical symptoms of/from CNS metastases) within 28 days prior to study treatment. Subjects with known CNS metastases must have a baseline MRI scan within 28 days of study treatment.
Subject has primary central nervous system (CNS) tumor or known CNS metastases and/or history of CNS metastases and/or carcinomatous meningitis; Exception: Subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 4 weeks prior to enrollment. In addition, subjects must be off corticosteroids for 4 weeks prior to enrollment.
Subjects with active central nervous system (CNS) metastases are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy
Known brain metastases, unless previously treated and patients are neurologically returned to baseline except for residual signs and symptoms related to Central Nervous System (CNS) treatment and CNS lesions are not progressive in size and number for 4 weeks.
Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated with local therapy (eg, radiotherapy, stereotactic surgery) and are clinically stable off anticonvulsants and steroids for at least 4 weeks before randomization.
Have untreated central nervous system (CNS) metastases. Patients are eligible for study participation if CNS metastases are adequately treated and patients are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 60 days prior to consent. In addition, patients must either be off corticosteroids, or on a stable or decreasing dose of 10 mg daily prednisone (or equivalent) for at least 60 days prior to consent.
Subjects with active central nervous system (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention are excluded
Subjects with active central nervous system (CNS) metastases are excluded; subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrollment; in addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of =< 10 mg daily prednisone (or equivalent) for 2 weeks
Patients with active CNS metastases or carcinomatous meningitis, except patients with CNS lesions that have been treated and have no evidence of progression in the brain on CT/MRI for ? 3 months.
Active CNS metastases or carcinomatous meningitis. Patients with CNS lesions that have been treated and who have no evidence of progression in the brain on CT/MRI for ?1 month are eligible.
No signs or symptoms of CNS metastases (mets) within the last 30 days (from enrollment evaluation)
Active central nervous system (CNS) disease, metastases or carcinomatous meningitis. Patients with CNS metastases must be at least 2 weeks status post prior therapy to the brain and be off all steroids without progressing CNS disease.
Subjects with untreated central nervous system (CNS) metastases are excluded. Subjects are eligible if CNS metastases are asymptomatic or treated and subjects are neurologically returned to baseline for at least 2 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ?10mg daily prednisone (or equivalent)
Patient has known active CNS metastases and/or carcinomatous meningitis; however, patients with CNS metastases (including brain metastases) who have completed a course of radiotherapy are eligible for the study provided they are clinically stable; oral corticosteroids for control of CNS symptoms are allowed
Subjects with central nervous system (CNS) metastases, unless they have been treated and are stable without symptoms for 4 weeks after completion of treatment and must be off steroids for at least 4 weeks prior to enrollment
Known active central nervous system (CNS) metastases. Subjects with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 1 month prior to study entry, defined as:
Patients with symptomatic CNS metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.
Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; however, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 1 month prior to entry as defined as: \r\n* No evidence of new or enlarging CNS metastasis \r\n* Off steroids that are used to minimize surrounding brain edema
Known central nervous system metastases causing clinical symptoms or metastases that require therapeutic intervention. Subjects with a history of treated central nervous system (CNS) metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy. Subjects with CNS metastases incidentally detected during Screening that do not cause clinical symptoms and for which standard of care suggests no therapeutic intervention is indicated, should be discussed with the Sponsor Medical Responsible
Active (i.e., symptomatic or growing) central nervous system (CNS) metastases. Subjects with CNS metastases are eligible for the trial if: a. the metastases have been treated by surgery and/or radiotherapy, b. the subject is off corticosteroids (>10 mg/day) and is neurologically stable for at least 2 weeks prior to Screening. c. brain MRI completed within 3 months of Screening.
Patients with known symptomatic, untreated central nervous system (including brain, spinal cord)\r\n* Patients who have a history of brain/central nervous system (CNS) metastasis are eligible for the study provided that all the following criteria are met:\r\n** Brain/CNS metastases which have been treated\r\n** No evidence of disease progression for >= 3 months before the first dose of study drug \r\n** No hemorrhage after treatment\r\n** Off-treatment with dexamethasone for 4 weeks before administration of the first dose of TAK-228\r\n** No ongoing requirement for dexamethasone or anti-epileptic drugs
Patients with brain metastases or primary brain tumors must have completed treatment, surgery or radiation therapy >= 28 days prior to registration and have stable disease at time of registration; metastatic brain parenchymal disease must have been treated and patient must be off steroids for 7 days prior to registration; patients must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to registration
Patients must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to sub-study registration; patient must not have leptomeningeal disease, spinal cord compression or brain metastases unless: (1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 14 days following treatment and prior to registration, AND (2) patient has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to sub-study registration
Patients are ineligible if they have any currently active central nervous system (CNS) metastases; patients who have treated brain metastases (with either surgical resection or stereotactic radiosurgery [SRS]) could be eligible; patients must not have taken any steroids =< 10 days prior to randomization for the purpose of managing their brain metastases; patients with only whole brain irradiation for treatment of CNS metastases will be ineligible
Patients are ineligible if they have any currently active CNS metastases; patients who have treated brain metastases (with either surgical resection or stereotactic radiosurgery [SRS]) could be eligible to proceed; patients crossing over from dabrafenib/trametinib to nivolumab (nivo)/ipilimumab (ipi) must not have taken any steroids =< 10 days prior to registration for the purpose of managing their brain metastases; patients with only whole brain irradiation for treatment of CNS metastases are ineligible
Patients with central nervous system (CNS) metastases must have all lesions adequately treated with stereotactic radiation therapy, craniotomy, gamma knife therapy, or whole brain radiotherapy, with no subsequent evidence of CNS progression; patients must not have required steroids for at least 14 days prior to registration
Patients must have had no prior radiation therapy with the exception of CNS irradiation of brain metastases; (this exception only applies to SR1 patients; any patients over age 11 with distant metastases to brain [stage IV disease] would be considered poor risk and therefore not eligible for this trial)
Patients with known central nervous system (CNS) metastases are not eligible; Note: brain imaging is not an eligibility requirement
Patients with known or suspected central nervous system (CNS) metastases, untreated CNS metastases, or with the CNS as the only site of disease are excluded; however, subjects with controlled brain metastases will be allowed to enroll; controlled brain metastases are defined as no radiographic progression for at least 4 weeks following radiation and/or surgical treatment (or 4 weeks of observation if no intervention is clinically indicated), and off of steroids for at least 2 weeks, and no new or progressive neurological signs and symptoms
Active, untreated central nervous system (CNS) metastasis (subjects with brain metastases who are identified at screening may be rescreened after the lesion[s] have been appropriately treated and subjects are off corticosteroids)
Participants with known brain metastases may be enrolled in this study if radiation therapy and/or surgery have been completed with a minimum of 4 weeks of stable disease demonstrated on evaluation by magnetic resonance imaging (MRI); such participants must no longer require treatment with corticosteroids or enzyme inducing anti-epileptic medications for their central nervous system (CNS) disease
Prior central nervous system (CNS) disease is allowed if stable for at least one month since whole brain radiation therapy, and 2 weeks since stereotactic radiotherapy, and not requiring steroids; patients whose CNS disease was surgically treated may be enrolled if stable for at least one month, and not requiring steroids
Active, non-stable brain metastases or CNS disease
Subjects with ? 3 brain metastases and each ? 1 cm size that were treated with either surgical resection and/or radiation therapy are eligible for study participation provided (a) there is no evidence of progressive central nervous system (CNS) disease on brain imaging at least 30 days after definitive treatment and (b) the subject is not taking prednisone at >10 mg or equivalent daily.
Subjects with > 1 cm or > 3 in number treated brain metastases are eligible for study participation provided (a) there is no evidence of progressive CNS disease on brain imaging at least 90 days after treatment with surgery and/or radiation therapy and (b) if the subject is not taking prednisone at >10 mg or equivalent daily.
Patients with central nervous system (CNS) metastases must be stable after therapy for CNS metastases (such as surgery, radiotherapy or stereotactic radiosurgery) for at least 4 weeks and must be off steroid treatment for 2 weeks prior to study enrollment
Patients with central nervous system metastases are excluded; Note: subjects with previously treated (radiotherapy or surgery) brain metastasis that have been stable without steroid treatment for at least 3 months following prior treatment may be enrolled
History of central nervous system (CNS) disease; Note: patients with brain metastases will be eligible if treated appropriately and if they remain clinically stable neurologically; for asymptomatic brain metastases, appropriate clinical treatment may include observation with serial imaging
Patients with previously untreated brain metastases (including parenchymal, meningeal or dural-based central nervous system [CNS] lesions) are excluded; however, patients with previously treated (surgery, radiation or both), clinically inactive brain metastases, who have not received corticosteroid therapy within three weeks of starting protocol therapy, are eligible
Patients with symptomatic brain metastases are excluded. Patients with asymptomatic and treated CNS metastases may participate in this trial. The patient must have completed any prior treatment for CNS metastases > 28 days prior to study entry including radiotherapy or surgery. Steroids for the treatment of brain metastasis are not permitted, and patients must be stable off steroid treatment for 4 weeks prior to enrollment.
No uncontrolled central nervous system (CNS) disease, including parenchymal brain metastases, leptomeningeal disease, or spinal cord compression; patients with asymptomatic untreated brain metastases are eligible; patients with treated CNS disease will be allowed to enroll provided they have clinically confirmed stable disease with >= 2 weeks since definitive CNS therapy (radiation or surgery) and >= 2 weeks without systemic steroids; patients may undergo either whole brain radiation or stereotactic radiosurgery prior to study entry
Participants with symptomatic central nervous system (CNS) metastases who are neurologically unstable and/or require radiation therapy are excluded;\r\n* Participants with brain metastases that do not meet the above criteria in the opinion of the treating investigator \r\n* Symptomatic disease is allowed as long as symptoms are controlled and stable
Participants with Central Nervous System (CNS) metastases are not eligible, unless they have completed local therapy for at least 4 weeks and have discontinued the use of corticosteroids for this indication or are on a tapering regimen of corticosteroids (defined as ?10 milligrams [mg] prednisolone equivalent) before starting treatment in this study. Any signs (eg, radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment.
For part 1 (dose escalation) only, patients with previously diagnosed brain metastases are eligible as long as they do not require central nervous system (CNS)-directed therapy (including corticosteroids); if the patient has had radiation therapy or surgery, then they should have completed treatment and have discontinued corticosteroids for at least 2 weeks and must be neurologically stable; patients with brain metastases are excluded from part 2 (dose expansion)
No uncontrolled central nervous system (CNS) disease, including parenchymal brain metastases, leptomeningeal disease, or spinal cord compression; patients with asymptomatic untreated brain metastases are eligible; patients with treated CNS disease will be allowed to enroll provided they have clinically confirmed stable disease with >= 2 weeks since definitive CNS therapy (radiation or surgery) and >= 2 weeks without systemic steroids; patients may undergo either whole brain radiation or stereotactic radiosurgery prior to study entry
Participants with asymptomatic CNS metastases with previous or concomitant brain deficiencies, as defined in the protocol
Patients with known leptomeningeal or brain metastases should be excluded from this clinical trial; imaging or spinal fluid analysis to exclude central nervous system (CNS) involvement is not required, unless there is clinical suspicion by the treating investigator
Known untreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsant medications or corticosteroids for symptomatic control); a CT or MRI scan of the brain will be performed at screening if required by the local health authority
The patient has known active or suspected brain or leptomeningeal metastases. (Central nervous system [CNS] imaging is not required prior to study entry unless there is a clinical suspicion of CNS involvement). Patients with stable, treated brain metastases are eligible provided there is no evidence of CNS disease growth on imaging for at least 3 months following radiation therapy or other locoregional ablative therapy to the CNS.
Subject has known active central nervous system (CNS) involvement; the subject has untreated brain or meningeal metastases; CT scans are not required to rule out brain or meningeal metastases unless there is a clinical suspicion of central nervous system disease; subjects with treated brain metastases that are radiographically or clinically stable for at least 4 weeks after therapy and have no evidence of cavitation or hemorrhage in the brain lesion(s) are eligible, providing that they are asymptomatic, and do not require corticosteroids (must have discontinued steroids at least 1 week prior to study drug administration)
CNS metastases, unless treated w/ surgery, whole brain radiation or stereotactic radiosurgery, and stable disease ?8 wks w/o steroid use for ?4 wks prior to study drug
Patients with known brain metastases should be excluded from this clinical trial; patients with brain metastases diagnosed greater than 1 year prior to study entry may be considered if they received sterilizing therapy to the central nervous system (CNS) (resection or radiation) and have been CNS recurrence-free for the 1-year period
Patients with known leptomeningeal or brain metastases; imaging or spinal fluid analysis to exclude central nervous system (CNS) involvement is not required, unless there is clinical suspicion by the treating investigator
Patients with active central nervous system (CNS) metastases or leptomeningeal involvement by tumor (patients with a history of brain metastases who have successfully treated for brain metastasis by surgery or radiation and who have not had any evidence of the new or progressive CNS disease for more than 12 months are eligible)
Known active brain or central nervous system metastasis (less than 2 months out from definitive radiotherapy or surgery), seizures requiring anticonvulsant treatment (< 3 months) or clinically significant cerebrovascular accident (< 3 months); in order to be eligible patients must have repeat central nervous system (CNS) imaging at least two months after definitive treatment showing stable CNS disease; patients with evidence of intratumoral or peritumoral hemorrhage on baseline imaging are also excluded unless the hemorrhage is grade =< 1 and has been shown to be stable on two consecutive imaging scans
Patients with active central nervous system (CNS) lesions are excluded (i.e., those with radiographically unstable, symptomatic lesions); however, patients treated with stereotactic therapy or surgery are eligible if they remain without evidence of disease progression in the brain for >= 3 weeks
Uncontrolled central nervous system (CNS) metastases, including leptomeningeal metastases, are not allowed; subjects with previously treated brain metastases will be allowed if the brain metastases have been stable without steroid treatment for at least 2 weeks (radiotherapy or surgery)
Participants with primary central nervous system (CNS) tumors, or with CNS metastases as the only site of active disease (Participants with controlled brain metastases; however, will be allowed to enroll)
Subjects with inactive central nervous system (CNS) metastasis are eligible; inactive CNS metastasis is defined as: no signs of cerebral edema after successful definitive treatment of brain metastases (surgical resection, whole brain irradiation, stereotactic radiation therapy, or a combination of these) with stable or improved radiographic appearance on magnetic resonance imaging (MRI) scan at least 1 month after completion of treatment
Subjects with a history of central nervous system (CNS) metastases must have documentation of stable or improved brain imaging for at least 2 weeks after completion of definitive treatment and within 2 weeks prior to first dose of Study Drug, off or on a stable dose of corticosteroids. Definitive treatment may include surgical resection, whole brain irradiation, and/or stereotactic radiation therapy. (Applicable to tumor types of non-CNS primary origin only)
Active brain metastases (e.g., stable for < 2 weeks, symptomatic, no adequate previous treatment, requiring treatment with anti-convulsants); dexamethasone therapy will be allowed if administered as stable or decreasing dose for at least 3 weeks before randomization otherwise no steroids to exceed prednisone 10 mg/day prior to starting trial treatment; symptomatic or uncontrolled central nervous system (CNS) metastasis
Central nervous system (CNS) metastases, unless previously treated by either radiation therapy and/or surgical resection, clinically stable for at least 60 days and off corticosteroids; patients with a history of CNS metastases that are both treated and stably controlled are eligible if all of the following apply: therapy has been administered\r\n(surgery and/or radiation therapy); there is no additional treatment planned for brain metastases; the patient is clinically stable; the patient is off corticosteroids
Active central nervous system (CNS) metastasis; NOTE: Patients with prior brain metastases that are asymptomatic without corticosteroid use and stable or improved >= 90 days after treatment with surgery or radiation are not excluded
Patients with untreated brain metastases; treated brain metastases with radiation or surgery are allowed if: =< 3 cm in size AND =< 4 in number AND there is no evidence of progressive disease, on brain imaging >= 28 days after last day of central nervous system (CNS) treatment
Any approved anticancer therapy for treatment purpose is not allowed, or need to be stopped at least 2 weeks prior to initiation of study treatment; however, the following are allowed: a. endocrine therapy (selective estrogen receptor modulator [SERM], aromatase inhibitor, fulvestrant) b. palliative radiotherapy for bone metastases > 1 week prior to study treatment c. stable brain metastasis and asymptomatic treated central nervous system (CNS) metastases are allowed, patient must show stable disease by CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroids
Subjects with a history of known central nervous system (CNS) metastases must have documentation of stable or improved brain imaging for at least 2 weeks after completion of definitive treatment; definitive treatment may include surgical resection, whole brain irradiation, and/or stereotactic radiation therapy
Patients with symptomatic brain metastases are excluded; patients with asymptomatic and treated central nervous system (CNS) metastases may participate in this trial; the patient must have completed any prior treatment for CNS metastases > 28 days prior to study entry including radiotherapy or surgery; steroids for the treatment of brain metastasis are not permitted, and patients must be stable off steroid treatment for 4 weeks prior to enrollment
Subjects with previously treated brain or central nervous system (CNS) metastases are eligible provided that the subject has recovered from any acute effects of radiotherapy and is not requiring steroids, and any whole brain radiation therapy was completed at least 4 weeks prior to study drug administration, or any stereotactic radiosurgery was completed at least 2 weeks prior to study drug administration; liver metastases will not be included as part of the radiated lesions to be treated
Symptomatic brain metastases or meningeal tumors or other uncontrolled metastases in the central nervous system (CNS) unless the patient\r\n* Is > 6 months from definitive therapy,\r\n* Has a negative imaging study within 4 weeks before study entry (informed consent form [ICF] signature for full study) and\r\n* Is clinically stable with respect to the tumor at the time of study entry
Active central nervous system (CNS) disease; history of CNS metastases or cord compression is allowable if the patient has been clinically stable for at least 4 weeks since completion of definitive treatment and is off systemic steroids; in the case of brain metastases, the patient must have stable or improved imaging at least 4 weeks after completion of definitive treatment; if there is evidence of active leptomeningeal disease, the patient is ineligible
Current untreated brain metastasi(e)s; if treated history of central nervous system (CNS) metastases, should have completed radiation or surgery at least 12 weeks prior and off systemic corticosteroids
Progressive or symptomatic central nervous system (CNS) metastases; patients with known brain metastasis must have stable disease following treatment surgery, radiation, or both
mCRPC EXPANSION COHORT: Patients with evidence of CNS metastasis or leptomeningeal disease within 1 year prior to enrollment will be excluded from this clinical trial; patients with a remote history of brain metastases may be considered if they received sterilizing therapy to the CNS (resection or radiation) and have been CNS progression-free for the 1-year period; baseline imaging to rule out brain metastases is not required for screening, but should be performed prior to study enrollment if clinically indicated
Patients with a history of central nervous system metastasis are allowed provided they have been treated (i.e., surgery, radiation, and/or radiosurgery) at least 4 weeks prior to registration and have stable neurologic function, including no requirement for medication(s) to control symptoms for at least 2 weeks; patients with known leptomeningeal disease are not eligible; NOTE: Stable low dose dexamethasone allowed at discretion of protocol chair
Patients with untreated central nervous system (CNS) metastases; patients with treated brain metastases are eligible if they are clinically stable with regard to neurologic function, off steroids after cranial irradiation (whole brain radiotherapy, focal radiotherapy, and stereotactic radiosurgery) ending at least 2 weeks prior to randomization, or after surgical resection performed at least 28 days prior to randomization; the patient may have no evidence of grade >= 1 CNS hemorrhage based on pretreatment MRI or IV contrast CT scan (performed within 21 days before randomization)
History of clinically manifested central nervous system (CNS) metastases, except if brain metastases have been treated, are stable and are asymptomatic
Primary central nervous system (CNS) malignancies or CNS metastases, including leptomeningeal metastases, are not allowed; subjects with previously treated brain metastases will be allowed if the brain metastases have been stable for at least 3 months following prior treatment (radiotherapy or surgery)
Active central nervous system (CNS) malignant disease in subjects with a history of CNS malignancy. Subjects with stable, prior or currently treated brain metastases are allowed.
Subjects with brain metastases are eligible if treated (whole brain radiotherapy, stereotaxic radiotherapy, surgery) and have no symptoms (except for signs and symptoms related to central nervous system therapy) for at least 2 weeks before initiation of allocated treatment and are not taking any forbidden medications.
At screening, patients with =< 3 CNS metastases and each =< 1 cm size that were treated with either surgical resection and/or radiation therapy may be included; patients may be included if the largest lesion is =< 1 cm, and there is no evidence of progressive CNS disease on brain imaging at least 30 days after definitive treatment, and if the patients with CNS metastases are not taking prednisone > 10 mg or equivalent daily
Patients with symptomatic brain metastases are excluded; patients with asymptomatic and treated central nervous system (CNS) metastases may participate in this trial; the patient must have completed any prior treatment for CNS metastases > 28 days prior to study entry, including radiotherapy or surgery; steroids for the treatment of brain metastasis are not permitted
Subject has uncontrolled metastases to the central nervous system (CNS) based on head CT or MRI. Subjects with brain metastases may be eligible 2 weeks after definitive therapy to all known sites of CNS disease provided they are asymptomatic and either off or on a non-increasing dose (in last 2 weeks) of systemic steroids and not on anticonvulsants for seizure activity directly related to progressive CNS metastases.
PHASE I STUDY ELIGIBILITY CRITERIA:\r\nPatients with evidence of central nervous system (CNS) metastasis, spinal cord compression, or leptomeningeal disease within one year prior to enrollment will be excluded from this clinical trial; patients with a remote history of brain metastases may be considered if they received sterilizing therapy to the CNS (resection or radiation) and have been CNS progression-free for the 1-year period; baseline imaging to rule out brain metastases is not required for screening, but should be performed prior to study enrollment if clinically indicated
Subject has known active central nervous system (CNS) involvement; the subject has untreated brain or meningeal metastases; computed tomography (CT) scans are not required to rule out brain or meningeal metastases unless there is a clinical suspicion of central nervous system disease; subjects with treated brain metastases that are radiographically or clinically stable for at least 4 weeks after therapy and have no evidence of cavitation or hemorrhage in the brain lesion(s) are eligible, providing that they are asymptomatic, and do not require corticosteroids (must have discontinued steroids at least 1 week prior to study drug administration)
Active central nervous system (CNS) malignant disease in subjects with a history of CNS malignancy. Subjects with stable, prior, or currently treated brain metastases are allowed.
Participants with known central nervous system (CNS) primary tumors or metastases who have completed brain therapy (such as radiotherapy, stereotactic radiosurgery, or surgical resection) and have remained clinically stable, asymptomatic, and off of steroids for 2 weeks prior to Cycle 1 Day 1 will be eligible.
Untreated central nervous system metastases; patients are eligible if they are clinically stable, off all steroids after cranial irradiation (whole brain radiation therapy, focal radiation therapy, stereotactic radio surgery) ending at least 2 weeks prior to enrollment, or after surgical resection performed at least 2 weeks prior to enrollment
Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases
Active central nervous system (CNS) metastases; magnetic resonance imaging (MRI) (or computed tomography [CT]) required within 3 months of starting treatment for all tumor types known to commonly metastasize to the brain (i.e. all tumors except pancreas, colorectal, ovarian) and for all patients with CNS symptoms that may represent CNS metastases; metastases which have been treated with radiotherapy > 2 months prior to start of protocol therapy and are asymptomatic (off steroid therapy for at least 1 month) may be included; patients must have had normal or stable (if treated, no new lesions) brain imaging (CT or MRI) within the two months prior to day 1 of study drug\r\n* For the NSCLC expanded cohort only: radiation =< 14 days prior to day 1 of study drug; subjects must be off steroids for > 14 days prior to day 1 of study drug and anticonvulsants must be discontinued
Has CNS Disease: Participants with brain or subdural metastases are not eligible unless the metastases are asymptomatic and do not require treatment or have been adequately treated by local therapy (eg, surgery or radiotherapy) and have discontinued the use of corticosteroids for this indication for at least 4 weeks prior to study drug administration. Confirmation of radiographic stability must be done by comparing the brain scan (CT or MRI) performed during the Screening Period, using the same imaging modality, to a brain scan performed earlier (and following local therapy where applicable). Participants must be clinically stable. It is not the intention of this protocol to treat participants with active brain metastases. Note: CNS imaging is required to confirm eligibility for participants with a known history of CNS disease.
Patients with active, untreated central nervous system (CNS) metastases will be excluded from this clinical trial; patients who have brain metastases that been treated with radiation therapy or surgery will be required to have a washout period of at least 3 weeks prior to study entry, must be neurologically asymptomatic, and must not require systemic steroids
Previously untreated brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if therapy was completed at least 3 weeks previously and there is no evidence of central nervous system disease progression, mild neurologic symptoms, and no requirement for chronic corticosteroid therapy.
Patients with known CNS metastases (Patients with any clinical signs of CNS metastases must have a CT or MRI of the brain to rule out CNS metastases in order to be eligible for participation in the study). Patients who have had brain metastases treated with radiotherapy or surgically removed with no residual disease confirmed by imaging; patients should be clinically stable and off corticosteroid treatment at least 3 weeks prior to randomization).
Patients with untreated brain metastases are excluded; however, patients with metastatic central nervous system (CNS) tumors may participate in this trial, if the patient is > 4 weeks from therapy completion (including [incl.] radiation and/or surgery), is clinically stable at the time of study entry and has been on a stable dose of low dose steroids (=< 2 mg decadron per day) for at least 2 weeks
Untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressed.
Untreated brain or central nervous system (CNS) metastases or brain or CNS metastases that have progressed as per protocol-defined criteria.
Patients with treated stable CNS metastases that are asymptomatic (including leptomeningeal carcinomatosis) are allowed, if there is no evidence of progression for at least 4 weeks after CNS-directed treatment as ascertained by clinical examination and brain imaging. Patients requiring steroids must be at a stable or decreasing dose (?10 mg/day dexamethasone or equivalent) for at least 2 weeks prior to the start of treatment. The use of seizure prophylaxis is allowed.
In patients with central nervous system (CNS) metastases, metastases must be asymptomatic at the time of day 1 of the study and meet the following criteria: \r\n* Brain metastases should have been treated with either whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS)/gamma-knife, or surgical resection; \r\n* At least 28 days without progression of CNS metastases as evidenced by magnetic resonance imaging (MRI) or CT from last day of treatment with radiation to the CNS metastases; \r\n* At least 3 months from surgical resection (if had surgery) with stability on MRI brain at enrollment; \r\n* At least 14 days since last dose of corticosteroids; \r\n* Must not have leptomeningeal disease or cord compression
Patients with spinal cord compression or a history of leptomeningeal carcinomatosis. At the time of day 1 of the study, patients with central nervous system metastases must have been treated and must be asymptomatic and meet the following criteria. 1. No concurrent treatment, inclusive of, but not limited to, surgery, radiation, and/or corticosteroids. (Note: patients are allowed on systemic steroids unless these are being administered to manage central nervous system metastases); 2. Neurologic stability (lack of signs or symptoms greater than baseline prior to radiotherapy) until the time of dosing of MEDI0457; 3. For radiation treatment, patients must be: at least 14 days between last day of stereotactic radiosurgery or gamma-knife treatment and day 1 of protocol treatment, at least 28 days between last day of whole brain radiation therapy and day 1 of protocol treatment, and/or at least 14 days since last dose of corticosteroids and day 1 of protocol treatment.
Untreated brain metastases or neurologically unstable central nervous system (CNS) metastases (CNS metastases will be considered stable if there are no new nor enlarging lesions for one month, and the patient remains off steroids and anti-epileptics for the same time period)
Patients are ineligible if they have any currently active central nervous system (CNS) metastases; patients who have treated brain metastases (with either surgical resection or stereotactic radiosurgery) that have been stable on head magnetic resonance imaging (MRI) or contrast computed tomography (CT) scan for at least 4 weeks following treatment and within 4 weeks prior to randomization are eligible; patients must not have taken any steroids =< 14 days prior to randomization for the purpose of managing their brain metastases; patients with only whole brain irradiation for treatment of CNS metastases will be ineligible
Patients with central nervous system (CNS) metastases must be stable after therapy for CNS metastases (such as surgery, radiotherapy or stereotactic radiosurgery) for at least 3 months and must be off steroid treatment prior to study enrollment
Patients with a history of central nervous system (CNS) metastases must have documentation of stable or improved status based on brain imaging for at least 2 weeks after completion of definitive treatment and within 2 weeks prior to first dose of study drug, off or on a stable dose of corticosteroids
Patients must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to Step 2 re-registration; patient must not have leptomeningeal disease, spinal cord compression or brain metastases unless: (1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 14 days following treatment and prior to re-registration, AND (2) patient has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to re-registration
Patients must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to Step 2 Re-registration; patient must not have leptomeningeal disease, spinal cord compression or brain metastases unless: (1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 14 days following treatment prior to re-registration, AND (2) patient has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to re-registration
Patients must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to step 2 re-registration; patient must not have leptomeningeal disease, spinal cord compression or brain metastases unless: (1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 14 days following treatment and prior to re-registration, AND (2) patient has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to re-registration
Subjects with previously treated brain metastases who are free of central nervous system (CNS) symptoms and are > 3 months from treatment of brain metastases are eligible
Stage 1 solid tumor and stage 2 endometrial and ovarian cancer participants with known central nervous system (CNS) metastatic lesions which are symptomatic and/or growing; patients previously treated for these conditions that are asymptomatic in the absence of corticosteroid therapy are allowed to enroll; brain metastasis must be stable for 1 month with verification by imaging (brain MRI completed at screening demonstrating no current evidence of progressive brain metastases); CNS imaging will not be mandated for asymptomatic patients with no history of CNS metastases
Extradural masses that have not invaded the brain parenchyma or parameningeal tumors without evidence for leptomeningeal spread will not render the patient ineligible; patients with previous central nervous system (CNS) tumor involvement that has been treated and is stable for at least 6 weeks following completion of therapy are eligible; patients who are clinically stable as evidenced by no requirements for corticosteroids, no evolving neurologic deficits and no progression of residual brain abnormalities without specific therapy, are eligible one week post radiation or radiosurgery; patients with asymptomatic sub-centemeric CNS lesions will be eligible if no immediate radiation or surgery indicated
Patients must have no clinical evidence of active brain metastasis; patients with a history of brain metastases must have had them treated greater than 4 weeks previously with the central nervous system (CNS) lesions confirmed to be stable or regressing on imaging since the time of the last CNS treatment; patients will be evaluated with a head CT or MRI within 4 weeks of enrollment; patients must have no residual neurologic symptoms while taking either no steroids or a stable dose of steroids for the 2 weeks prior to enrollment; patients are allowed to be on a stable dose of anti-seizure meds
At screening, patients with CNS metastases treated with either surgical resection and/or radiation therapy may be included; patients may be included if the largest lesion is =< 1 cm, and there is no evidence of progressive CNS disease on brain imaging at least 28 days after treatment
Patients with treated CNS metastases > 1 cm or > 3 in number will be excluded if there is evidence of progressive CNS disease on brain imaging at least 90 days after treatment with surgery and/or radiation therapy
At screening, patients with =< 3 treated CNS metastases treated with either surgical resection and/or radiation therapy may be included; patients may be included if the largest lesion is =< 1 cm, and there is no evidence of progressive CNS disease on brain imaging at least 28 days after treatment
Patients with treated CNS metastases > 1 cm or > 3 in number will be excluded if there is evidence of progressive CNS disease on brain imaging at least 90 days after treatment with surgery and/or radiation therapy
Subjects with untreated or uncontrolled brain metastases or evidence of leptomeningeal disease; brain metastases that have been appropriately treated with radiation and/or surgery will be allowed as long as the central nervous system (CNS) disease has been stable for at least 4 weeks post-treatment
Patients with active central nervous system (CNS) metastases are excluded; patients with CNS metastases that have been treated must be off steroid treatment for > 2 months and be asymptomatic; patients that have symptoms to suggest CNS metastases should have a brain magnetic resonance imaging (MRI) within 28 days of enrollment to confirm the absence of CNS metastases; contrast computed tomography (CT) is acceptable for patients who are unable to undergo a brain MRI
Patients with untreated symptomatic brain metastases are excluded; however, patients with metastatic central nervous system (CNS) tumors may participate in this trial, if the patient is > 4 weeks from therapy completion (including radiation and/or surgery), is clinically stable at the time of study entry and is not receiving corticosteroid therapy for the brain metastases (mets)
Patients must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to registration; patient must not have symptomatic brain metastases or evidence of leptomeningeal carcinomatosis; patients with asymptomatic brain metastases are eligible if off of steroids for at least 7 days prior to registration without development of symptoms
Progressive or symptomatic central nervous system (CNS) metastases; patients with known brain metastasis must have stable disease following treatment with surgery, radiation or both; in addition, they must be off corticosteroids
Subjects with a history of central nervous system (CNS) metastases must have documentation of stable or improved status based on brain imaging for at least 2 weeks after completion of definitive treatment and within 2 weeks prior to first dose of Study Drug, off or on a stable dose of corticosteroids.
Patients with known central nervous system (CNS) metastases must have stable disease off steroids after treatment with surgery or radiation therapy
Untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressed
Known CNS metastases or leptomeningeal disease: For Part 1, patients with CNS metastases treated with whole brain radiotherapy, gamma knife, and/or surgery who are considered stable by CNS imaging and are not being treated with corticosteroids 6 weeks prior to study day 1 may be enrolled. For Part 2, patients with CNS metastases treated stereotactic radio-surgery (SRS), and/or surgery who are considered stable by CNS imaging for at least 2 months prior to enrollment and are not being treated with corticosteroids 6 weeks prior to study day 1 may be enrolled.
Known brain metastases or CNS cancer unless adequately treated with radiotherapy and/or surgery and stable by symptoms and radiographic imaging and not requiring corticosteroids for at least 2 mo before randomization
Patients with brain metastases are ineligible; all patients must have a pretreatment CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to registration
Patients must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to RE-TREATMENT registration; patient must not have leptomeningeal disease, spinal cord compression or brain metastases unless: metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 14 days following treatment and prior to RE-TREATMENT registration, AND patient has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to RE-TREATMENT registration
Patients with a history of treated brain metastases should be clinically stable for ? 4 weeks prior to signing the informed consent. Glucocorticoid therapy for central nervous system (CNS) edema is permitted if ? 20 mg of prednisolone (or equivalent).
Patients with active central nervous system (CNS) disease or history of brain metastases (mets) are excluded from study
Symptomatic or untreated central nervous system metastases requiring concurrent treatment, including but not limited to surgery, radiation, and/or corticosteroids; if treated, patient must be asymptomatic for 3 months prior to study entry.
Subjects with active central nervous system (CNS) disease are excluded; patient with brain metastases previously treated with surgery or radiation therapy and with confirmed stable disease (SD) for >= 3 weeks are allowed
Participants with a history of central nervous system (CNS) metastases prior to the initiation of first-line platinum-based chemotherapy must have received definitive local treatment and have documentation of stable or improved CNS disease status
Known active or suspected brain or leptomeningeal metastases. CNS imaging is not required prior to study entry unless there is a clinical suspicion of CNS involvement. Patients with stable, treated brain metastases are eligible provided there is no evidence of CNS disease growth on imaging for at least 8 weeks following radiation therapy or other locoregional ablative therapy to the CNS.
Subjects with active central nervous system (CNS) disease are excluded; patient with brain metastases previously treated with surgery or radiation therapy and with confirmed stable disease (SD) for >= 2 weeks are allowed
History of central nervous system (CNS) metastases unless previously treated and stable for > 8 weeks prior to study initiation
Participant with uncontrolled or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis Participants with controlled and asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior treatment for CNS metastases (must include radiotherapy and/or surgery) ? 28 days (? 14 days for stereotactic radiosurgery) and, if on corticosteroid therapy, should be receiving a stable dose of no greater than 4 mg/d dexamethasone (or equivalent anti-inflammatory potency of another corticosteroid) for at least 14 days before start of study treatment). Patients must not be receiving corticosteroids for brain metastases.
History of brain metastases; EXCEPTION: patients with a solitary brain metastasis that has been completely resected, and who have no ongoing central nervous system (CNS) symptoms and an MRI documenting no evidence of CNS disease at least 3 months after resection and within 30 days of registration, are eligible for treatment
Uncontrolled central nervous system (CNS) metastases, including leptomeningeal metastases, are not allowed; subjects with previously treated brain metastases will be allowed if the brain metastases have been stable without steroid treatment for at least 4 weeks following prior treatment (radiotherapy or surgery)
Any history of or current central nervous system (CNS) metastases. Baseline imaging of the brain is required within 28 days prior to randomization
Patients with untreated brain metastases are excluded; however, patients with metastatic central nervous system (CNS) tumors may participate in this trial, if the patient is > 4 weeks from therapy completion (incl. radiation and/or surgery), is clinically stable at the time of study entry and is receiving low dosage corticosteroid therapy
Subjects with radiographically stable Central nervous system (CNS) metastases, defined as radiographically stable on the previous 2 brain imaging scans, asymptomatic, and off systemic steroids and anticonvulsants for at least 1 month are eligible; treatment with prophylactic anticonvulsants is permitted unless listed under Prohibited Medications
Symptomatic brain metastasis or leptomeningeal disease requiring radiation therapy or escalating doses of steroids; patients with clinically stable brain metastases (previously treated or untreated) are eligible; patients in expansion cohort A must have at least one untreated central nervous system (CNS) lesion
Patients with central nervous system disease are eligible for enrollment if they have received prior radiotherapy or surgery to sites of CNS metastatic disease and are without evidence of clinical progression for at least 4 weeks prior to screening, have no evidence of new or enlarging brain metastases, and are off steroids for at least 7 days before first dose of pembrolizumab.
Patients with untreated central nervous system disease. Patients with controlled treated CNS lesions who have undergone surgery or stereotactic radiosurgery and stable for 4 weeks are eligible.
Have central nervous system (CNS) metastases (unless the patient has completed successful local therapy for CNS metastases and has been off corticosteroids for at least 4 weeks before starting study therapy); brain imaging is required in symptomatic patients to rule out brain metastases, but is not required in asymptomatic patients
Participants with known and untreated brain metastases are excluded; note: patients without known prior central nervous system (CNS) metastases and without clinical signs and symptoms of CNS involvement are not required to have a magnetic resonance imaging (MRI) of the brain prior to enrollment; patients with treated brain metastases that are asymptomatic and clinically stable for two weeks will be eligible for protocol participation
Patients with symptomatic brain or spinal cord metastases or requiring steroid therapy and patients with leptomeningeal disease; patients with treated and stable central nervous system (CNS) metastasis for 3 months or more, off steroids are eligible for the study; no major surgery or radiation therapy within 21 days before starting treatment
History of central nervous system (CNS) metastasis; Note: participants without clinical signs and symptoms of CNS involvement are not required to have magnetic resonance imaging (MRI) of the brain; (exception: participants with treated brain metastases who are asymptomatic, not currently on steroid therapy, and clinically stable for >= 2 weeks will be eligible for protocol participation)
Untreated central nervous system metastases; patients are eligible if they are clinically stable, off all steroids after cranial irradiation (whole brain radiation therapy, focal radiation therapy, stereotactic radio surgery) ending at least 2 weeks prior to enrollment, or after surgical resection performed at least 2 weeks prior to enrollment
Brain metastases (unless stable disease >3 mos. by scan without additional CNS-directed therapy)
Patients with brain metastases may participate if they have undergone appropriate treatment for the lesion(s), are at least two weeks post treatment without evidence for post-treatment progression, have no significant neurologic symptoms, and no longer require steroids for the reason of brain metastases; patients with symptoms suggestive of central nervous system (CNS) metastases should be evaluated with imaging prior to study participation
Active central nervous system (CNS) disease\r\n* Subjects with a history of CNS metastases or cord compression are allowable if they have been clinically stable for at least 6 weeks since completion of definitive treatment, are off steroids (if the steroids were part of the CNS disease treatment), and in the case of brain metastases, have stable or improved imaging at least 6 weeks after completion of their definitive treatment
Subjects with inactive central nervous system (CNS) metastasis are eligible; inactive CNS metastasis is defined as: no signs of cerebral edema after successful definitive treatment of brain metastases (surgical resection, whole brain irradiation, stereotactic radiation therapy, or a combination of these) with stable or improved radiographic appearance on magnetic resonance imaging (MRI) scan at least 1 month after completion of treatment
Known central nervous system (CNS) disease, except for treated brain metastasis; Note: treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS); gamma knife, linear accelerator (LINAC), or equivalent or a combination as deemed appropriate by the treating physician; patients with CNS metastases treated by neurosurgical resection or brain biopsy performed =< 3 months prior to randomization will be excluded; Note: craniotomy or intracranial biopsy site must be adequately healed, free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of randomization; study treatment should be initiated > 28 days following the last surgical procedure (including biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity)
Patients with central nervous system (CNS) progression are ineligible until this CNS progression is treated either with whole brain radiation or stereotactic radiosurgery (SRS) and have an magnetic resonance imaging (MRI) of the affected CNS lesion(s) 3 months after radiation therapy (per National Comprehensive Cancer Network [NCCN] guidelines) demonstrating stable (or improved) disease prior to proceeding with enrollment on the AVX901 study; patients also must be off all steroids prior to initiating the AVX901 protocol
Subjects with known central nervous system (CNS) metastases must have received whole-brain radiation or other appropriate therapy not less than 4 weeks prior to starting the study drug, and exhibit clinical stability of brain disease as judged by the treating physician
Patients with a history or evidence of central nervous system (CNS) disease, including brain tumor, seizures not controlled with standard medical therapy or any brain metastases
Patients with evidence or history of central nervous system (CNS) metastases or spinal cord compression, unless prior treatment with surgery or radiotherapy AND no progression of CNS disease within 6 months prior to treatment
Brain metastases permitted in Arms A and B if:\r\n* Central nervous system (CNS)-directed treatment has been given\r\n* No CNS-directed therapy for the past 3 months, including glucocorticoids AND\r\n* CNS disease has been clinically and radiographically stable for at least 8 weeks
Brain metastases permitted in Arms C and D if:\r\n* CNS-directed treatment has been given\r\n** >= 4 weeks interval between whole brain radiation therapy and initiation of protocol-based therapy\r\n** >= 2 weeks interval between stereotactic radiosurgery or gamma knife (or equivalent) and initiation of protocol-based therapy\r\n* CNS disease has been clinically and radiographically stable for at least 4 weeks\r\n* In Arm C, if patient on glucocorticoids, must be on stable (4 weeks) dose of no more than 2 mg/day of dexamethasone or equivalent\r\n* In Arms B and D, no steroids are allowed
Patients must not have known central nervous system (CNS) metastases or leptomeningeal disease; screening with brain imaging is not required for asymptomatic patients
Participants with active brain metastases; stable treated brain metastases are allowed (this includes participants who have documented radiologic stability at least 4 weeks after radiotherapy, and do not require systemic steroids for management of symptoms from central nervous system [CNS] metastatic lesions)
Central nervous system (CNS) inclusion criteria:\r\n* Subjects without CNS metastases are eligible; Note: brain imaging is not required for asymptomatic subjects without known brain metastatic disease prior to enrollment into the study\r\n* Subjects with untreated asymptomatic CNS metastases not needing immediate local therapy in the opinion of investigator are eligible; for subjects with untreated asymptomatic CNS lesions > 2.0 cm magnetic resonance imaging (MRI), discussion with and approval from the lead principle investigator (PI) is required prior to enrollment\r\n* Subjects with stable brain metastases previously treated with radiation therapy or surgery are allowed to enroll, provided that they are off corticosteroids or on stable/tapering dose of corticosteroids and stability of CNS metastatic disease for at least 4 weeks has been demonstrated, with the last MRI taken within 2 weeks prior to cycle 1 day 1 of the study; relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions
Active central nervous system metastases. Patients with a history of brain metastases may be eligible, provided they have been definitively treated and are clinically stable, after discussion with sponsor. Treated or untreated leptomeningeal disease is not permitted.
Participants with central nervous system (CNS) metastases are not eligible, unless they have completed local therapy (eg, whole brain radiation therapy (WBRT), surgery or radiosurgery) and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs (eg, radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment
Subject has symptomatic central nervous system (CNS) metastasis. Subject with previously treated brain or CNS metastases are eligible provided that the subject has recovered from any acute effects of radiotherapy, does not have brain metastasis related symptoms, is not requiring systemic steroids for at least 2 weeks prior to study drug administration, and any whole brain radiation therapy was completed at least 4 weeks prior to study drug administration, or any stereotactic radiosurgery (SRS) was completed at least 2 weeks prior to study drug administration. Steroid inhaler use or ointment treatment for other concomitant medical disease is permitted.
Patients with known brain metastases diagnosed within 1 year will be excluded from this clinical trial; exception: patients with brain metastases diagnosed greater than 1 year prior to study entry may be considered if they received sterilizing therapy to the central nervous system (CNS) (resection or radiation) and have been CNS progression-free for the 1-year period
Subject has symptomatic central nervous system (CNS) metastasis. Subject with previously treated brain or CNS metastases is eligible provided that the subject has recovered from any acute effects of radiotherapy and is not requiring systemic steroids and any whole brain radiation therapy was completed at least 2 weeks prior to study drug administration, or any stereotactic radiosurgery was completed at least 1 week prior to study drug administration.
Patients with untreated brain metastases are excluded; however, patients with metastatic central nervous system (CNS) tumors may participate in this trial, if the patient is > 4 weeks from therapy completion (including radiation and/or surgery), is clinically stable at the time of study entry and is not receiving corticosteroid therapy
Patients with known active brain metastases; patients with a history of treated brain metastasis are eligible if the patient is off systemic steroids and there are no clinical indications of central nervous system (CNS) progression for a least 1 month; patients with glioblastoma multiforme are eligible if the above criteria are otherwise met; note: many clinical trials do not allow enrollment of such patients; if the physician, in good conscience, feels that applicable protocols for their patient do exist, enrollment onto this trial is acceptable, assuming other eligibility criteria are met
Evidence of spinal cord compression or current evidence of CNS metastases. Screening CT/MRI of the brain is mandatory. Note: Patients who have been treated for CNS metastases by radiation or gamma knife surgery, who been stable for at least 2 months and have discontinued high dose corticosteroids will be eligible for protocol participation
Patients with brain metastases unless all of their metastatic brain lesions have been resected or treated with stereotactic radiotherapy with gamma rays and they are off corticosteroids; patient should not have significant brain edema; patients with spinal cord compression and leptomeningeal disease; patients with treated central nervous system (CNS) metastases are not eligible for the neoadjuvant treatment cohort in Phase II; no major surgery or radiation therapy within 21 days before starting treatment
Patients having Central Nervous System (CNS) metastases. Patients who have had brain metastases surgically removed or irradiated with no residual disease confirmed by imaging are allowed
Known central nervous system (CNS) disease, except for those participants with treated brain metastasis who are stable for at least 1 month, having no evidence of progression or hemorrhage after treatment and no ongoing requirement for corticosteroids, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period.
Brain metastases are excluded unless treated and shown to be controlled more than 1 month from after craniotomy or more than 2 weeks after gamma knife radiosurgery and not associated with central nervous system (CNS) symptoms
Patients must not have received prior anticancer treatment for metastatic disease (for example, but not limited to, systemic, local, radiation, radiopharmaceutical). -Exceptions: Surgery for melanoma and/or postresection brain radiotherapy (RT) if central nervous system (CNS) metastases and/or prior treatment with adjuvant interferon (IFN) (as described in Exclusion Criterion 2).
Subject has symptomatic central nervous system (CNS) metastases or leptomeningeal involvement as assessed through medical history review and physical examination. Subject with prior brain metastases must:
Symptomatic or untreated central nervous system metastases requiring concurrent treatment, including but not limited to surgery, radiation, and/or corticosteroids; if treated, subject must be asymptomatic for 3 months prior to study entry
Uncontrolled central nervous system (CNS) metastases are not allowed; subjects with previously treated brain metastases will be allowed if the brain metastases have been treated, toxicities have resolved to grade 1 or baseline and steroids are no longer required; leptomeningeal metastases are not allowed
Subjects with asymptomatic brain metastases or other central nervous system (CNS) disease at screening/diagnosis are eligible
Subjects with active central nervous system (CNS) disease are excluded; patient with brain metastases previously treated with surgery or stereotactic radiosurgery and with confirmed stable disease (SD) for >= 2 weeks are allowed
Central nervous system metastases\r\n* Note: Subjects with previously treated (radiotherapy or surgery) brain metastasis that have been stable without steroid treatment for at least 3 months following prior treatment may be enrolled
For patients with brain metastases, the following criteria must be met: Previously untreated brain metastases that are asymptomatic and not requiring steroids are permitted. Previously treated brain metastases are permitted if most recent CNS radiographic imaging demonstrates no evidence of CNS disease progression For patients with previously untreated brain metastases, Central Nervous System (CNS) imaging is required at the time of disease imaging throughout treatment.
Symptomatic, untreated, or uncontrolled central nervous system (CNS) metastases or seizure disorder; patients with asymptomatic CNS metastases treated with whole brain radiation (WBRT) or gamma knife radiosurgery (GKR) may be enrolled >= 1 week after completion of WBRT/GKR provided toxicities are =< Common Toxicity Criteria (CTC) grade I at the time of registration and/or controlled with dexamethasone =< 2 mg once daily for at least 5 days at the time of study treatment; patients with symptomatic CNS metastases treated with WBRT/GKR may be enrolled >= 2 weeks after completion of WBRT/GKR provided toxicities are =< CTC grade 1 at the time of registration and neurologic symptoms controlled with dexamethasone =< 2 mg once daily for at least 1 week at the time of study treatment
The subject has uncontrolled metastases to the central nervous system (CNS). Subjects with brain metastases are eligible provided they have shown clinical and radiographic stable disease for at least 28 days after definitive therapy and have not received prior whole brain radiation (Phase 1 only).
For subjects with solid tumors that are not primary central nervous system (CNS) tumors or NF-1 associated plexiform neurofibromas subjects with symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression are excluded. NOTE: Subjects previously treated for these conditions that have had stable CNS disease (verified with consecutive imaging studies) for >3 months, are asymptomatic and are not currently taking corticosteroids, or are on stable dose or decreasing of corticosteroids for at least 7 days prior to enrolment are permitted.
Patients with asymptomatic central nervous system (CNS) metastases will be eligible; for patients that have undergone radiation therapy for their CNS metastases, a minimum of 14 days must elapse prior to study registration, and patients must have recovered from any adverse events related to radiotherapy with the exception of alopecia and grade 1 neuropathy
Patients must be without clinical evidence of central nervous system (CNS) disease; patients with a history of treated brain metastasis must be stable with no evidence of disease for 3 months
Patients with active central nervous system (CNS) disease or history of brain metastases (mets) are excluded from study
Patients with untreated brain metastases are excluded; however, patients with metastatic central nervous system (CNS) tumors may participate in this trial, if the patient is > 4 weeks from therapy completion (including [incl.] radiation and/or surgery), is clinically stable at the time of study entry, and is not receiving corticosteroid therapy
Subjects with primary central nervous system (CNS) tumors or metastases resected or have received radiation therapy ending at least 4 weeks prior to study day 1 are eligible providing they meet all of the following criteria: a) residual neurological symptoms grade ? 1; 2) no dexamethasone treatment; and c) follow-up MRI shows no new lesions appearing
Patients with primary central nervous system tumors or brain metastases. However, if radiation therapy and/or surgery has been completed and serial evaluation by CT (with contrast enhancement) or MRI over a minimum of 3 months demonstrates the disease to be stable and if the patient remains asymptomatic, then the patient may be enrolled. Such patients must have no need for treatment with steroids or anti-epileptic medications.
Untreated central nervous system (CNS) metastases, eligible if they are clinically stable with regard to neurologic function, off all steroids after cranial irradiation at least 2 weeks prior or after surgical resection performed at least 4 weeks prior to randomization
Central nervous system (CNS) metastases: Patients who remain asymptomatic after successful definitive treatment of brain metastases (i.e., surgical resection, curative whole brain irradiation, stereotactic radiation therapy, or a combination of these) demonstrating stable or improved radiographic appearance on magnetic resonance imaging (MRI) scan >= 3 months after completion of treatment and no signs of cerebral edema are eligible
History and/or current evidence of CNS metastases. Baseline MRI scan by Independent Reviewer to confirm no brain mets;
Patients who have untreated (primary) or uncontrolled Central Nervous System (CNS) (primary or metastatic) malignancies; patients with CNS metastases who have undergone surgery or radiotherapy or who have been on a stable dose of corticosteroids for at least 2 weeks and whose disease is stable prior to the first scheduled day of dosing will be eligible for the trial.
Central nervous system (CNS) metastasis; NOTE: history of brain metastasis other than locally treatable lesions (i.e., lesions treatable with surgery or radiosurgery); patients with locally treatable disease may be considered for study if they have completed treatment without evidence of CNS progression for > 4 weeks after completion of treatment; patients with a history of brain or other CNS metastases not amenable to local therapy will not be eligible
Subject has symptomatic central nervous system (CNS) metastasis. Subject with previously treated brain or CNS metastases are eligible provided that the subject has recovered from any acute effects of radiotherapy and is not requiring steroids, and any whole brain radiation therapy was completed at least 2 weeks prior to study drug administration, or any stereotactic radiosurgery (SRS) was completed at least 1 week prior the first dose of study drug.
Any active central nervous system (CNS) lesion (i.e., those with radiographically unstable, symptomatic lesions) and/or leptomeningeal metastases; however, patient treated with stereotactic radiotherapy, whole brain radiation or surgery are eligible if patient remained without evidence of CNS disease progression >= 4 weeks; patients must be off corticosteroid therapy for >= 2 weeks
Patients with either a malignant central nervous system (CNS)-primary cancer or with brain metastases; patients do not need to undergo brain imaging unless indicated per standard workup and management (e.g. advanced stage lung cancer receiving definitive therapy)
Active untreated brain or leptomeningeal metastases; in patients with treated central nervous system (CNS) metastases, eligible if symptoms controlled for at least 4 weeks; dexamethasone allowed if total daily dose does not exceed 2 mg
Uncontrolled metastases to the central nervous system (CNS). Participants with brain metastases are eligible provided they have shown clinical and radiographic stable disease for at least 4 weeks after definitive therapy and have not used steroids for at least 4 weeks prior to first dose of ABBV-085.
Patients with known active brain metastases are excluded; patients with a history of central nervous system (CNS) metastases that have been treated must be stable with no symptoms for > 3 months after completion of that treatment and off steroid treatment, with image documentation required prior to study enrollment
With signs and/or symptoms of central nervous system cancers (e.g., tumors, metastases, leptomeningeal disease) as determined by their physician, medical records, or by a brain MRI, either at the time of enrollment or during the study period
Untreated brain or CNS metastases or brain/CNS metastases that have progressed. Subjects with previously treated and clinically stable brain/CNS metastases and who are off all corticosteroids for ? 4 weeks are eligible.
Patient has a primary neoplasm of the brain or known uncontrolled metastases to the central nervous system (CNS). Patients with brain metastases are eligible, provided they have shown clinical and radiographically stable disease for at least 4 weeks after definitive therapy and have not used steroids for at least 4 weeks prior to first dose of PRN1371.
Has known central nervous system (CNS) metastases. Patients with previously treated brain metastases may participate provided they are:
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; patients with previously treated brain metastases may participate provided:\r\n* No current brain metastasis lesion greater than 2 cm. Patients with prior metastasis lesions greater than 2 cm that have been removed by surgical and/or radiotherapy may be enrolled if the lesion has been stable since surgery or radiotherapy.\r\n* No new or progressing brain metastasis of any size.\r\n* No stereotactic radiation or craniotomy within 4 weeks of cycle 1 day 1.\r\n* They are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment.\r\n* No clinically significant symptoms secondary to brain metastases. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiological stable (i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to the first dose of trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
Active central nervous system metastases and/or carcinomatous meningitis (stable treated brain metastases not requiring steroids > 4 weeks allowed)
Known central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable without evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; the use of topical steroids is permitted
Patients with known active or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis; asymptomatic, treated, and/or stable brain metastases, as measured by subsequent radiologic evaluations at least two months apart, are permitted
Active central nervous system metastases and/or carcinomatous meningitis\r\n* Note: Patients with untreated brain metastasis will be excluded; patients with previously treated brain metastases may participate provided they meet the following criteria:\r\n** Inactive (without evidence of progression which is documented by CT or MRI within 90 days prior to registration), AND\r\n** On =< 10 mg/day prednisone or equivalent for at least 28 days prior pre-registration
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with untreated brain metastases and patients who have had brain metastases re-treated with radiation will be excluded; patients whom have either midline shift, or any signs of herniation (even if disease has been treated with GK) will be excluded; subjects with previously treated brain metastases may participate provided they are 1) stable (without clinical evidence of progression) 2) are out at least 10 days from CNS radiation and 3) and are not using steroids as part of treatment for their brain lesions for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously resected brain metastases may participate provided it has been at least 6 months and no CNS progression has been identified
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate if they are stable, and have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment
Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by magnetic resonance imaging [MRI] for at least four weeks prior to the first dose of study drug), have no evidence of new or enlarging brain metastases and are off systemic steroids (=< 10 mg/day prednisone or equivalent) for at least two weeks prior to enrollment
Has known active and untreated brain (central nervous system [CNS]) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may not participate
Has known active CNS metastases and/or carcinomatous meningitis; participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable.
Active brain metastases or carcinomatous meningitis (treated metastases are permitted, provided the patient is asymptomatic and off steroids for 28 days)
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis Note: Patients previously treated for brain metastases may be able to participate provided they are stable
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, ie, without evidence of progression for at least 4 weeks by repeat imaging.
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, ie, without evidence of progression for at least 4 weeks by repeat imaging, clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they have stable brain metastases
Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; patients with previously treated brain metastases may participate provided they are clinically stable without the use of systemic steroids for at least 8 weeks prior to study entry
Has known central nervous system (ie, brain and/or spinal cord) metastases and/or carcinomatous meningitis. Participants with brain metastases may participate only if they satisfy all of the following:
Central nervous system (CNS) metastases, with the following exception: Subjects who have previously treated CNS metastases, are asymptomatic, and have no requirement for steroids at least 14 days prior to first dose of study drug; Subjects with carcinomatous meningitis are excluded regardless of clinical stability.
Patients with known active or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis; asymptomatic, treated, and/or stable brain metastases, as measured by subsequent radiologic evaluations at least two months apart, are permitted
Central nervous system (CNS) metastases, with the following exception: • Subjects who have previously-treated CNS metastases, are asymptomatic, and have no requirement for steroids at least 14 days prior to first dose of study drug. Subjects with carcinomatous meningitis or leptomeningeal spread are excluded regardless of clinical stability.
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are clinically stable and are not using steroids for at least 7 days prior to trial treatment (stereotactic brain radiation therapy to isolated brain metastases does not require washout period providing no steroids are required)
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they have stable brain metastases and did not receive chemotherapy for metastatic breast cancer.
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (i.e., without evidence of progression by repeat imaging), clinically stable and without requirement of steroid treatment for ?14 days prior to the first dose of study drug.
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks and, have no evidence of new or enlarging brain metastases and also are off steroids 3 days prior to dosing with study medication; stable brain metastases by this definition should be established prior to the first dose of pembrolizumab
History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medications for 3 months prior to first dose of study drug; screening with CNS imaging studies (CT or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases
History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for ? 6 months prior to randomization; Note: Screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases
Have known active central nervous system (CNS) metastasis and/or carcinomatous meningitis. Participants with treated CNS metastases are eligible for this study if they have not received corticosteroids and/or anticonvulsants within 7 days of study treatment, and their disease is asymptomatic and radiographically stable for at least 60 days.
Any uncontrolled neurological symptom attributed to CNS metastasis
Symptomatic central nervous system (CNS) metastasis(es). Note: Baseline CT/MRI of the brain is required for SCLC patients enrolled in Arm 4. Patients with previously treated CNS metastasis(es) are eligible if the patients with previously treated CNS metastasis(es) are asymptomatic and radiographically/clinically stable and not requiring steroids within 4 weeks prior to first dose. Note: Non-SCLC patients without clinical signs or symptoms of CNS involvement are not required to have a computed tomography (CT)/magnetic resonance imaging (MRI) scan of the brain unless it is considered standard of care.
History or clinical evidence of central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases, unless they have been previously treated, are asymptomatic, and have had no requirement for steroids or enzyme inducing anticonvulsants in the last 14 days prior to screening
CNS metastases if not previously treated and stable for at least 2 months per imaging and clinical assessment.
Have central nervous system (CNS) metastasis with either radiotherapy or development of neurological changes ?14 days prior to receiving study treatment. Participants may be receiving a stable dose of corticosteroids. Screening of asymptomatic participants without history of CNS metastasis is not required. Untreated CNS metastases are not permitted.
Subjects with central nervous system metastasis; with the exception of subjects who have stable brain metastases as defined as off steroids and no CNS progress for 6 months after CNS treatment.
Have metastasis to the CNS that is symptomatic and/or requires therapy with corticosteroids or anti-convulsant medication. However, subjects who have completed treatment (radiation therapy) for CNS metastases and do not require continued treatment with corticosteroids or anti-convulsants may be enrolled in this study.
At least one measurable CNS metastasis, defined as ? 10 mm in at least one dimension
Patients with secondary metastasis to the CNS are eligible if they have met certain criteria.
History of unstable central nervous system (CNS) metastases or seizure disorder related to the malignancy; however, those subjects who were treated for prior CNS metastases and who are asymptomatic may participate in the study as long as they are not receiving treatment with steroids.
History of seizures, central nervous system tumors or CNS metastasis. Due to the incidence of silent CNS metastases in patients with advanced NSCLC, such patients must undergo mandatory screening with brain MRI or CT scan to determine eligibility.
Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging evaluation during screening and prior radiographic assessments; participants with a history of treated asymptomatic CNS metastases are eligible
Known or clinically suspected central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases; history or clinical evidence of CNS metastases unless they have been previously treated, are asymptomatic, and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days
Patients must not have known non-controlled CNS metastasis.
Patients with central nervous system (CNS) progression (parenchymal but not leptomeningeal) are eligible if CNS metastases are treated and deemed stable (with a repeat computed tomography [CT]/magnetic resonance imaging [MRI] imaging study) prior to the enrollment date; if radiation is used to treat CNS parenchymal disease, a 2 week washout period will apply
Central nervous system (CNS) metastases at baseline, with the exception of those subjects who have previously treated CNS metastases (surgery +/- radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: \r\n* Are asymptomatic, and \r\n* Have no requirement for steroids or enzyme-inducing anti-convulsants in the prior 28 days
Carcinomatous meningitis, untreated central nervous system (CNS) disease or symptomatic CNS metastasis. Patients with previously treated CNS metastasis (excluding carcinomatous meningitis) may participate if they are stable (without evidence of progression by imaging, using identical imaging modality at each assessment, for at least 4 weeks prior to first dose of study treatment), have no evidence of new or emerging CNS metastasis, and are not using steroids for at least 7 days prior to first dose of study treatment
Treated central nervous system (CNS) metastasis allowed if treatment is completed >= 8 weeks prior to enrollment; patients must be asymptomatic off systemic corticosteroids for at least 4 weeks after completion of radiation therapy; CNS disease must be stable or regressed on repeat imaging performed at least 4 weeks after completion of therapy
Subject has symptomatic CNS metastases. Subjects with prior history of symptomatic CNS metastasis must have received treatment and be neurologically stable for at least 1 month prior to leukapheresis and lymphodepletion.
Known or clinically suspected central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases; history or clinical evidence of CNS metastases unless they have been previously treated, are asymptomatic, and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days
Known or clinically suspected central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases; history or clinical evidence of CNS metastases unless they have been previously treated, are asymptomatic, and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days
For patients with central nervous system (CNS) metastases, metastases must be asymptomatic at the time of day 1 of the study and meet the following criteria:\r\n* At least 28 days without progression of CNS metastases as evidenced by magnetic resonance imaging (MRI) or computed tomography (CT) after last day of treatment with radiation to the CNS metastases\r\n* At least 14 days since last dose of corticosteroids\r\n* Must not have leptomeningeal disease or cord compression
Symptomatic and untreated central nervous system (CNS) metastasis; however, patients with 1 to 2 asymptomatic, less than 1 cm brain/CNS metastases without significant edema may be considered for treatment; if sub-centimeter CNS lesions are noted at study entry, then repeat imaging will be performed, if more than 4 weeks have elapsed from the last scan
Known active (untreated) central nervous system (CNS) metastases that require steroids; subjects with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 2 weeks before study entry, defined as:\r\n* No evidence of new or enlarging CNS metastasis or new neurological symptoms attributable to CNS metastases\r\n* Asymptomatic and receiving either no or stable doses of anticonvulsants and total doses of corticosteroids equivalent to 10 mg of prednisone or less
Previously untreated CNS metastasis or progressive CNS metastasis
Patients with uncontrolled central nervous system (CNS) metastasis are not eligible; patients with CNS metastases are to be stable for > 3 months after treatment and off steroid treatment prior to study enrollment
There is no evidence of new or enlarging CNS metastasis or new neurological symptoms attributable to CNS metastases.
Subjects must either have no central nervous system (CNS) metastasis, or carcinomatous meningitis, or if CNS metastasis is present, must have stable treated cerebral metastases from BC, NSCLC, RCC, CRC, GEC, or melanoma. Subjects must not have symptomatic auto-immune disease or be immunosuppressed.
Current or previously treated brain metastasis or active leptomeningeal disease; head imaging is required during screening in all patients to exclude the presence of central nervous system (CNS) metastatic disease
ALK-positive NSCLC patients with asymptomatic central nervous system (CNS) metastases who are neurologically stable or have not required increasing doses of steroids within the 2 week prior to study entry to manage CNS symptoms
Non-ALK-positive NSCLC patients with CNS metastasis should have completed a course of therapy would be eligible for the study provided they are clinically stable for 1 month prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis (2) off steroids
Patients with stable and clinically insignificant central nervous system (CNS) disease are allowed; patients must be off steroids with no new CNS symptoms or findings on radiographic imaging for 1 month
History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug; screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases
Subjects who have metastasis to the brain are eligible for IV administration; however, any CNS lesion must be inactive; prior metastasis that has been treated and is no longer present is acceptable; no metastases to the CNS (brain or spine) of non-CNS solid tumors may be injected due to the potential for swelling at the injection site
Patients with CNS metastasis at presentation will not be eligible
Known central nervous system (CNS) primary tumor, CNS metastases or carcinomatous meningitis (Part A). Patients may be enrolled with CNS metastasis in certain circumstances in Part B.
Patient untreated CNS metastases with 4 or fewer sites of disease, with no single site larger than 20mm, are eligible if they are asymptomatic and not requiring steroids at any dose. Patients with asymptomatic CNS metastases may be treated with radiosurgery before or during therapy on trial without treatment delays.
History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug; screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases
Asymptomatic or symptomatic CNS metastasis allowed
Previously-treated or untreated CNS metastasis allowed
Patients with Gilbert's disease or known CNS metastatic disease. However, patients with CNS metastases who are asymptomatic and have completed a course of therapy are eligible for the study provided that they are clinically stable for 1 month prior to entry as defined as: (1) no evidence of new enlarging CNS metastasis, (2) off steroids or on a stable dose of steroids.
Active and untreated central nervous system (CNS) metastases (including metastasis identified during screening MRI or contrast CT); patients with asymptomatic, treated metastases may be eligible if their lesion(s) have demonstrated stability over 2 months
Patients must have no history of central nervous system (CNS) metastasis at the screening assessment\r\n* NOTE: Patients with stable brain metastases (mets) which have been treated are eligible; patients with suspected symptoms of CNS metastasis should undergo CNS imaging at the time of screening to rule out active metastasis
Patients with active or untreated central nervous system (CNS) disease; patients previously treated for CNS disease must be asymptomatic and must not be using steroids for at least 4 weeks prior to starting the study treatment
Patients with a history of prior central nervous system (CNS) metastases or skull lesions with intracranial extension will be required to have a head computed tomography (CT) or magnetic resonance imaging (MRI) at study entry demonstrating no active CNS metastases; patients with skull metastases with associated intracranial soft tissue masses will remain eligible
Untreated central nervous system (CNS) metastasis; if treated CNS metastasis/es, treatment of CNS disease (surgery or radiation) must have been completed at least 30 days prior to registration; patients could still be on steroids
History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug; screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases
Participants with a history or clinical evidence of central nervous system primary tumors or metastases including leptomeningeal metastases unless they have been previously treated, are asymptomatic, and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days before screening
Have symptomatic CNS metastases (parenchymal or leptomeningeal) at screening or asymptomatic disease requiring an increasing dose of corticosteroids to control symptoms within 7 days prior to randomization.
Patients with CNS metastases that are symptomatic must have received therapy (surgery, XRT, gamma knife) and be neurologically stable and off of steroids. The patient should be off steroids at least 14 days before pre-registration. Asymptomatic CNS metastatic disease without associated edema, shift, requirement for steroids or anti-seizure medications are eligible after discussion with the sponsor medical monitor. For patients with a history of CNS metastasis, baseline and subsequent radiological imaging must include evaluation of the brain (MRI preferred or CT with contrast)
Patients with known brain metastasis are eligible only if by central nervous system (CNS) imaging there is no evidence of CNS progression at least 30 days following definitive CNS treatment (resection or radiation)
Symptomatic CNS metastasis
CNS metastasis that is symptomatic or progressing or untretaed or that required current therapy (e.g. evidence of new or enlarging CNS metastasis or new neurological symptoms attributable to CNS metastases)
Have the presence of unstable central nervous system (CNS) metastasis. History of CNS metastasis or stable CNS metastases is allowed (no longer requiring active therapy such as steroid medications). Participants with a history of CNS metastases must have a brain scan (for example, magnetic resonance imaging [MRI]) within 28 days of randomization to document stability, even if there have been no changes in symptoms.
CNS metastasis except adequately treated brain metastasis documented by baseline CT or MRI scan that has not progressed since previous scans and that does not require corticosteroids for management of CNS symptoms
Asymptomatic and adequately treated CNS metastases are not exclusionary
Have symptomatic central nervous system (CNS) malignancy or metastasis. Screening of asymptomatic subjects without history of CNS metastases is not required.
PART B: Patients with CNS metastases are eligible for enrollment if they have no overt evidence of neurological deficits, and are not requiring anti-epileptics or steroids to control their neurological symptoms; patients with known CNS metastases must have relevant CNS imaging performed approximately coincident with body imaging during response assessments
No clinical evidence of central nervous system (CNS) metastases (including carcinomatous meningitis) at baseline, with the exception of those patients who have previously-treated CNS metastases (surgery +/- radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) had no requirement for steroids or enzyme-inducing anticonvulsants within 6 months prior to registration
History or evidence upon physical/neurological examination of central nervous system (CNS) disease unrelated to cancer, unless adequately treated with standard medical therapy (e.g. uncontrolled seizures); symptomatic CNS metastasis
History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to registration; screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases
History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases
Known central nervous system (CNS) metastases or leptomeningeal carcinomatosis; screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if the subject has clinical findings suggestive of CNS metastasis
Pathologically (histologically or cytologically) proven diagnosis of a non-hematopoietic malignancy other than small cell lung cancer and germ cell malignancy; direct biopsy of central nervous system (CNS) lesions is not necessarily required although could constitute an allowed site of tissue confirmation as medically prudent; patients who have been disease free for more than 5 years prior to the appearance of CNS metastases should undergo repeat biopsy of either a systemic metastasis or the CNS metastases to confirm the recurrent malignancy
Clinically unstable central nervous system (CNS) metastases (to be eligible, subjects must have stable disease ? 3 months, confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and/or have CNS metastases well controlled by low-dose steroids, anti-epileptics, or other symptom-relieving medications)
Any eligible histologic diagnosis other than desmoplastic medulloblastoma, with no evidence of CNS metastasis
Any eligible histologic diagnosis, with evidence of CNS metastasis
Patients with asymptomatic treated CNS metastasis may be enrolled after discussion with the Medical Monitor.
Patients with diagnosis of retinoblastoma with metastasis to the central nervous system (CNS) must be confirmed by an ophthalmologist and/or a pathologist; in conjunction with the pediatric oncologist; metastasis to the CNS is defined as a mass in the chiasm or other site in the CNS, confirmed by magnetic resonance imaging (MRI)\r\n* At diagnosis\r\n* At relapse after conventional therapy\r\nIt is acceptable to have other sites of metastatic disease: lymphatic, bone, bone marrow or others, but these will not be considered for response
Subject has symptomatic central nervous system (CNS) metastasis. Subjects with asymptomatic, untreated CNS metastases are allowed. Subjects with previously treated and currently asymptomatic CNS metastases are eligible provided they meet the following:
Known or clinically suspected central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases; history or clinical evidence of CNS metastases unless they have been previously treated, are asymptomatic, and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days
No evidence of new or enlarging CNS metastasis or new neurological symptoms attributable to CNS metastases.
History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for more than 1 week within 6 months prior enrollment
Patients with clinically unstable central nervous system (CNS) metastasis (to be enrolled in the study, subjects must have confirmation of stable disease by magnetic resonance imaging [MRI] or computed tomography [CT] scan within 4 weeks of the first day of study defined treatment and have CNS metastases well controlled by steroids, anti-epileptics or other symptom-relieving medications)
Patients with central nervous system (CNS) metastasis. Intrathecal chemotherapy is allowed for patients who require CNS prophylaxis or therapy.
History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, unless previously treated, asymptomatic, and off steroids and anti-seizure medication for 6 months prior to first dose of study drug
Symptomatic and untreated central nervous system (CNS) metastasis; however, patients with 1-2 asymptomatic, less than 1 cm brain/CNS metastases without significant edema may be considered for treatment; if sub-centimeter CNS lesions are noted at study entry, then a repeat imaging will be performed if more than 4 weeks have elapsed from the last scan
Have symptomatic CNS malignancy (with the exception of medulloblastoma) or metastasis.
Have symptomatic central nervous system (CNS) malignancy or metastasis (screening not required). Participants with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids and/or anticonvulsants, and their disease is asymptomatic and radiographically stable for at least 28 days.
No known central nervous system (CNS) metastases or neurological symptoms possibly related to active CNS metastasis
Symptomatic central nervous system (CNS) malignancy or metastasis. Patients with treated CNS metastases are eligible provided their disease is radiographically stable, asymptomatic, and they are not currently receiving corticosteroids and/or anticonvulsants. Screening of asymptomatic patients without a history of CNS metastases is not required
History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, unless previously treated, asymptomatic, and off steroids and anti-seizure medication for 6 months prior to first dose of study drug.
Have symptomatic central nervous system (CNS) malignancy (with the exception of medulloblastoma) or metastasis (screening not required). Patients with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids and/or anticonvulsants, and their disease is asymptomatic and radiographically stable for at least 60 days.
Histologically or cytologically confirmed non-small cell lung cancer or other “platinum responsive malignancies”, including but not limited to: esophageal cancer, ovarian cancer, germ cell malignancies, transitional cell cancer, that are not curable with chemotherapy, surgery or radiotherapy; a tissue block, 10 unstained slides or fresh tissue biopsy is required; patients with central nervous system (CNS) metastases which are symptomatic must have received therapy (surgery, XRT, gamma knife) and be neurologically stable and off steroids; patients with asymptomatic lesions without significant edema and no evidence of shift are allowed to participate without prior CNS therapy; such patients are anticipated to receive specific CNS therapy after 2-4 courses of study therapy
History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis except for subjects who have previously treated CNS metastases (surgery with or without radiotherapy, radiosurgery, or gamma knife) and meet all 3 of the following criteria:\r\n* Are asymptomatic and,\r\n* Have had no clinical evidence of active CNS metastases for >= 28 days prior to enrollment and,\r\n* Have no requirement for steroids or enzyme-inducing anticonvulsants (EIAC)
Patients may have had prior central nervous system (CNS) metastasis providing: CNS disease has been previously treated and CNS disease has been clinically stable for 4 weeks prior to study entry (assessment must be made by computed tomography [CT] or magnetic resonance imaging [MRI])
Central nervous system (CNS) metastases at baseline, with the exception of those subjects who have previously-treated CNS metastases (surgery +/- radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anticonvulsants in prior 6 monthly time interval
Have symptomatic central nervous system (CNS) malignancy or metastasis. Asymptomatic participants with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids to treat CNS metastases
Patients with central nervous system (CNS) involvement must have been treated, be asymptomatic, do not exhibit progression of CNS metastases on MRI or CT within 28 days, and do not have concurrent leptomeningeal disease or cord compression.
Patients with active central nervous system (CNS) metastasis and/or carcinomatous meningitis; however, patients with CNS metastasis (except leptomeningeal disease) who have completed a therapy and are clinically stable for 3 weeks as defined as: (1) no evidence of new or enlarging CNS metastasis and (2) off steroids and/or anticonvulsants may be eligible
Patients must not have a history or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug; screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases
Have symptomatic CNS metastasis. Patients with a history of CNS metastases who have been treated with whole brain irradiation must be stable without symptoms for 4 weeks after completion of treatment, with image documentation required, and must be either off steroids or on a stable does of steroids for ? 4 weeks prior to enrollment.
Known active central nervous system metastases, brain metastases, or carcinomatous meningitis
Known untreated central nervous system metastases and/or carcinomatous meningitis
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Known active CNS metastases or carcinomatous meningitis.
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Known active central nervous system metastases and/or carcinomatous meningitis
Known central nervous system (CNS) metastases and/or carcinomatous meningitis (includes past history or current metastasis)
Active central nervous system (CNS) metastases and/or carcinomatous meningitis
Has known active CNS metastases and/or carcinomatous meningitis
Has a known active central nervous system metastasis and/or carcinomatous meningitis.
Known active central nervous system metastases and/or carcinomatous meningitis.
Active central nervous system metastases and/or carcinomatous meningitis
Has known untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
Has clinically active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Known uncontrolled central nervous system (CNS) metastases and/or carcinomatous meningitis or known malignancy that progressed or required active treatment within the last 2 years
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
EXCLUSION - PARTICIPANT: Participants with known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Documented active or untreated central nervous system (CNS) metastases and/or carcinomatous meningitis;
Has known active (=growing) central nervous system (CNS) metastases and/or carcinomatous meningitis; radiation or resected brain metastasis are acceptable if clinically stable
Has radiographically detectable central nervous system metastases and/or carcinomatous meningitis as assessed by local site investigator at the time of diagnosis
Known untreated central nervous system metastases and/or carcinomatous meningitis.
Poorly controlled or symptomatic central nervous system (CNS) metastases or carcinomatous meningitis
Has known active CNS metastases and/or carcinomatous meningitis.
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis and/or has known active central nervous system (CNS) leukemia involvement
Known central nervous system (CNS) metastases and/or carcinomatous meningitis
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Subjects with untreated central nervous system (CNS) metastases or carcinomatous meningitis are excluded
Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
Has radiographically detectable (even if asymptomatic and/or previously treated) central nervous system (CNS) metastases and/or carcinomatous meningitis as assessed by local site investigator and radiology review/CIV
Has radiographically detectable (even if asymptomatic and/or previously treated) central nervous system (CNS) metastases and/or carcinomatous meningitis as assessed by local site investigator and radiology review
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Has radiographically detectable (even if asymptomatic and/or previously treated) central nervous system (CNS) metastases and/or carcinomatous meningitis as assessed by principal investigator (PI) and radiology review
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Active central nervous system metastasis and/or carcinomatous meningitis causing symptoms
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
Patients with carcinomatous meningitis or active central nervous system (CNS) metastases
Known untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Symptomatic Central nervous system (CNS) metastases and/or carcinomatous meningitis
Subject has known active central nervous system metastases and/or carcinomatous meningitis.
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Has known active (growing) central nervous system (CNS) metastases and/or carcinomatous meningitis; prior radiation or resection is acceptable if clinically stable for at least 4 weeks
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Known active untreated CNS metastases and/or carcinomatous meningitis.
Active uncontrolled/symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease
Known active central nervous system metastases and/or carcinomatous meningitis
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Active CNS metastases or carcinomatous meningitis
Has known history of, or any evidence of, central nervous system (CNS) metastases and/or carcinomatous meningitis.
Has known active central nervous system metastases and/or carcinomatous meningitis.
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Known active central nervous system metastases and/or carcinomatous meningitis.
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Has known active CNS metastases and/or carcinomatous meningitis.
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Has known active CNS metastases and/or carcinomatous meningitis.
Active central nervous system metastases and/or carcinomatous meningitis
Carcinomatous meningitis and/or symptomatic central nervous system (CNS) metastases.
Carcinomatous meningitis and/or symptomatic CNS metastases
Active central nervous system (CNS) metastases and/or carcinomatous meningitis
Known active central nervous system metastases and/or carcinomatous meningitis.
Has radiographically detectable central nervous system (CNS) metastases and/or carcinomatous meningitis
Known central nervous system metastases and/or carcinomatous meningitis
Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Active central nervous system metastases and/or carcinomatous meningitis
Known central nervous system (CNS) metastases and/or carcinomatous meningitis
Clinically apparent central nervous system metastases or carcinomatous meningitis
Known central nervous system (CNS) metastases and/or carcinomatous meningitis
Known central nervous system metastases and/or carcinomatous meningitis.
Known active central nervous system metastases and/or carcinomatous meningitis.
Known central nervous system metastases and/or carcinomatous meningitis
Known central nervous system metastases and/or carcinomatous meningitis
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Known central nervous system (CNS) metastases and/or carcinomatous meningitis
Active central nervous system metastases and/or carcinomatous meningitis
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Known or suspected brain or central nervous system (CNS) metastases, or carcinomatous meningitis
Has known active central nervous system disease and/or carcinomatous meningitis
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Active central nervous system (CNS) metastases and/or carcinomatous meningitis
Known active CNS metastases and/or carcinomatous meningitis
Has clinically active central nervous system (CNS) metastases and/or carcinomatous meningitis
Patients with either clinically apparent central nervous system metastases or carcinomatous meningitis are ineligible
The patient has either clinically apparent central nervous system metastases or carcinomatous meningitis
Has known active central nervous system metastases and/or carcinomatous meningitis.
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Known central nervous system (CNS) metastases and/or carcinomatous meningitis.
Has known active CNS metastases and/or carcinomatous meningitis.
Known active central nervous system metastases and/or carcinomatous meningitis.
Active Central Nervous System (CNS) metastases or carcinomatous meningitis
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Has known active (= growing) central nervous system (CNS) metastases and/or carcinomatous meningitis; radiation or resected brain metastasis are acceptable if clinically stable
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Has known active CNS metastases and/or carcinomatous meningitis.
Active central nervous system (CNS) metastases.
Central nervous system (CNS) metastases .
Patients with known symptomatic central nervous system metastases requiring steroids.
EXCLUSION CRITERIA FOR SECOND-LINE THERAPY: Known or suspected brain or central nervous system metastases, irrespective of prior treatment
EXCLUSION CRITERIA FOR THIRD-LINE THERAPY: Known or suspected brain or central nervous system metastases, irrespective of prior treatment
Symptomatic central nervous system metastases
Active central nervous system metastases
Central nervous system metastases
Active central nervous system metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth (patients with history of central nervous system [CNS] metastases or spinal cord compression are eligible if they are clinically stable for at least 4 weeks before first dose of investigational product and do not require high-dose steroid treatment).
History of seizure disorders or unstable central nervous system metastases
Central nervous system (CNS) metastases (brain or leptomeningeal)
Known central nervous system metastases
Uncontrolled central nervous system (CNS) metastases (previously treated with radiation and off steroids is acceptable)
Central nervous system (CNS) metastases or seizure disorder
Patients with known central nervous system metastases, including lymphomatous meningitis
Central nervous system metastases, including lymphomatous meningitis
Known central nervous system or visceral metastases
Patients with active central nervous system (CNS) disease or history of brain metastases are excluded from study
Active central nervous system metastases and/or leptomeningeal disease
Symptomatic central nervous system metastases
Uncontrolled central nervous system metastases
Patients/subjects with suspected or known central nervous system metastases unless adequately treated
Presence of symptomatic or uncontrolled central nervous system or leptomeningeal metastases
History or evidence of central nervous system (CNS) metastases (patients with pretreated metastases are eligible under certain conditions)
Patient has known active central nervous system metastases.
Active central nervous system (CNS) metastases.
Central nervous system (CNS) metastases: patients with known central nervous system metastases are excluded unless treated surgically or with radiotherapy and stable with no recurrent lesions for at least 3 months from the start of protocol therapy
Must not have suspected or known central nervous system metastases unless adequately treated
Patients with active central nervous system (CNS) disease or history of brain metastases are excluded from study
Patients with active central nervous system (CNS) disease or history of brain metastases are excluded from study
Active uncontrolled central nervous system (CNS) metastases
Participant has known history or inflammatory bowel disease, pneumonitis, or known uncontrolled metastases to the central nervous system (CNS) (with certain exceptions).
Untreated central nervous system metastases; patients with a history of brain metastases must have had no central nervous system (CNS)-directed therapy within the past 60 days and radiological assessment within 30 days of study entry demonstrating a lack of progressive CNS disease
Any history of central nervous system (CNS) metastases that is not adequately treated with surgery or SABR > 14 days prior
Distant metastatic disease including central nervous system (CNS) or leptomeningeal metastases is not allowed
Patients with active central nervous system (CNS) disease or history of brain metastases are excluded from study
Patient has central nervous system (CNS) metastases or seizure disorder
Patients may have central nervous system (CNS) metastases which have been treated and are radiographically stable for at least 4 weeks
Evidence of central nervous system (CNS) metastases
Previous radiotherapy for central nervous system metastases
Known central nervous system (CNS) metastases requiring treatment, such as surgery, radiation or steroids
Known cerebral metastases, central nervous system (CNS) or epidural tumor
Central nervous system (CNS) metastases or seizure disorder
Known central nervous system (CNS) metastases
Known central nervous system metastasis. Patients with history of central nervous system metastases are eligible if they are clinically or radiographically stable for at least 3 months and not taking steroids or anticonvulsants.
Presence of untreated or symptomatic central nervous system metastases, or central nervous system metastases that currently require local therapy (such as radiotherapy or surgery), or require doses of corticosteroids within the prior 4 weeks
Active central nervous system tumor or metastases
Presence of central nervous system (CNS) metastases
Known central nervous system brain metastases
Symptomatic central nervous system metastases
Active or history of central nervous system (CNS) metastases
Presence of known, active central nervous system (CNS) metastases
Any history of central nervous system (CNS) metastases that is not adequately treated (surgery or radiation) > 14 days prior to registration
Central nervous system (CNS) metastases or seizure disorder
Central nervous system (CNS) metastases if not stable for at least 2-3 months based on imaging, clinical assessment, use of steroids, or seizure disorder
Known central nervous system metastases
Patients must not have known active central nervous system (CNS) metastases; patients with known central nervous system metastases are excluded unless treated surgically or with radiotherapy, and stable with no recurrent lesions for at least 6 months
Distant metastatic disease including central nervous system (CNS) or leptomeningeal metastases is not allowed
Uncontrolled central nervous system metastases
Uncontrolled central nervous system metastases; treated, non-progressing central nervous system (CNS) disease (documented by brain magnetic resonance imaging [MRI]) off corticosteroids for at least 1 month are eligible
Patients with active central nervous system (CNS) metastases
Known central nervous system (CNS) metastases with active symptoms, or requiring anticonvulsive medications, or steroids
No brain or central nervous system (CNS) metastases
Active Central nervous system (CNS) metastases
Patient must have no prior history or current clinically apparent central nervous system metastases
Known central nervous system metastases or central nervous system as the only source of disease
Patient must not have a history of or clinical evidence of central nervous system metastases or leptomeningeal carcinomatosis, except for individuals who have had previously-treated central nervous system (CNS) metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medications (with the exception of Keppra) for 1 month prior to first dose of PD 0332991
Presence of or known history of brain/central nervous system (CNS) tumor or metastases
Known central nervous system metastases or central nervous system as the only source of disease
At the time of Day 1 of the study, subjects with central nervous system (CNS) metastases must have been treated and must be asymptomatic
Uncontrolled central nervous system metastases
Has known active central nervous system metastases
Patients are ineligible if they have any history of central nervous system (CNS) metastases
Individuals with known central nervous system (CNS) metastases, unless metastases are treated and stable and the individual does not require systemic steroids
Known brain or central nervous system metastases or history of uncontrolled seizures.
Individuals with known or suspected central nervous system metastases or individuals requiring chronic daily treatment with oral corticosteroids
Subject has uncontrolled metastases to the central nervous system (CNS).
Symptomatic central nervous system metastases (excluding Glioblastoma multiforrme (GBM) and Primary Central Nervous System Lymphoma (PCNSL). Subjects with brain metastases that have been previously treated and are stable for 6 weeks are allowed.
Subjects with active central nervous system metastases
Known or suspected central nervous system metastases
Active central nervous system (CNS) metastases requiring treatment
Primary central nervous system (CNS) malignancy or active metastases within 5 years
Have confirmed presence of central nervous system metastases
Patients with known central nervous system metastases.
Active central nervous system (CNS) metastases
Patients with brain metastases must have at least one site of measurable disease outside of the central nervous system
Subjects with active central nervous system (CNS) metastases are excluded
Phase 1b: History or evidence of central nervous system (CNS) metastases
Central nervous system (CNS) metastases or seizure disorder
Central nervous system metastases
Patients with a history of symptomatic central nervous system metastases, unless treated and asymptomatic
Active central nervous system (CNS) metastases.
Presence of known central nervous system or brain metastases
Patients with central nervous system (CNS) tumors or known brain metastases
Prior or concurrent central nervous system (CNS) metastases
Presence of symptomatic or uncontrolled brain or central nervous system metastases
Central nervous system (CNS) metastases
Central nervous system (CNS) disease, including treated brain metastases
Central nervous system (CNS) metastases
Asymptomatic, central nervous system metastases are permitted
No known central nervous system (CNS) metastases
Known history of central nervous system (CNS) metastases
Previous radiotherapy for cerebral metastases, central nervous system (CNS) or epidural tumor
Patients with known central nervous system (CNS) metastases, unless metastases are treated and stable and the patients do not require systemic steroids
Patient must not have a history of or clinical evidence of central nervous system metastases or leptomeningeal carcinomatosis, except for individuals who have had previously-treated central nervous system (CNS) metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medications (with the exception of Keppra) for 1 month prior to first dose of pazopanib
Central nervous system metastases unless: (1) metastases have been treated and have remained controlled for at least two weeks following treatment, AND (2) patient has no residual neurological dysfunction off corticosteroids for at least one week; a CT or MRI to evaluate for central nervous system (CNS) disease is required for symptomatic patients only
Known central nervous system (CNS) metastases
Known or suspected brain or other central nervous system (CNS) metastases
Active central nervous system (CNS) metastases
History or clinical evidence of central nervous system metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated central nervous system (CNS) metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 2 months prior to first dose of study drug
Patients with central nervous system (CNS) metastases are eligible (as long as projected survival is > 6 months)
Active or history of central nervous system metastases.
Active central nervous system metastases (subjects should be stable and off anticonvulsants and steroids)
Patient have uncontrolled brain metastases or central nervous system disease.
Active central nervous system metastases
History or known presence of central nervous system (CNS) metastases
Known central nervous system metastases
Known cerebral metastases, central nervous system (CNS) or epidural tumor
Central nervous system (CNS): no recent history (within 6 month) of cerebrovascular accident, transient ischemic attacks, central nervous system or brain metastases
Known active central nervous system (CNS) metastases.
Known or suspected brain or central nervous system metastases
Known central nervous system metastases
Symptomatic central nervous system metastases or lesions requiring treatment.
Subjects with active or symptomatic central nervous system metastases are excluded. Subjects with central nervous system metastases are eligible for the study if the metastases have been treated by surgery and/or radiation therapy, the subject is off corticosteroids for at least 2 weeks and the subject is neurologically stable
Central nervous system metastases
Patients are excluded if they have a history of central nervous system (CNS) metastases
Central nervous system (CNS) metastases or seizure disorder
Known central nervous system (CNS) or brain metastases.
Known central nervous system (CNS) disease, other than stable, treated brain metastases
Known presence of central nervous system metastases
Central nervous system metastases
Any history or signs of central nervous system metastases;
CNS (Central Nervous System) tumors as well as history of brain metastases
Known brain tumors or Central nervous system (CNS) metastases
Active central nervous system tumors or metastases
History or presence of known central nervous system metastases
Known central nervous system (CNS) disease except for treated brain metastases
Subjects with known central nervous system metastases.
History of Central nervous system (CNS) or brain metastases
Uncontrolled central nervous system metastases
No evidence of central nervous system (CNS) metastases
Unstable metastases to the central nervous system (CNS)
Have a known history of central nervous system disease (e.g., brain metastases or a seizure disorder)
Participants with central nervous system (CNS) (e.g., brain or leptomeningeal) metastases.
Known central nervous system metastases or central nervous system as the only source of disease
Known or suspected brain or other central nervous system metastases
Presence of symptomatic central nervous system metastases.
Uncontrolled Central Nervous System (CNS) metastases
Known metastases to the central nervous system
Central nervous system (CNS) metastases
Known meningeal involvement of multiple myeloma.
Exhibits clinical signs of meningeal involvement of MM
Meningeal carcinomatosis
Any active central nervous system or meningeal involvement
Exhibiting clinical signs of meningeal involvement of multiple myeloma
History or clinical signs of meningeal or active CNS involvement
Clinical signs of or documented leptomeningeal carcinomatosis. Features such as headache, nuchal rigidity, and photophobia may indicate meningeal involvement.
Documented history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, whole body magnetic resonance imaging (MRI) and lumbar cytology are required
Known active central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma
Subjects must not have known central nervous system involvement by disease (parenchymal, meningeal or cerebrospinal fluid)
Active meningeal or central nervous system disease
Participants who have known central nervous system, meningeal, or epidural disease including brain metastases.
Patients with CNS parenchymal or meningeal-based lesions that are present at study entry evaluation are NOT eligible
Presence of diffuse lepto or pachy meningeal carcinomatosis (focal/localized involvement from limited meningeal based metastases acceptable), greater than 1 cm mid-line shift, uncal herniation, or severe hemorrhage/hydrocephalous (small intra-lesional hemorrhage or anticipated surgical cavity is acceptable); patients with seizure at presentation who have been started on levetiracetam and have been stable for 48 hours prior to study registration are eligible at the discretion of treating physician
Central nervous system or meningeal involvement
Patients with active central nervous system (CNS) disease, defined as brain or meningeal metastases that are not in complete remission
Known meningeal involvement of MM.
Exhibiting clinical signs of or has a known history of meningeal or central nervous system involvement by multiple myeloma
Exhibiting clinical signs of meningeal involvement of multiple myeloma
New or progressive brain or meningeal or spinal metastases
Subject who has central nervous system (CNS) or meningeal involvement by lymphoma.
Participant is exhibiting clinical signs of meningeal involvement of multiple myeloma
Presence of meningeal carcinomatosis
Meningeal carcinomatosis
Patients with known central nervous system, meningeal, or epidural disease.
Clinical signs of meningeal involvement of multiple myeloma
Patient has active or history of central nervous system (CNS) disease or meningeal involvement
Subjects who have new or progressive brain or meningeal or spinal metastases.
Brain metastases, meningeal tumours or other metastases in the central nervous system
Uncontrolled central nervous system (CNS) metastases, meningeal carcinomatosis, malignant seizures, or a disease that either causes or threatens neurologic compromise (e.g., unstable vertebral metastases).
Presence of confirmed distant metastases, including central nervous system and vertebral or meningeal involvement
History or clinical evidence of central nervous system (CNS), meningeal, or epidural disease, including brain metastasis.
Active central nervous system or meningeal involvement by lymphoma; patients with a history of central nervous system (CNS) or meningeal involvement must be in a documented remission by cerebrospinal fluid (CSF) evaluation and contrast magnetic resonance imaging (MRI) for at least 3 months prior to study entry
Meningeal carcinomatosis.
Distant metastases, including CNS and vertebral or meningeal involvement
Patients with known central nervous system, meningeal, or epidural disease. Patients with stable brain metastases following definitive local treatment are eligible if steroid requirement is <10 mg/day of prednisone (or equivalent).
Subjects who have new or progressive brain or meningeal or spinal metastases
Known active meningeal infection
Uncontrolled meningeal leukemia
Meningeal carcinomatosis.
Known central nervous system, meningeal or epidural disease including brain metastases
Subjects who have new or progressive brain or meningeal or spinal metastases.
Diagnosed with meningeal carcinomatosis.
Patients with CNS involvement, including leptomeningeal carcinomatosis, which is either asymptomatic or previously-treated and controlled, are allowed
History of leptomeningeal carcinomatosis
Patients must be diagnosed with leptomeningeal carcinomatosis.
History of leptomeningeal carcinomatosis
History of leptomeningeal carcinomatosis.
Leptomeningeal carcinomatosis or other central nervous system (CNS) metastases
History of leptomeningeal carcinomatosis
History of leptomeningeal carcinomatosis
History of leptomeningeal carcinomatosis
Uncontrolled metastases to the central nervous system (CNS) or cytological/radiographic evidence of leptomeningeal carcinomatosis. Participants with brain metastases (other than leptomeningeal carcinomatosis) are eligible provided they do not require ongoing steroids and have shown clinical and radiographic stability for at least 28 days after definitive therapy. Primary glioblastoma is allowed.
History of leptomeningeal carcinomatosis
History of leptomeningeal carcinomatosis.
History of leptomeningeal carcinomatosis
History of leptomeningeal carcinomatosis
History of leptomeningeal carcinomatosis
History of leptomeningeal carcinomatosis
History of leptomeningeal carcinomatosis or brain metastasis.
History of leptomeningeal carcinomatosis
History of leptomeningeal carcinomatosis
Leptomeningeal carcinomatosis, diagnosed on cytology or appropriate imaging
History of leptomeningeal carcinomatosis
History of leptomeningeal carcinomatosis
History of leptomeningeal carcinomatosis
History of leptomeningeal carcinomatosis
History of leptomeningeal carcinomatosis
History of leptomeningeal carcinomatosis
Symptomatic and uncontrolled metastasis in the central nervous system or leptomeningeal or lymphangitic carcinomatosis
Leptomeningeal carcinomatosis
History of leptomeningeal carcinomatosis
Central nervous system (CNS) metastases including a history of leptomeningeal carcinomatosis
History of leptomeningeal carcinomatosis or uncontrolled seizures
History of leptomeningeal carcinomatosis or brain metastasis
History of leptomeningeal carcinomatosis
Cohort A only: Patients with leptomeningeal carcinomatosis are excluded. Other\n             central nervous system (CNS) metastases are only permitted if treated, asymptomatic,\n             and stable (not requiring steroid for at least 4 weeks prior to the start of study\n             treatment). Cohort B only: Patients with CNS metastases or leptomeningeal\n             carcinomatosis are excluded.
Leptomeningeal carcinomatosis as only site of CNS disease
Subjects with leptomeningeal carcinomatosis are not permitted
Subject has peritoneal carcinomatosis.
Lymphangitic carcinomatosis.
History of carcinomatosis meningitis
Diagnosis of leptomeningeal carcinomatosis
Brain metastases or history of leptomeningeal carcinomatosis
History of leptomeningeal carcinomatosis
History of leptomeningeal carcinomatosis
Unstable CNS metastases or leptomeningeal carcinomatosis not considered radiographically stable
Leptomeningeal carcinomatosis as the only site of CNS involvement
History of leptomeningeal carcinomatosis
History of leptomeningeal carcinomatosis
History of leptomeningeal carcinomatosis
History of leptomeningeal carcinomatosis
Patients must not have known central nervous system metastasis or a history of central nervous system (CNS) metastases; patients with leptomeningeal disease are not eligible
Subjects with inactive central nervous system (CNS) metastasis are eligible..
Active, untreated central nervous system (CNS) metastasis
History of central nervous system metastasis
Patient with active central nervous system (CNS) metastasis or with history of CNS metastasis
Have known central nervous system malignancy or metastasis.
Symptomatic central nervous system (CNS) malignancy or metastasis.
Patient with a tumor metastasis in the central nervous system
Have symptomatic central nervous system malignancy or metastasis.
Active central nervous system (CNS) or leptomeningeal metastasis (brain metastases)
Have symptomatic central nervous system (CNS) malignancy or metastasis.
Evidence of central nervous system (CNS) metastasis (negative imaging study, if clinically indicated, within 4 weeks of Screening Visit).
Symptomatic central nervous system metastasis (e.g., patients requiring increasing doses of steroids)
Have symptomatic central nervous system (CNS) malignancy (with the exception of medulloblastoma) or metastasis (screening not required).
Documented central nervous system metastases or liver metastasis
Central nervous system (CNS) metastasis.
Patients with history of prior central nervous system (CNS) metastasis must have been treated, must be asymptomatic, and must not have any of the following at the time of enrollment:
Uncontrolled central nervous system (CNS) metastasis; patients with CNS metastasis can be eligible if definitively treated with radiotherapy or surgery
Patients with active (untreated or relapsed) central nervous system (CNS) metastasis of the patient’s myeloma
Have known central nervous system malignancy or metastasis.
Central nervous system (CNS) metastasis, endometrial leiomyosarcoma, or endometrial stromal sarcoma.
Central nervous system (CNS) metastasis
About to undergo palliative radiation for a symptomatic central nervous system (CNS) metastasis
Central nervous system (CNS) metastasis
Documented central nervous system metastases or liver metastasis
Active (symptomatic) central nervous system (CNS) metastasis.
Presence of untreated and/or symptomatic central nervous system (CNS) metastasis
History of asymptomatic or symptomatic central nervous system (CNS) metastasis
Evidence of central nervous system (CNS) metastasis (negative imaging study, if clinically indicated, within 4 weeks of Screening Visit).
Known metastasis to the central nervous system
Known metastasis or symptoms of metastasis to the central nervous system
Patient with active central nervous system (CNS) metastasis or with history of CNS metastasis
History of central nervous system (CNS) metastasis.
Patients with active (untreated or relapsed) central nervous system (CNS) metastasis of the patient’s myeloma
Symptomatic central nervous system (CNS) metastasis.
Patients with known metastasis of malignant plasma cells to the central nervous system (if not suspected no specific testing is required)
Symptomatic brain metastasis or uncontrolled central nervous system (CNS) metastasis will not be permitted
Known history of central nervous system metastasis
Has active central nervous system (CNS) or leptomeningeal metastasis
Have symptomatic central nervous system metastasis. Screening of asymptomatic participants is not required for enrollment.
Central nervous system metastasis
Has a history of known central nervous system metastasis
Have known central nervous system metastasis or primary tumor (Part A). Previously-treated, CNS metastasis is permitted in Part B. CNS metastasis must be small, discrete metastasis; stable for at least 30 days without the need for concomitant prednisone for symptom management. No leptomeningeal disease is allowed. Is receiving therapeutic doses of corticosteroids (>20 mg prednisone daily or equivalent);
Central nervous system (CNS) metastasis.
Have the presence of unstable central nervous system (CNS) metastasis.
Have symptomatic central nervous system (CNS) malignancy or metastasis (screening not required).
Active or untreated central nervous system (CNS) metastasis
Have clinical evidence or a history of central nervous system (CNS) metastasis
Known untreated central nervous system (CNS) metastasis
Symptomatic Central Nervous System (CNS) metastasis
Parts A, B, D and E: Have central nervous system (CNS) metastasis with development of associated neurological changes 14 days prior to receiving study drug.
History of central nervous system metastasis.
Central nervous system (CNS) metastasis
Have clinical evidence or history of central nervous system metastasis.
Symptomatic central nervous system (CNS) malignancy or metastasis.
Have clinical evidence or history of central nervous system metastasis
Patients with active (untreated or relapsed) central nervous system (CNS) metastasis of the patient’s myeloma
History of central nervous system (CNS) metastasis that are untreated or not stable
Clinically unstable central nervous system (CNS) metastasis
Clinical evidence of central nervous system (CNS) metastasis.
Have malignancy or metastasis of the central nervous system
Presence or history of central nervous system metastasis (including brain)
For Dose Escalation (Part A): Have central nervous system (CNS) malignancy or metastasis
Known central nervous system metastasis
Patients with history of central nervous system (CNS) metastasis may not be enrolled on the study, unless control has been achieved with either radiation or surgical resection at least 3 months prior to enrollment on study
Known central nervous system metastasis that is unstable within the last 2 months
Have active central nervous system (CNS) metastasis
Central nervous system metastasis
Patients with known central nervous system metastasis are not eligible
Symptomatic central nervous system disease, malignancy, or metastasis
Subjects with known central nervous system (CNS) disease are not eligible, except for those subjects with treated brain metastasis.
Evidence of central nervous system metastasis
Known untreated central nervous system (CNS) metastasis
Known central nervous system (CNS) disease except for treated brain metastasis
Evidence of central nervous system (CNS) metastasis who have not received prior definitive therapy for their lesions.
Current uncontrolled central nervous system (CNS) metastasis or malignant brain tumors
Patients with Central Nervous System (CNS) metastasis which are: symptomatic or require treatment for symptom control and/or growing
Stage IV patients are considered provided they have a single non-central nervous system (CNS) metastasis (that is amenable to treatment with radiation therapy)
Known central nervous system metastasis
Symptomatic central nervous system malignancy or metastasis (screening not required).
Have symptomatic central nervous system (CNS) malignancy or metastasis
Patients with history of central nervous system (CNS) metastasis, unless control has been achieved with either radiation or surgical resection at least 3 months prior to enrollment on study
Active untreated central nervous system (CNS) metastasis
Known central nervous system metastasis
Known untreated central nervous system (CNS) metastasis; patients with CNS metastasis will be allowed on study once treated
Evidence of central nervous system metastasis and have not received prior definitive therapy for their lesions.
Known brain metastasis or primary central nervous system (CNS) malignancy
Patient must not have untreated or symptomatic central nervous system (CNS) metastasis
Known central nervous system (CNS) metastasis; once CNS metastasis have been treated these patients may participate if they are otherwise good trial candidates
Have symptomatic central nervous system (CNS) malignancy or metastasis.
Subjects with symptomatic brain metastasis or central nervous system (CNS) disease
Have central nervous system (CNS) metastasis with development of associated neurological changes 14 days prior to receiving study drug.
Part A: Patients with relapsed or refractory solid tumors, including patients with primary or metastatic CNS tumors
Brain Tumors
Tumors of all locations in the central nervous system, with appropriate histology, are eligible for study; however, patients with intrinsic brainstem tumors of the pons will be excluded from the study; patients with primary spinal cord lesions are allowed; patients with metastatic disease are also allowed
Histologically confirmed Rb1 positive primary recurrent, progressive, or refractory central nervous system tumors; patients with low grade gliomas are excluded
PROCUREMENT EXCLUSION CRITERIA: Patients diagnosed with primary central nervous system (CNS) tumors
Patients diagnosed with primary CNS tumors
Patients with primary CNS tumors are ineligible.
Ocular primary tumors.
Primary central nervous system (CNS) tumors or solid tumors with CNS metastases as the only site of active disease
PRE-REGISTRATION: Primary tumors of the central nervous system.
Subjects with resected primary tumors who have documented metastases are eligible
Patients with primary CNS tumors are not eligible
* Phase 1 (Part A1) - COMPLETE: Patients with relapsed or refractory solid tumors or anaplastic large cell lymphoma (excluding patients with primary or metastatic central nervous system [CNS] tumors or patients with primary cutaneous ALCL)
Clinically active primary central nervous system tumors or brain metastases with the exception of subjects with glioblastoma multiform that carry ROS1 rearrangement
Primary brain malignant tumors
Patients with primary tumors > 3 cm
Patients with primary brain tumors are excluded; patients with metastatic brain tumors may be enrolled
Patients with a histologically confirmed diagnosis of a primary CNS tumor that is recurrent, progressive or refractory to standard therapy; refractory disease will be defined as the presence of persistent abnormality on conventional magnetic resonance imaging (MRI) imaging that is further distinguished by histology (biopsy or sample of lesion) or advanced imaging, OR as determined by the treating physician and discussed with the primary investigator prior to enrollment; all tumors must have histological verification at either the time of diagnosis or recurrence except for patients with diffuse intrinsic brain stem tumors or optic pathway gliomas; patients with neurofibromatosis type-I (NF-1) associated CNS tumors are eligible if they meet all other eligibility criteria
Patients must have a histologically confirmed solid tumor malignancy at either original diagnosis or relapse for which no curative therapy exists, and which has either recurred or progressed after at least one prior systemic therapy; patients with primary brain tumors, or those with brain metastases at time of potential enrollment, are excluded; additionally, patients with gastrointestinal stomal tumors (GIST), alveolar soft part sarcoma, or dermatofibrosarcoma protuberans are excluded
Phase 1: All solid tumors (measurable or evaluable disease), including primary central nervous system (CNS) tumors; exclusion of hepatoblastoma and lymphomas
Known brain metastases or primary central nervous system tumors with seizures that are not well controlled with standard medical therapy
Patients with primary central nervous system tumors or brain metastases.
Patients with history or known presence of primary central nervous system (CNS) tumors, seizures not well-controlled with standard medical therapy, or history of stroke will also be excluded
Primary brain tumors or CNS metastases;
Evidence or history of central nervous system (CNS) disease, including primary brain tumors, seizures disorders, or any brain metastasis
Histologically confirmed solid tumors, including primary brain tumors; in subjects with brain stem or optic gliomas the requirement for histological confirmation may be waived
Patients with history or known presence of primary central nervous system (CNS) tumors, seizures not well-controlled with standard medical therapy, or history of stroke will also be excluded
Participants with primary brain tumors or disease metastatic to the brain.
Known primary central nervous system (CNS) tumors or brain metastases
Cohorts 2 & 3 only: Patients with secondary brain tumors must be greater than or equal to 4 weeks from radiotherapy. Patients with progressive secondary brain tumors will not be enrolled under this protocol following the completion of Cohort 3.
Symptomatic primary tumors or metastasis of brain and/or central nervous system that are uncontrolled with antiepileptics and requiring high doses of steroids
Histological or cytological documentation of non-hematologic, malignant solid tumor, excluding primary brain or spinal tumors, or history of central nervous system metastases
Patients with brain tumors
Primary brain tumors
Patients with brain metastases from primary germ cell tumors, small cell carcinoma, unknown primary, or lymphoma
Diagnosis of primary brain tumors
Symptomatic primary tumors or metastasis of brain and/or central nervous system, uncontrolled with antiepileptic and requiring high doses of steroids.
Patients presenting with brain tumors will be eligible for this study
Patients with primary brain tumors or primary tumors with central nervous system metastases as only location of disease. Controlled brain metastases are permitted
Patients with primary CNS tumors and leptomeningeal disease are ineligible.
Leptomeningeal disease or uncontrolled brain metastasis\r\n* NOTE: Metastases treated by surgery and/or radiotherapy such that patient is neurologically stable and off steroids >= 12 weeks prior to preregistration are eligible
Central nervous system (CNS) metastases may be permitted but must be treated and neurologically stable
Patients who have known brain metastasis; patients whose central nervous system (CNS) metastases have been treated by surgery or radiotherapy, who are no longer on corticosteroids, and who are neurologically stable are eligible
Patients with known brain metastases will only be eligible after their tumors have been treated with definitive resection and/or radiotherapy and they are neurologically stable for at least 1 month off steroids.
If they have untreated central nervous system (CNS) metastases; patients whose CNS metastases have been treated by surgery or radiotherapy, who are no longer on corticosteroids, and who are neurologically stable may be enrolled in the dose escalation portion of the trial
The subject is neurologically stable for at least 2 weeks prior to Screening.
Presence of brain metastases (unless they have been adequately treated with radiotherapy or surgery and stable for at least 30 days prior to enrollment provided patient is neurologically asymptomatic and without corticosteroid treatment for at least 7 days prior to enrollment)
Patients with untreated central nervous system (CNS) metastatic disease (including spinal cord and leptomeningeal disease) are excluded\r\n* Note: Subjects with previously treated CNS metastases that are radiographically and neurologically stable for at least 6 weeks and do not require corticosteroids (of any dose) for symptomatic management are permitted to enroll
Untreated central nervous system metastatic disease, leptomeningeal disease, or cord compression; subjects previously treated central nervous system metastases that are radiographically and neurologically stable for at least 6 weeks and do not require corticosteroids (of any dose) for symptomatic management for at least 14 days prior to first dose of MEDI4736 and tremelimumab are permitted to enroll
Known active central nervous system (CNS) disease - If patient has history of brain metastases, the brain lesions must have been treated with radiation and/or surgery- patients should be neurologically stable and on a stable or tapering dose of corticosteroids
Patients must not have untreated central nervous system (CNS) metastases; patients whose CNS metastases have been treated by surgery or radiotherapy, who are no longer on corticosteroids, and who are neurologically stable may be enrolled
Symptomatic or history of untreated brain or leptomeningeal metastases; treated patients should be neurologically stable for 4 weeks after completion of appropriate therapy; patients should be off steroids at least 3 days prior to start of therapy on clinical trial
Known malignant central nervous system (CNS) disease other than neurologically stable, treated brain metastases – defined as metastasis having no evidence of progression or hemorrhage for at least 2 weeks after treatment; must be off any systemic corticosteroids for the treatment of brain metastases for at least 14 days prior to enrolment
If they have untreated central nervous system (CNS) metastasis; patients whose CNS metastases have been treated by surgery or radiotherapy, who are no longer on corticosteroids, and who are neurologically stable may be enrolled in the dose escalation portion of the trial
Known central nervous system (CNS) disease other than neurologically stable, treated brain metastases - defined as metastasis having no evidence of progression or hemorrhage for at least 2 weeks after treatment (including brain radiotherapy). Must be off any systemic corticosteroids for the treatment of brain metastases for at least 14 days prior to enrollment.
Patients must be neurologically stable and with stable dose steroids and anticonvulsants for at least 1 week prior to obtaining the baseline MRI of the brain, and/or at least 1 week prior to beginning study treatment
Patients with treated brain metastasis as long as neurologically stable and not on steroids for at least 12 weeks
No untreated central nervous system metastases, or if treated must be neurologically stable for at least 2 weeks prior to enrollment
Patients with a history of CNS metastases must have received therapy (surgery, radiotherapy, gamma knife) and be neurologically stable, asymptomatic, and not receiving corticosteroids for the purposes of maintaining neurologic integrity. Patients with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired. For patients with parenchymal CNS metastasis (or a history of CNS metastasis), baseline and subsequent radiological imaging must include evaluation of the brain (MRI preferred or CT with contrast)
CNS disease other than neurologically stable, treated brain metastases.
Untreated brain metastases. Participants must have completed treatment for brain metastasis, and be neurologically stable off steroids, for at least 28 days prior to first dose of study drug
Uncontrolled central nervous system (CNS) metastases\r\n* NOTE: metastases have been treated by surgery and/or radiotherapy and patients have been neurologically stable and off of steroids > 12 weeks are eligible
Subjects must be neurologically stable for at least 14 days prior to first dose of study drug;
Central nervous system (CNS) metastases may be permitted but must be treated and neurologically stable
Have symptomatic CNS metastases that are neurologically unstable or require an increasing dose of corticosteroids.
Patients with known brain metastases will only be eligible after their tumors have been treated with definitive resection and/or radiotherapy and they are neurologically stable for at least 1 month off steroids.
Subjects with brain metastases are eligible providing they are neurologically stable (if systemic steroids are required, subjects should be stable on the lowest clinically effective dose, as steroids as they may interfere with the activity of ipilimumab if administered at the time of the first ipilimumab dose)
Is neurologically stable without the need for steroids for ?7 days before first dose of study treatment.
Patients with brain metastases are eligible if asymptomatic and neurologically stable for at least 4 weeks and are not taking any medications contraindicated
Brain metastasis unless treated and neurologically stable
Neurologically stable
Patient with symptomatic brain metastases, ie, not neurologically stable or requiring treatment with corticosteroids, or central nervous system (CNS) leukemia.
A history of CNS involvement except as follows: Subjects with previously treated CNS metastases that are adequately treated with whole brain radiotherapy, that are neurologically stable, and do not require corticosteroids for symptomatic management for at least 14 days prior to first dose of study drug. There must be no clear evidence of radiographically active disease for at least 90 days prior to enrollment.
Patients with central nervous system (CNS) metastases will be allowed on this study. Patients may have received surgical and/or radiation treatment. The metastases must be neurologically stable, on or off corticosteroids. Patients can have low level, asymptomatic brain lesions that do not require surgical/radiation intervention acutely. Patients with symptomatic lesions with impending neurologic compromise should be appropriately treated with high dose steroids/radiation and may be re-evaluated for this study when neurologically stable.
Known CNS metastases or leptomeningeal disease unless appropriately treated and neurologically stable for at least 4 weeks
Known brain or spinal cord metastases unless adequately treated (surgery or radiotherapy) with no evidence of progression and neurologically stable off anticonvulsants and steroids.
If patient has history of brain metastases, brain lesions should have been treated with surgery and/or radiation and be stable on repeat imaging and patients should be neurologically stable on a stable or tapering dose of corticosteroids
Untreated brain metastases. Subjects must have completed treatment for brain metastasis, and be neurologically stable off steroids, for at least 28 days prior to first dose of study drug
Known central nervous system (CNS) disease other than neurologically stable, treated brain metastases -- defined as metastasis having no evidence of progression or hemorrhage after treatment for at least 2 weeks
Presence of gliomas and brain metastases only if neurologically stable and treated without ongoing requirement for corticosteroids for at least 2 weeks.
Known central nervous system (CNS) metastases and/or carcinomatous meningitis; patients with radiated or resected lesions are permitted, provided the lesions are fully treated and inactive, patients are asymptomatic, and no steroids have been administered for at least 30 days prior to the start of study drug
Patients with active central nervous system (CNS) malignancy; asymptomatic small lesions are not considered active; treated lesions may be considered inactive if they are stable for at least 3 months
Patient with known central nervous system (CNS) metastasis (radiated or resected lesions are permitted, provided the lesions are fully treated and inactive, patient is asymptomatic, and no steroids have been administered for at least 30 days)
Known untreated central nervous system (CNS) metastases; Note: patients with radiated or resected lesions are permitted, provided the lesions are fully treated and inactive, patients are asymptomatic, and no steroids have been administered for this purpose =< 30 days prior to randomization
Patients with active central nervous system (CNS) malignancy; asymptomatic small lesions are not considered active; treated lesions may be considered inactive if they are stable for at least 3 months
Patients with active central nervous system (CNS) malignancy\r\n* Asymptomatic small lesions are not considered active\r\n* Treated lesions may be considered inactive if they are stable for at least 3 months
Patients with active central nervous system (CNS) malignancy; asymptomatic small lesions are not considered active; treated lesions may be considered inactive if they are stable for at least 3 months; patients with malignant cells in their cerebrospinal fluid (CSF) without CNS symptoms may be included
Patients with active central nervous system (CNS) malignancy; asymptomatic small lesions are not considered active; treated lesions may be considered inactive if they are stable for at least 3 months
Patients with active central nervous system (CNS) malignancy; asymptomatic small lesions are not considered active; treated lesions may be considered inactive if they are stable for at least 3 months; patients with malignant cells in their cerebrospinal fluid (CSF) without CNS symptoms may be included
Except for patients with GBM/ AnaA in the Expansion Phase, patients with active CNS malignancy are excluded. Asymptomatic small lesions are not considered active. Treated lesions may be considered inactive if they are stable for at least 3 months.
Patients with active CNS malignancy. Asymptomatic small lesions are not considered active. Treated lesions may be considered inactive if they are stable for at least 3 months. Patient with malignant cells in their cerebrospinal fluid (CSF) without CNS symptom may be included.