Primary brain tumors or clinical evidence of active brain metastasis
Patients with symptomatic brain or bone metastasis are NOT eligible for participation; prior radiation and/or steroid therapy for brain or bone metastasis (mets) must be completed >= 2 weeks prior to study enrollment
Stable brain metastasis allowed (> 2 weeks, clinically stable post treatment with surgery +/- radiation or radiation alone and off steroids)
Untreated or uncontrolled brain metastasis.
Patients with symptomatic brain metastases; subjects with untreated brain metastasis =< 1 cm can be considered eligible if deemed asymptomatic by the investigator upon consultation with the medical monitor and do not require immediate radiation or steroids; subjects with brain metastasis that is treated and stable for 1 month may be considered eligible if they are asymptomatic and on stable dose of steroids or if they do not require steroids following successful local therapy
Subjects who have a history of brain metastasis are eligible for the study provided all the following criteria are met:\r\n* Must have completed their treatment for brain metastasis\r\n* Must be asymptomatic\r\n* Must not have evidence of disease progression for >= 3 months or hemorrhage after treatment\r\n* Must be off-treatment from dexamethasone for 4 weeks prior to study registration and\r\n* Must not have an ongoing requirement for dexamethasone or anti-epileptic drugs
Have brain metastasis without prior radiotherapy.
Primary brain tumor or active brain metastasis
Active or previous brain metastasis
Presence of untreated brain metastasis
At least one measurable lesion per RANO-BM (Response Assessment in Neuro-Oncology Brain Metastases) Criteria for brain metastasis
Patients who have a single, operable brain metastasis
No history of intracranial brain metastasis
INCLUSION CRITERIA FOR REGISTRATION (HER2 MUTATION IDENTIFIED BY WASH U GPS LABORATORY): Patients with known treated brain metastasis are eligible, but must have received radiation and be off steroids and stable (without evidence of disease progression by imaging or exam) for 3 months
INCLUSION CRITERIA FOR REGISTRATION (HER2 MUTATION IDENTIFIED AT AN OUTSIDE CLIA CERTIFIED LOCATION): Patients with known treated brain metastasis are eligible, but must have received radiation and be off steroids and stable (without evidence of disease progression by imaging or exam) for 3 months
Bulky intracranial metastatic disease with shift of midline structures or progressive brain metastasis such that ongoing therapy for these brain metastasis is required at the time of enrollment.
No active brain metastasis; previously surgically treated or irradiated lesions are allowed if not clinically active
At least one measurable lesion per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) Criteria for brain metastasis
A subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis at least 4 weeks prior to study registration, have been off of corticosteroids for >= 2 weeks, and are asymptomatic
The participant has active central nervous system (CNS) or leptomeningeal metastasis (brain metastasis) at the time of enrollment (Phase 1b) or randomization (Phase 2). Participants with a history of a CNS metastasis previously treated with curative intent (for example, stereotactic radiation or surgery) that have not progressed on follow-up imaging, have been asymptomatic for at least 60 days, and are not receiving systemic corticosteroids and or/anticonvulsants, are eligible. Participants with signs or symptoms of neurological compromise should have appropriate radiographic imaging performed before enrollment (Phase 1b) /randomization (Phase 2) to rule out brain metastasis.
Patients with known symptomatic brain metastasis; subjects with controlled brain metastasis (no radiographic progression at least 4 weeks following radiation and/or surgical treatment and no neurological signs or symptoms) will be allowed
Have active central nervous system (CNS) or leptomeningeal metastasis (brain metastasis) at the time of enrollment. Participants with a history of CNS metastasis (previously treated with curative intent [for example, stereotactic radiation or surgery]) that has not progressed on follow-up imaging, have been asymptomatic for at least 60 days, and are not receiving systemic corticosteroids and/or anticonvulsants are eligible. Participants with signs or symptoms of neurological compromise should have appropriate radiographic imaging performed before enrollment to rule out brain metastasis.
History of uncontrolled brain metastasis unless:
Primary brain tumors or known brain metastasis unless clinically stable and on stable or reducing doses of steroids.
Patient with brain metastasis must have had treatment of their brain metastasis completed at least 1 day prior to enrollment and be on stable dose of steroids or off steroids at the time of enrollment
Patients with PDA metastases deemed likely to limit the patient’s ability to participate in the study for the complete duration (ie. > 3 months), including but not limited to:\r\n* Presence of central nervous system (CNS) metastasis including brain metastasis or compromise resulting from extrinsic disease in the bone or dura\r\n* Presence of more than 5 liver metastases or one liver metastasis measuring more than 3 cm\r\n* Cancer antigen (CA)19-9 > 3000 U/mL\r\n* Oxygen requirement attributable to pleural effusion or other malignant process\r\n* Symptomatic ascites or radiographic evidence of more than trace ascites
Untreated brain metastasis(es) that may be considered active
Patients with active brain metastases should be excluded from this clinical trial; patients with prior history of brain metastasis who have undergone local therapy (i.e., metastasectomy and/or radiation) and show no evidence of local recurrence or progression over the past 6 months are eligible
Subjects with controlled brain metastasis (no radiographic progression at least 4 weeks following radiation and/or surgical treatment, off steroids for at least 4 weeks, and have no new or progressing neurological signs or symptoms) will be allowed
Active/untreated brain metastasis; whole brain radiation or gamma knife radiosurgery performed less than 4 weeks prior to first administration of study drug; previously treated brain metastasis allowed as long as not requiring steroids and stable on imaging at least 4 weeks after completing radiation therapy
Active/untreated brain metastasis: whole brain radiation or gamma knife radiosurgery performed less than 4 weeks prior to first administration of study drug; previously treated brain metastasis allowed as long as not requiring steroids and stable on imaging at least 4 weeks after completing radiation therapy
Brain metastasis allowed if previously treated, stable and off steroids for a minimum of 56 days
Patients with brain metastasis that have been treated with definitive surgery or radiation and have been clinically stable for 3 months are eligible
Patients with untreated brain metastasis are excluded; patients with a prior history of brain metastasis are eligible if they have received prior brain radiation, have improved or stable intracranial disease for at least 3 months after completion of last course of radiation, and are not taking corticosteroids for treatment of brain metastasis; patients with a prior history of brain metastases who meet other eligibility criteria
Central nervous system metastasis; Note: patients 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
Individuals with the presence of symptomatic central nervous system (CNS) metastasis requiring radiation, surgery, or ongoing use of corticosteroids; untreated or brain metastasis causing any symptoms; treated brain metastasis must be stable for 4 weeks prior to first dose of study drug and not requiring steroids for at least 7 days prior to study treatment
More than one brain metastasis (qualifying measurable brain lesions are any contrast enhancing metastases identifiable by the physician)
MRI scan consistent with brain metastasis as per radiology report
Untreated brain metastasis that may be considered active
Newly dignosed or active brain metastasis
Subject must have cytologically or histologically confirmed malignancy (this is the original malignancy, not the brain metastases); the largest measurable brain metastasis must be at least 1.0 cm in short axis dimension
Patients with brain metastasis will be included as long as they are free of neurologic symptoms related to metastatic brain lesions and who do not require or receive systemic corticosteroid therapy in the 14 days prior to beginning MK-3475 therapy
Extra-cranial metastasis
Patients with brain metastasis will be included as long as they are free of neurologic symptoms related to metastatic brain lesions and who do not require or receive systemic corticosteroid therapy in the 14 days prior to beginning ipilimumab therapy
Have extrahepatic metastasis.
Patients with known brain metastases are eligible only if he/she has been treated for brain metastasis, are asymptomatic after treatment, have a stable CT or MRI of the brain within 28 days of enrollment and are not receiving corticosteroid therapy to control symptoms from brain metastasis. Only a non-enzyme inducing anticonvulsant (e.g., Keppra) will be permitted for those patients requiring anticonvulsants. (Topical and/or inhaled steroids are allowed.)
Patients with documented central nervous system or leptomeningeal metastasis (brain metastasis) at the time of study entry; patients with prior brain metastasis may be considered if they have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic
A subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis at least 4 weeks prior to study registration, have been off of corticosteroids for >= 2 weeks, and are asymptomatic.
Patients with central nervous system (CNS) metastasis will be allowed on the study if the metastasis is treated, no clinical signs of metastasis progression following treatment, and the patient is off steroids for at least 3 days (only if steroids are prescribed specifically for brain metastasis)
One brain metastasis or brain metastasis resection cavity with maximal diameter >= 3 cm (or >= 14 cc) and =< 6 cm (or =< 113 cc)
Hepatic metastasis permissible; appropriate candidates with metastasis to liver may be considered for ablative hypofractionation using SBRT
Untreated brain metastasis
Patients with documented central nervous system or leptomeningeal metastasis (brain metastasis) at the time of study entry; patients with prior brain metastasis may be considered if they have completed their treatment for brain metastasis and no longer require corticosteroids
Patients with brain metastasis have no signs of progressive disease 4 months after the completion of brain metastasis treatment (radiation therapy, surgery, etc.) do not require anticonvulsants or corticosteroids, and have been off such drugs for at least 7 days
Extensive active brain disease including symptomatic brain metastases or the presence of leptomeningeal disease, and all patients with infratentorial tumors\r\n* Note: patients with brain metastasis after definitive therapy with surgery or stereotactic radiation and stable off steroids for > 4 weeks are eligible as are patients with asymptomatic brain metastasis as long as less than 1 cm and thus deemed as not requiring therapy by the primary physician and the lesions(s) are not infratentorial
Subjects with previously treated brain metastasis who are free of central nervous system (CNS) symptoms and are >= 14 days from treatment of brain metastasis are eligible; there must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration
Have active central nervous system (CNS) or leptomeningeal metastasis (brain metastasis) at the time of enrollment. Participants with a history of a CNS metastasis previously treated with curative intent (for example, stereotactic radiation or surgery) that have not progressed on follow-up imaging, have been asymptomatic for at least 60 days and are not receiving systemic corticosteroids and or/anticonvulsants, are eligible. Participants with signs or symptoms of neurological compromise should have appropriate radiographic imaging performed before enrollment to rule out brain metastasis.
Subject has active brain metastases or leptomeningeal metastases. Subjects with prior history of brain metastasis who have undergone local therapy (i.e., metastasectomy and/or radiation) and show no evidence of local recurrence or progression over the past 3 months prior to Screening are eligible.
Patients with uncontrolled brain metastases; patients with brain metastasis must be asymptomatic and off corticosteroid use for at least one week
Subjects with previously treated brain metastasis (es) that is asymptomatic or radiographically/clinically stable and not requiring steroids medications for 4 weeks prior to enrollment are permitted.
MRI detected active brain metastasis witch require other therapies such as surgery and/or radiation therapy. Patients already treated for their brain metastasis, surgery or radiation therapy, and have had stable disease for more than two month and NOT requiring steroids may however be included in this study.
Known active brain metastasis unless they have been treated and shown documented radiographic stability for 28 days
Subjects with known or suspected brain metastasis, or brain as the only site of disease are excluded with the following exceptions\r\n* Subjects with controlled brain metastasis (no radiographic progression at least 4 weeks following radiation and/or surgical treatment, off steroids for at least 4 weeks, and have no new or progressing neurological signs or symptoms) will be allowed\r\n* Subjects with a history of prior malignancy with the exception of carcinoma in situ of the cervix or other malignancy diagnosed > 2 years ago that has undergone potentially curative therapy with no evidence of disease for the last >= 2 years and that is deemed by the investigator to be at a low risk of recurrence
Presence of central nervous system metastasis (including active brain metastasis); active brain metastasis would be defined as untreated brain metastases; if the brain metastases have received prior treatment (usually either with surgery or radiation), they are no longer active
Active central nervous system (CNS) or leptomeningeal metastasis (brain metastasis) at the time of randomization. Participants with a history of a CNS metastasis previously treated with curative intent (for example, stereotactic radiation or surgery) that have not progressed on follow-up imaging, have been asymptomatic for at least 60 days and are not receiving systemic corticosteroids and or/anticonvulsants, are eligible. Participants with signs or symptoms of neurological compromise should have appropriate radiographic imaging performed before randomization to rule out brain metastasis.
Documented extracranial metastasis
If the patient has brain metastasis, they must have been stable (treated and/or asymptomatic) and the patient must have been off steroids for at least 2 weeks
Evidence of active brain metastasis including leptomeningeal involvement\r\n* CNS metastasis controlled by prior surgery and/or radiotherapy is allowed; NOTE: to be considered controlled, there must be at least 4 weeks of no clinical symptoms or evidence of progression prior to study entry and corticosteroid therapy must have been discontinued
presence of a space occupying lesion in the brain including previously treated brain metastasis(es) or primary central nervous system (CNS) tumor,
Patients must not have hemoptysis, squamous histology, brain metastasis
Patients with active brain metastases. Patients with prior history of brain metastasis who have undergone local therapy (i.e. metastatectomy and/or radiation) and show no evidence of local recurrence or progression over the past 6 months are eligible
Presence of life-limiting extra-hepatic metastasis that requires a systemic treatment within 3 months; patients with extra-hepatic metastasis that can be controlled with a loco-regional treatment are eligible
Patients with measurable brain metastasis outside a 5-mm margin around either hippocampus
Patients with brain metastasis that are unstable (i.e. presenting with neurologic symptoms that progress or require increasing doses of steroids within a 4-week period) or are untreated (i.e. not radiated) should be excluded
Patients with known intraparenchymal brain metastasis at study entry are excluded due to poor CNS penetration of SF1126.
Palliative radiation for treatment of painful bone metastasis, control of hemoptysis or treatment of small asymptomatic brain metastasis that become symptomatic during on protocol treatment is allowed; protocol treatment will be delayed until recovery from radiation at the discretion of the treating physician
Symptomatic brain metastasis or asymptomatic brain metastasis that are 1 cm or greater in size; patients with asymptomatic sub-centimeter brain metastasis are eligible
Bilirubin > 3 x ULN which cannot be attributed to MCC metastasis
Patients with any history of brain or bone metastasis or who have developed progressive disease on first line 5-FU based therapy
Has active brain metastasis or leptomeningeal carcinomatosis; patients with adequately treated brain metastases are eligible if they meet certain criteria
Patients must have no clinical evidence of active brain metastasis. Patients with a history of brain metastases must meet all of the following criteria:
Patients with more than a single brain metastasis ( >1 cm)
Patients may have a history of brain metastasis provided certain protocol criteria are met
Participant with a brain metastasis with symptoms or requiring treatment.
Active brain metastasis or treatment for brain metastasis within 1 month of scheduled dosing day 1. a. Dose of corticosteroid, if any, for brain metastasis must be tolerated in terms of glucose tolerance ? Grade 2 (symptomatic; dietary modification or oral agent indicated) and hyperglycemia ? Grade 2 (fasting glucose value >160 - 250 mg/dL [> 8.9
Recurrent and/or metastatic resectable colorectal cancer, including disease within the abdomen and pelvis with no evidence of extra-abdominal metastases; intra-abdominal disease includes: isolated hepatic metastasis/metastases (see next inclusion criteria point), isolated peritoneal metastasis, or a combination of hepatic and extrahepatic metastasis
Symptomatic brain metastasis. Patients previously treated or untreated for these conditions that are asymptomatic in the absence of corticosteroid and anti-epileptic therapy are allowed to enroll
Patients with brain metastasis treated or untreated, or other CNS disease
Subjects with brain metastasis or central nervous system (CNS) disease are considered eligible if the subject has not received radiation therapy for brain metastasis within 2 weeks of enrollment and has been on a stable dose of steroids for 2 or more weeks
Brain metastasis are excluded unless
Radiologic evidence of new and/or progressive brain metastasis (>= 10 mm in longest dimension) by magnetic resonance (MR) imaging of the brain
Subjects with known or suspected brain metastasis unless previously treated and without evidence of progression
Pulmonary or brain metastasis, liver metastasis is allowed if LFTs are not elevated
Presence of clinically apparent or suspected brain metastasis.
Subject has known active brain or leptomeningeal metastases. Subjects with prior history of brain metastasis who have undergone local therapy (i.e. metastatectomy and/or radiation) and show no evidence of local recurrence or progression over the past 3 months prior to screening are eligible.
Pathological or clinical/radiological diagnosis of a neoplasm, either primary (e.g., malignant glioma) or secondary (metastasis from systemic malignancy) with a history of brain radiation therapy
Subjects with radiographically suspected, histologically or cytologically confirmed primary brain tumors or brain metastasis are eligible
At least one brain metastasis must be >= 1 cm to allow adequate quantitative imaging measurement for DSC-PMR
OR confirmed or suspected recurrent brain cancer or brain metastasis for which the primary tumor has been histologically confirmed,
Patients with brain metastasis that have been treated, asymptomatic and off any steroid use are permitted for study
Patients with local regional recurrence only or brain only metastasis.
Have a history of brain metastasis provided that all of the following criteria are met: