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.