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Male or female subjects aged ≥ 18 years |
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Karnofsky Performance Status ≥ 60 |
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Histologically confirmed diagnosis WHO grade I-III meningioma |
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For grade I meningioma, subjects must have: i. Progressive disease after at least surgical resection and radiotherapy, as defined as an increase in size of the measurable primary lesion (bidirectional area) on imaging by 25% or more between scans separated by no more than 12 months |
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or ii. Progressive residual tumor after maximal safe resection, be located at or near |
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critical organs at-risk and considered to be high-risk for radiation injury by the |
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treating investigator. Prior external beam radiotherapy is not required for these |
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subjects |
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b. For Grade II or III meningioma, subjects must have either: i. Progressive disease |
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after at least surgical resection and radiotherapy, as defined as an increase in size |
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of the measurable primary lesion (bi-directional area) on imaging by 25% or more |
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between scans separated by no more than 12 months or ii. Residual measurable disease |
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after surgery without requirement of progression |
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Positive 68Ga-DOTATATE uptake on PET-MRI |
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Positive uptake is defined as uptake higher than the background and SUV ratios |
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adjusted to the liver and spleen uptake (adopted from Krenning score) |
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68Ga-DOTATATE uptake in target lesions should be Krenning score ≥ 2 |
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Presence of measurable disease defined as at least one lesion measuring ≥10 mm in at |
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least one dimension by contrast-enhanced MRI performed within 30 days prior to study |
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registration |
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Multifocal disease is allowed but is limited to ≤ 3 measurable intracranial mass |
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lesions on the most recent post-contrast MRI |
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Any neurological symptoms must be stable for at least 28 days prior to enrollment and |
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patients should not require steroids to control neurological symptoms |
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There is no limit on the number of prior surgeries, radiation therapy, radiosurgery |
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treatments or systemically administered therapeutic agents |
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Patients must be willing and able to undergo regular MRI scans of the brain |
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For patients treated with external beam radiation, interstitial brachytherapy or |
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radiosurgery, an interval ≥24 weeks must have elapsed from completion from these |
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therapies to registration unless there is histopathologic confirmation of recurrent |
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tumor or there is new enhancing tumor outside the radiation field (beyond the high |
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dose region or the 80% isodose line) |
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An interval of ≥28 days (or 5 half-lives, whichever is shorter) from prior cytotoxic |
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chemotherapy (6 weeks from nitrosoureas), biologic agent, investigational agent or any |
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other systemic agent prescribed for the purpose of treating meningioma |
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An interval of ≥28 days from craniotomy and ≥7 days from stereotactic biopsy |
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Availability of a paraffin-embedded archival tumor block from most recent tumor |
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resection sufficient to generate at minimum 8 unstained slides but preferably up to 25 |
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unstained slides; or, if a paraffin tumor block is unavailable, at minimum 8 unstained |
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slides but preferably up to 25 unstained slides |
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a. Positive SSTR2 expression in the most recent tumor specimen must be confirmed by |
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central pathology review |
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Patients must have recovered to CTCAE grade ≤1 or pretreatment baseline from |
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clinically significant adverse events related to prior therapy (exclusions include |
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alopecia, laboratory values listed per inclusion criteria, lymphopenia, sensory |
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neuropathy ≤ grade 2, or other ≤ grade 2 not constituting a safety risk based on the |
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investigator's judgment) |
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Adequate organ and bone marrow function as defined below (within 21 days of treatment |
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initiation) |
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White blood cell (WBC) ≥ 2,000/mm3 |
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Absolute neutrophil count (ANC) ≥ 1,000/mm3 |
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Platelet count ≥ 75,000/mm3 |
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Hemoglobin ≥ 8 gm/dL |
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AST(SGOT)/ALT(SGPT) ≤ 3 x laboratory upper limit of normal (ULN) |
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Creatinine clearance (measured or calculated) ≥ 50 mL/min OR creatinine levels > |
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μMol/L (1.7 mg/dL) |
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Total serum bilirubin ≤ 3 X ULN (except participants with Gilbert's Syndrome, who |
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can have a total bilirubin ≤ 5 X ULN) |
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Serum albumin level of more than 3.0 g/dL, unless the prothrombin time value was |
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within the normal range |
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Women of childbearing potential (WOCBP) and men able to father a child must agree to |
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use adequate contraception (hormonal or barrier method of birth control, abstinence) |
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prior to study entry and for the duration of study participation. Should a woman |
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become pregnant or suspect she is pregnant while participating in the study, she must |
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inform her treating physician immediately |
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Able to understand and willing to sign an IRB approved written informed consent |
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document |
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Patients with radiation-associated meningiomas
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Peptide receptor radionuclide therapy at any time prior to registration
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Active infection requiring intravenous therapy with antibiotics
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Patients with a clinical diagnosis of NF2 (either by NIH or Manchester criteria) or
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with a molecular diagnosis of NF2
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Receiving any other investigational agent which would be considered as a treatment for
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the primary neoplasm. This includes treatment with Somatostatin LAR within 4 weeks
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prior to treatment, or any patient receiving treatment with short-acting Octreotide
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that cannot be interrupted for greater than 24 hours before treatment
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Known hypersensitivity to somatostatin analogues or any component of the 68Ga-
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DOTATATE or 177Lu-DOTATATE formulations
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Known additional malignancy that is progressing or requires active treatment within 2
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years of start of study drug. Exceptions include basal cell carcinoma of the skin
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squamous cell carcinoma of the skin, and in situ cervical cancer that has undergone
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potentially curative therapy
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Current or planned participation in another study of an investigational agent or
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investigational device
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Uncontrolled intercurrent illness including, but not limited to, clinically
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significant (i.e. active) cardiovascular disease: cerebral vascular accident/stroke (<
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months prior to enrollment), myocardial infarction (< 6 months prior to enrollment)
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congestive heart failure (≥ NYHA class II), unstable angina pectoris, or serious
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cardiac arrhythmia requiring medication
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Known history of testing positive for human immunodeficiency virus (HIV) or known
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acquired immunodeficiency syndrome (AIDS)
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Active Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening
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(positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test is
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positive)
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Other severe acute or chronic medical or psychiatric conditions (within the past year)
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including recent or active suicidal ideation or behavior, or laboratory abnormalities
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that may increase the risk associated with study participation or treatment on study
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or may interfere with the interpretation of study results
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Pregnant and/or breastfeeding patients. Women of childbearing potential (WOCBP) must
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have a negative pregnancy test within 14 days of study entry
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