Participants must have progressive CNS lesions, as defined by one of the following:\r\n* Patients may have multiple progressive CNS lesions, some of which have been treated by stereotactic radiosurgery (SRS) or surgery; patients are eligible if they have one or more untreated (by surgery or SRS) progressive lesions that is measurable\r\n* Patients have measurable residual or progressive lesions after surgery\r\n* Patients who have had prior whole-brain radiotherapy (WBRT) and/or SRS are eligible but there needs to be unequivocal evidence of progression of at least one lesion treated by radiation (e.g. tissue diagnosis); biopsy can be considered for definitive diagnosis\r\n* Patients who have previously been treated with systemic therapy for CNS metastases are eligible
COHORT B: Progressive brain metastases after prior local CNS-directed therapy such as radiation or surgery as defined by:\r\n* Untreated measurable lesions in patients that have received surgery and/or SRS to one or more other lesions\r\n* Residual or progressive lesions after surgery if asymptomatic\r\n* Patients who have had prior whole-brain radiotherapy (WBRT) and/or SRS and then whose lesions have progressed are eligible; lesions treated with SRS may be eligible if there is unequivocal evidence of progression
New or progressive CNS lesions, as assessed by the patient’s treating physician\r\n* It is anticipated that some patients may have multiple progressive CNS lesions, one or several of which are treated with stereotactic radiosurgery (SRS) or surgery with residual untreated lesions remaining; such patients are eligible for enrollment on this study providing that at least one lesion is measurable (>= 10 mm) per RECIST 1.1; the location of the measurable lesion should be documented in the patient chart and case report form\r\n* Patients who have had prior cranial surgery are eligible provided that there is evidence of measurable residual or progressive lesions, and at least 3 months have passed since surgery; if a patient has surgical resection followed by whole brain radiation therapy (WBRT), then there must be evidence of progressive CNS disease after the completion of WBRT\r\n* Patients who had had prior WBRT and/or SRS and then whose lesions have progressed thereafter are also eligible; in this case, lesions that have been treated with SRS may be considered as target lesions if there is unequivocal evidence, in the opinion of the treating physician, of progression\r\n* Patient who have not previously been treated with cranial radiation (e.g. WBRT or SRS) are eligible to enter the study, but such patients must be asymptomatic or minimally symptomatic from their CNS metastases and not requiring corticosteroids
Patients unable to have SRS/SBRT through insurance coverage or ability to pay for SRS/SBRT
Patients unable to have SRS/SBRT through insurance coverage or ability to pay for SRS/SBRT
Participants must have a diagnosis of brain metastases for which SRS is indicated, as determined by a radiation oncologist
Participants must not have more than 5 new or progressive lesions in the brain requiring SRS treatment (greater than 5 total brain lesions are allowed as long as no more than 5 lesions require SRS treatment)
Prior local therapy:\r\n* Prior surgery, whole brain radiation or SRS is allowed as long as the most recent brain progression is amenable to SRS treatment
Unequivocal evidence of new and/or progressive brain metastases, and at least one of the following scenarios:\r\n* Treated with stereotactic radiosurgery (SRS) or surgery with residual un-treated lesions remaining; such participants are eligible for immediate enrollment on this study providing that at least one untreated lesion is measurable\r\n* Participants who have had prior whole- brain radiation therapy and/or SRS and then whose lesions have subsequently progressed are also eligible; in this case, lesions which have been treated with SRS may be considered as target lesions if there is unequivocal evidence, in the opinion of the treating physician, of progression following SRS \r\n* Participants who have not previously been treated with cranial radiation (e.g., WBRT or SRS) are eligible to enter the study, but such participants must be asymptomatic from their CNS metastases and not requiring corticosteroids for symptom control\r\n* Both participants who present with systemic stable/absent or progressive disease are eligible to this trial, as long as they fulfill one of the above criteria
Concurrent brain directed therapy (beyond SRS and NovoTTF-100M as per protocol)
No prior stereotactic radiosurgery (SRS) to the lesions which will be treated on protocol.
Patients who have had less than or equal to 5 metastases treated with SRS are eligible.
Patients receiving prior stereotactic radiosurgery (SRS) for brain metastases are eligible
Phase I Inclusion Criterion Only: Patients must have brain metastases, treated within 6 weeks of study entry with stereotactic radiosurgery (SRS) resection or whole brain radiation therapy (WBRT); a minimum interval of 3 weeks between completion of brain SRS and/or resection and 6 weeks for WBRT and the start of treatment  in this trial will be observed to allow proper healing; the presence of concomitant extracranial metastatic disease is allowed for enrollment
Phase II Inclusion Criterion Only: Patients must have 1-3 brain metastases, each < 3 cm by contrast MRI, treated within 6 weeks of study entry with SRS and/or resection; a minimum interval of 3 weeks between completion of brain SRS and/or resection and the start of treatment in this trial will be observed to allow proper healing; patients with 4 or 5 brain metastases will be evaluated case by case and may be eligible pending on the total field radiated; the presence of concomitant extracranial metastatic disease is allowed for enrollment
Symptomatic brain metastases requiring immediate local interventions such as craniotomy or stereotactic radiosurgery (SRS)
Previous cranial SRS/whole brain radiation therapy (WBRT) is allowed if > 3 months prior to single isocenter multi-target (SIMT)
All patients with 1-4 metastatic brain lesions who are considered eligible for single-fraction, frame-based SRS, who are unable or unwilling to undergo frame-based SRS
Prior cranial radiotherapy within 90 days of months of trial enrollment or prior SRS at any time to any lesion to be treated on protocol
Chemotherapy (including oral agents and targeted agents) or immunotherapy given within 14 days of SRS; hormonal therapy is permitted; for Her2+ breast cancer patients, anti-Her2 therapy cannot be given within 14 days of SRS; patients who are scheduled to receive trastuzumab emtansine after SRS cannot be enrolled
At least one brain lesion size >= 0.3 cm in the longest axis amenable to radiation therapy (either via SRS or WBRT)
Previous treatment with surgery, radiation, chemotherapy, immunotherapy or any targeted agents are allowed provided that:\r\n* Systemic therapy was administered >= 7 days before SRS\r\n* Radiation was not to the brain\r\n* Surgery to the brain was >= 7 days prior to SRS and there remains at least one additional brain metastasis that can be targeted with SRS
Patients had craniotomy and surgery to the brain within 7 days from the date of SRS
Patients must not be pregnant at the time of SRS treatment
Patients with controlled brain metastases are allowed on protocol if they had solitary brain metastases that was surgically resected without recurrence or treated with stereotactic radiosurgery (SRS) without progression x 4 weeks
Prior brain surgery is allowed, although a lesion situated in the operative bed would not be selected to receive an experimental dose of SRS treatment; SRS should be delivered 4-6 weeks post-surgery if the patient had a craniotomy for resection of a lesion; enrollment of a patient with the goal of performing SRS outside of the 4-6 post-craniotomy window is at the principal investigator (PI)’s discretion
For subjects currently on active systemic cancer therapy, the treating medical oncologist should be consulted to ensure proper washout (if appropriate) periods prior to SRS
Systemic chemotherapy delivered or planned to be delivered within (+/-) 5 days of SRS re-irradiation
Magnetic resonance imaging (MRI) evidence of 1-4 brain metastases, with at least one lesion > 20 mm and =< 50 mm in maximal diameter and determined to be appropriate for SRS and gross total resection; all other brain metastases are appropriate for SRS
Patient can have prior SRS to lesions other than the one planned for neoadjuvant SRS and resection
Subjects will be recruited from patients who are potential candidates for SRS treatment at Dartmouth Hitchcock Medical Center (DHMC) for brain metastases
Any patient undergoing SRS for brain metastases
Patients may have had prior therapy including:\r\n* Whole brain radiation therapy (WBRT) > 3 months ago\r\n* SRS to other brain metastases
Patients receiving SRS to resection bed
Patients will be excluded if they have had prior whole brain radiotherapy (WBRT) or prophylactic cranial irradiation (PCI); prior SRS or gamma knife radiosurgery to 1-3 metastases with minimum of (6) weeks to the most recent scan are allowed on protocol
Patients must not have received prior whole brain radiation therapy; previous SRS/SRT done at least 3 weeks from the planned start of IPdR therapy is acceptable; SRS/SRT/fractionated boosts or neurosurgery can be performed once the dose limiting toxicity (DLT) assessment has been completed, if felt clinically necessary
Have completed local therapy (surgical resection, WBRT, or SRS) ?14 days prior to initiating abemaciclib and recovered from all acute effects.
Require immediate local therapy, including but not limited to WBRT, SRS, or surgical resection, for treatment of brain metastases.
Patients may have brain lesions which measure =< 1cm each; lesions that are > 1 cm that have been treated with stereotactic radiosurgery (SRS) and in the opinion of the PI or his designee no longer represents active disease will also be allowed (Turnstile II - Chemotherapy/Cell Infusion- Inclusion Criteria)
Prior stereotactic radiosurgery (SRS) to adjacent lesion such that planning target volume would have received more than 12 Gy
Brain metastases from breast cancer with or without prior treatment; whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS) or surgical resection permitted through progression; progression must be documented in an at least one lesion untreated by SRS or in any site after surgery or WBRT
Patients must be candidates for SRS and planning to undergo SRS
Patients with 1-3 brain metastases, each < 3 cm by contrast MRI, with stable systemic disease and ECOG score of 0-2, who would otherwise be eligible for SRS/stereotactic radiation therapy (SRT) alone should not be enrolled into this study unless WBRT is recommended due to any medical reasons or logistic limitations as determined by the treating physician; patients who develop recurrence post-SRS/SRT or surgery alone and are recommended WBRT will be eligible for the protocol
Patients must not have received prior WBRT (previous SRS/SRT done at least 4 weeks from the planned start of WBRT is acceptable); patients planned upfront to undergo SRS/SRT/fractionated boosts or neurosurgery after WBRT are not eligible; however, these treatments/procedures can be performed once the dose limiting toxicity (DLT) assessment has been completed, if felt clinically necessary
Received chemotherapy or radiation within 14 days of first dose of study drug, except stereotactic radiosurgery (SRS) or stereotactic body radiation therapy (SBRT).
Diagnosis of CNS metastases for whom SRS or WBRT is indicated, as determined by radiation oncologist assessment
Surgical resection or stereotactic radiosurgery (SRS) to other recurrent lesions in the same patient are acceptable, provided one recurrent lesion remains untreated
Received cytotoxic chemotherapy, investigational agents, or radiation within 14 days, except SRS or stereotactic body radiosurgery.
New or progressive CNS lesions, as assessed by the patient’s treating physician, with at least one of the following clinical scenarios:\r\n* It is anticipated that some participants may have multiple progressive CNS lesions, one or several of which are treated with stereotactic radiosurgery (SRS) or surgery with residual un-treated lesions remaining; such participants are eligible for immediate enrollment on this study providing that at least one untreated lesion is measurable; the location of the measurable lesion should be documented in the patient chart and case report form\r\n* Participants who have had prior cranial surgery are eligible, provided that there is evidence of measurable residual or progressive lesions; if a patient has surgical resection followed by whole brain radiation therapy (WBRT) and/or SRS, then there must be evidence of progressive CNS disease after the completion of WBRT and/or SRS\r\n* Participants who have had prior WBRT and/or SRS and then whose lesions have progressed thereafter are also eligible; in this case, lesions which have been treated with SRS may be considered as target lesions if there is unequivocal evidence, in the opinion of the treating physician, of progression following SRS\r\n* Participants who have not previously been treated with cranial radiation (e.g. WBRT or SRS) are eligible to enter the study, but such participants must be asymptomatic from their CNS metastases and not requiring corticosteroids
Treating physician must deem that SRS is appropriate treatment for the metastatic spinal lesion(s)
Each SRS target must be the equivalent of =< 3 vertebral levels
For cohorts 1 and 3a/3b, patients must have new or progressive measurable central CNS lesions, as assessed by the patient's treating physician; this includes patients who have progressed after at least one line of standard treatment for CNS disease (whole brain radiotherapy [WBRT], stereotactic radiosurgery [SRS], or surgical resection as below)
It is anticipated that some patients may have multiple progressive CNS lesions, one or several of which are treated with SRS or surgery with residual untreated lesions remaining; such patients are eligible for enrollment on this study providing that at least one residual (i.e. non-SRS-treated or non-resected) lesion is measurable (>= 10 mm); the location of the measurable lesion should be documented in the patient chart and case report form
Patients who have had prior WBRT and/or SRS and then whose prior treated lesions have progressed thereafter are also eligible; in this case, lesions which have been treated with SRS may be considered as target lesions if there is unequivocal evidence, in the opinion of the treating physician, of progression
For patients who undergo surgery, postoperative whole brain radiation therapy will not be allowed while patients are on study; patients will require discontinuation of neratinib if WBRT will be administered; however, if the treating provider feels that targeted radiosurgery (SRS, gamma knife, etc) would be of benefit postoperatively, patients may proceed with this and then begin neratinib AFTER radiation completes
Patients with measurable brain metastasis who have not been or will not be treated with stereotactic radiosurgery (SRS) or surgical resection (Note: these treatment options are only permitted at relapse)
Planned cytotoxic chemotherapy during the SRS or WBRT
Any stereotactic radiosurgery (SRS) was completed at least 1 week prior to the first dose of study drug.
Patients can have previous brain metastasis that was treated with stereotactic radiosurgery (SRS) if the previously treated lesion is at least 1 cm from the target lesion(s) for this study; the location of the previous SRS treatment location is determined by the SRS MRI
Prior Central Nervous System (CNS)-directed local therapies, including surgical resection, whole brain radiation (WBRT), Stereotactic radiosurgery (SRS), or gamma knife (GK)
Planned WBRT based on number (>= 3 lesions) and/or size (>= 1 cm) of brain metastases (BMs); patients who require additional clinically indicated stereotactic radiosurgery (SRS) in addition to WBRT will also be eligible
Patients with prior SRS will also be eligible, provided that there are new, non-irradiated measurable brain lesions
Up to 2 additional intact brain metastases to be treated with stereotactic radiosurgery (SRS) alone
Previous brain radiotherapy (SRS or whole brain radiation therapy [WBRT])
Stereotactic radiosurgery (SRS):\r\n* Patients must have confirmation of true progressive disease rather than radiation necrosis based upon either PET or Thallium SPECT, MR spectroscopy and MR perfusion or surgical documentation of disease\r\n* At least 12 weeks between completion of SRS and initiation of bendamustine
Eligibility for treatment with SRS confirmed by a radiation oncologist
Not eligible for Stereotactic Radiosurgery (SRS) treatment of brain tumor.
Patients who require additional clinically indicated stereotactic radiosurgery (SRS) in addition to WBRT will also be eligible
Evolving brain lesions post SRS requiring neurosurgical resection (whether for symptomatic control or to establish pathology)
Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible; lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible; patients with surgically resected brain metastases are eligible
Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible; lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible; patients with surgically resected brain metastases are eligible
Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible; lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible; patients with surgically resected brain metastases are eligible
Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible.
Patients with 3 or fewer brain metastases that are less than 1 centimeter (cm) in diameter and asymptomatic are eligible; lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month after treatment for the patient to be eligible; patients with surgically resected brain metastases are eligible
For cohorts 1-3, patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible; lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible; patients with surgically resected brain metastases are eligible
Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible; lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month after treatment for the patient to be eligible; patients with surgically resected brain metastases are eligible
Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible; lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible; patients with surgically resected brain metastases are eligible
Patients with three or fewer brain metastases that have been treated with surgery or stereotactic radiosurgery are eligible; lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month before protocol treatment; patients with surgically resected brain metastases are eligible
Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible; lesions > 1 cm that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible; patients with surgically resected brain metastases are eligible
Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible; lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible; patients with surgically resected brain metastases are eligible
Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible; lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible; patients with surgically resected brain metastases are eligible
Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible; lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible; patients with surgically resected brain metastases are eligible
Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible
Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible; lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible; patients with surgically resected brain metastases are eligible
Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible; lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible; patients with surgically resected brain metastases are eligible
Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible; lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible
Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible; lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible; patients with surgically resectable brain metastases are eligible
Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible; lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible; patients with surgically resected brain metastases are eligible
Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible; lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible
Patients with 3 or less brain metastases that are less than 1 cm in diameter and asymptomatic are eligible; lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible; patients with surgically resected brain metastases are eligible
Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible; lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible; patients with surgically resected brain metastases are eligible
Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible; lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible
Patients with brain metastases or primary brain tumors must have completed treatment, surgery or radiation therapy >= 4 weeks prior to start of treatment
No radiation therapy (other than to the brain) within 14 days of day 1 of protocol chemotherapy except radiation to brain metastases, which must be completed 7 days prior to start of chemotherapy
No large (>= 2 cm) hemorrhagic or symptomatic brain metastases until local treatment has been administered (radiation therapy or surgery); treatment may begin >= 7 days after completion of local treatment; patients with small (< 2 cm) and asymptomatic brain metastases are allowed and may be treated with radiation therapy and/or surgery concurrently with Arm A or cycles 1 and 2 of Arm B if deemed medically indicated; radiation therapy should not be given concurrently with high-dose carboplatin or etoposide
COHORT D: 1-4 brain metastases (where stereotactic radiosurgery would be indicated)
Will need immediate local surgery or radiation for their brain metastases
Partial brain radiotherapy (i.e. =< 40% of total brain volume) within the last 2 weeks
Whole brain radiotherapy within the last 6 months or partial brain radiotherapy exceeding > 40% of total brain volume within the last 6 months
Participants who have received prophylactic cranial radiation for prevention of brain metastases
Or have required any type of major treatment, e.g., whole brain radiation treatment, adjuvant chemotherapy, gamma knife, to control symptoms from brain metastases within 30 days of the first study treatment.
Patients with known brain metastases will be eligible as long as they have completed radiation to the brain, and have been off of corticosteroid therapy for at least 7 days
Patients who need whole brain radiation to control the brain metastases. Patients will not be eligible unless treated brain lesions are progressive or new brain lesions are observed since the post whole brain radiation therapy MRI.
Planning of any brain local treatment (including but not limited to surgery, stereotactic radiosurgery, whole brain radiation, intrathecal chemotherapy) following the administration of the first dose of study drug.
Prior radiation treatment to the brain
Previous whole brain radiation therapy
Planned adjuvant focal therapy including additional radiation therapy to the brain
Must have received prior radiation therapy for brain metastases or be ineligible for radiation therapy
Patients treated metastatic lesions to the brain may be enrolled after completing stereotactic radiosurgery (may enroll 14 days after treatment) or whole brain radiation (may enroll 14 days after treatment) and being weaned off corticosteroids (may enroll 14 days after weaning)
Patients with untreated brain metastasis; patients with metastatic lesions to the brain may be enrolled after completing stereotactic radiosurgery or whole brain radiation (may enroll 14 days after treatment and must be off corticosteroids for at least 14 days prior to the start of study treatment
Previously treated with surgery, whole-brain radiation, or stereotactic radiosurgery, and
History of radiation therapy to the brain for prior diagnosis of glioma
Determination by the treating radiation oncologist that the patient is a candidate for SRT (i.e., radiation therapy with a stereotactic setup)\r\n* Note: All brain metastases will receive SRT
Previous radiation to the brain, including WBRT or brain radiosurgery
At least 28 days from prior definitive treatment of their CNS disease by surgical resection, stereotactic body radiation therapy (SBRT) or whole brain radiation treatment (WBRT) at the time of registration
Have had prior radiation therapy to the brain or prior treatment for their brain tumor (except prior biopsy or subtotal resection)
Patients who have received radiation to brain and/or spine, including whole brain radiation, stereotactic radiosurgery, or stereotactic body radiation therapy (SBRT), are eligible, but must have completed radiation treatment at least 7 days prior to the start of treatment
Major surgery < 4 weeks or radiation therapy < 2 weeks of starting the study treatment; prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been irradiated\r\n* Radiotherapy is defined as whole brain radiation, external beam radiation therapy (EBRT), or stereotactic brain radiation (SBRT)
Prior radiation therapy to the brain besides radiosurgery
A history of previously treated brain metastases is allowed, provided that at least 7 days have lapsed between radiation and initiation of pembrolizumab; any brain metastasis >= 20 mm or causing symptoms must be treated with local therapy (i.e. radiation or surgical resection, as clinically appropriate) prior to study enrollment; any lesion present at the time of whole brain radiotherapy (WBRT) or included in the stereotactic radiotherapy field (or within 2 mm of the treated lesion) will NOT be considered evaluable unless it is new or documented to have progressed since treatment
Patients will have no more than 4 distinct lesions within the brain; at least 1 lesion has been recommended for surgical removal based on size, symptomology, or regional mass effect on the brain
History of prior radiation therapy to brain or skeleton is allowed, but should have occurred > 2 months from enrollment
A history of previously treated brain metastases is allowed, provided that at least 14 days have lapsed between radiation and initiation of MK-3475; any lesion present at the time of whole-brain radiotherapy (WBRT) or included in the stereotactic radiotherapy field (or within 2mm of the treated lesion) will NOT be considered evaluable unless it is new or documented to have progressed since treatment
Prior whole brain radiation therapy (WBRT)
At least 14 days passed since last brain surgery or radiation therapy.
Prior whole brain radiation therapy
Prior radiation to the brain
At least 14 days passed since last brain surgery, or intracranial radiation therapy/radiosurgery
Tumor location on both sides of the brain and/or involvement that would present the risk of injecting DNX-2401 into the ventricles of the brain
Brain metastases per MRI or CT at any time prior to registration; NOTE: patients that have had primary therapy for brain metastasis (i.e. surgical resection, whole brain radiation, or stereotactic radiotherapy [SRT] even if stable) are not eligible
Resection of brain metastases, otherwise untreated with radiation for those brain lesions (presenting for postoperative consolidative radiotherapy)
Brain metastases may be treated using gamma knife radiosurgery (GKR) or whole brain radiation therapy (WBRT) per the treating radiation oncologist; total radiation dose and number of fractions will be determined by the treating radiation oncologist based on anatomic and dosing constraints; magnetic resonance imaging (MRI) of the vertebral column is required for all patients with suspected epidural tumor extension
Patient may have received previous treatment for the brain tumor(s), including radiation (focal brain radiation, whole brain radiation or stereotactic radiosurgery), surgery or chemotherapy
Prior brain surgery or radiation is allowed as long as the metastatic lesion(s) to be targeted in this study has not previously been treated with radiation
Prior radiation therapy to the whole brain (prior stereotactic radiosurgery or fractionated stereotactic radiation therapy to focal areas is allowed)
Unable to reliably be immobilized for safe administration of whole brain radiation therapy
At least one measurable lesion in the brain (>= 10 mm on T1-weighted, gadolinium-enhanced magnetic resonance imaging [MRI]); (prior neurosurgical resection, whole brain radiation or stereotactic radiation therapy is allowed provided the patient has a measurable CNS progression [at least one new and/or progressive measurable brain metastasis]; measurable or non-measurable extracranial metastases allowed); if the potential participant has received brain radiation there needs to be at least one new and/or progressive measurable brain metastases after radiation is completed; do not consent patients if you are planning on administering brain radiation therapy
Prior radiation for bone or brain metastases is permitted if patient is now asymptomatic and has completed all radiation and steroid therapy (if applicable) for brain or bone metastases >= 2 weeks prior to study enrollment
Previous whole brain radiation therapy
Subjects with brain metastases as their first site of disease recurrence may be eligible if treated by definitive radiation (stereotactic radiosurgery or whole brain) with clinically controlled neurologic symptoms for a period of 21 days prior to study treatment
Progression of or new brain metastases after completion of whole-brain radiotherapy or stereotactic radiosurgery
Completion of whole-brain radiotherapy or stereotactic radiosurgery more than 60 days prior to enrollment
At least one measurable BM by RECIST 1.1 criteria (? 10mm in longest diameter). Target lesions must not have received stereotactic radiotherapy (SRS). If subject had prior whole brain radiotherapy (WBRT), progression in any measurable BM lesion must have occurred at least 3 months after the end of WBRT. Subjects with asymptomatic brain metastases may be enrolled without prior radiation therapy to the brain. Subjects with minimally symptomatic brain metastases may be enrolled without prior radiation therapy to the brain if they do not require immediate surgical or radiation therapy in the opinion of the treating investigator and in the opinion of a radiation therapy or neurosurgical consultant
Prior therapy for brain metastases is not required; patients may either have refused radiation therapy or have received prior radiation therapy; patients having received prior standard whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) must have completed treatment greater than 4 weeks prior to study initiation; patients are either inappropriate candidates for surgical resection or they may have refused surgical resection
Prior radiation therapy to the brain is allowed with the exception of whole brain irradiation
Patients with known brain metastases will be eligible as long as they have completed radiation to the brain and have been off of corticosteroid therapy for at least 2 weeks prior to study treatment
Patients will be excluded if they have had prior radiation to the brain
Patients will be excluded if they have had prior surgical resection of brain for other brain tumors
Concurrent radiation therapy is not allowed with the exception of brain metastases developing on study treatment
Patients receiving whole brain radiation within 14 days prior to the first dose of study drugs will be excluded; NOTE: patients receiving palliative radiation (other than whole brain) before or during treatment may still be eligible as long as there are evaluable lesions that are not being irradiated
No prior radiation therapy, surgery, or other local therapy for target brain lesions
Prior radiation therapy to the brain
Prior intracranial radiation therapy (whole brain radiation therapy, stereotactic radiosurgery, gamma knife, or equivalent) is allowed, but not required
Has completed treatment (eg, whole brain radiation treatment [WBRT], stereotactic radiosurgery, or equivalent) ?14 days prior to the first dose of study treatment,
Patients who have received prior radiation therapy to the brain for any reason
Subjects with asymptomatic brain metastases found on screening MRI may be entered into Phase 1b or into Group 2 of the Phase 2a without prior radiation therapy to the brain. Subjects with minimally symptomatic brain metastases found on screening MRI may be entered into Phase 1b or into Group 2 of the Phase 2a without prior radiation therapy to the brain if they do not require immediate surgical or radiation therapy
Deep brain stimulator
Prior radiation therapy to the brain
Concurrent or previous anti-cancer chemotherapy, immunotherapy or investigational agents < 3 weeks, or palliative radiation < 2 weeks prior to the first day of study treatment. Patients who receive gamma knife radiosurgery for brain metastases or whole brain radiation are eligible if gamma knife radiosurgery was performed > 2 weeks before treatment is started or whole brain radiation was performed > 4 weeks before treatment is started, and are clinically stable.
No history of prior whole brain radiation
Treatment with stereotactic radiosurgery or treatment with whole-brain radiation within treatment specific timeframe.
Histologically confirmed initial diagnosis of primary WHO Grade IV malignant glioma (glioblastoma), now recurrent; or Cohorts 2 and 3 only: progressive secondary brain tumor, has failed standard brain radiotherapy, and has brain tumor progression after at least one line of systemic therapy. Patients with progressive secondary brain tumors will not be enrolled under this protocol following the completion of Cohort 3.
Brain stem involvement allowed
No conditions that may compromise blood-brain barrier permeability (e.g., multiple sclerosis, recent brain trauma, Alzheimer’s disease, or uncontrolled seizures)\r\n* No symptomatic and untreated brain metastases; patients will be eligible for study if radiation therapy for brain metastases was completed at least 7 days prior to registration\r\n* Patients having received stereotactic radiation will be eligible if the radiation was completed at least 7 days prior to registration\r\n* Patients having undergone surgical resection of brain metastases will be eligible after they have healed and recovered from the surgical intervention sufficiently to start systemic treatment for NSCLC, as determined by a neurosurgeon\r\n* No known leptomeningeal carcinomatosis
BRAIN CANCER: Status post concurrent radiation therapy and daily temozolomide
SUBJECT: Must be at least 1 year post completion of radiation therapy to the brain or brain and spine.
Prior external beam radiation therapy to the brain or whole brain radiation therapy\r\n* Prior single-fraction or fractionated radiosurgery is permitted
Prior radiation therapy to the brain
Medical treatment plan includes whole-brain radiation therapy and/or stereotactic radiosurgery
Metastatic cancer to the brain for which palliative whole brain radiotherapy is recommended.
Whole-brain radiation ? 6 weeks
Brain metastases requiring focal or whole brain radiation will be excluded
Prior brain tumor treatment, including surgical resection, radiation therapy or chemotherapy for a primary brain neoplasm. Previous biopsy will not disqualify the patient from participation. Remote history (> 6 month) of non-CNS malignancy in remission, without evidence of current/ prior brain metastasis, will also not disqualify patient from participating.
Prior brain cancer
Prior whole brain radiation
History of radiation therapy to the brain
Completed fractionated radiation therapy (to 60 Gy for high grade gliomas) or stereotactic radiosurgery or hypofractionated radiation therapy (e.g. for brain metastases, anaplastic meningiomas), without or with concurrent chemotherapy
Any indication of a risk for an imminent brain herniation, as evaluated by the Principal Investigator, based on the findings on brain MRI.
Treatment with whole brain radiation therapy (WBRT) within 3 months prior to screening.
Patient must meet at least one of the four following criteria regarding brain tumor diagnosis:\r\n* Histological diagnosis of a brain tumor\r\n* Histological diagnosis of systemic cancer and brain MR imaging suggestive of metastatic disease to the brain\r\n* Pre-operative brain MR imaging suggestive of a brain tumor\r\n* Radiographic diagnosis of brain tumor in an inoperable location (e.g., brainstem)
Patient must be clinically eligible for and elect to be treated with GK alone without whole-brain radiation therapy (WBRT)
Patients must be scheduled to undergo standard brain cancer interventions:\r\n* Chemotherapy or targeted antiangiogenic therapy, in the case of primary brain tumor; or\r\n* Stereotaxic radiotherapy (SRS) or whole brain radiotherapy (WBRT), in the case of brain metastases
Patients with cancer that spread to the brain