Inclusion Criteria:

STEP 1 REGISTRATION

• Aged >= 18 years
• Histologically confirmed diagnosis of WHO grade 1-3 meningioma
• Presence of measurable contrast-enhancing disease on gadolinium-enhanced MRI brain scan defined as at least one lesion with two perpendicular diameters measuring ≥10 mm on two or more axial slices (≤ 5 mm interslice thickness, ≤ 1 mm interslice gap) per current RANO meningioma criteria
• Progression of disease determined by local radiology review per current RANO meningioma criteria, defined as
  • ≥ 15% increase in sum of product of perpendicular measurements of up to 3 measurable target lesions within the last 6 months, or
  • ≥ 25% increase in sum of product of perpendicular measurements of up to 3 measurable target lesions within the last 12 months, or
  • Development of a new measurable lesion
• The following scans must be available for submission for central radiology review:
  • Pre-progression gadolinium-enhanced MRI brain scan
  • Progression gadolinium-enhanced MRI brain scan

STEP 2 REGISTRATION

• Progression of disease determined by central radiology review per current RANO meningioma criteria, defined as
  • ≥ 15% increase in sum of product of perpendicular measurements of up to 3 measurable target lesions within the last 6 months, or
  • ≥ 25% increase in sum of product of perpendicular measurements of up to 3 measurable target lesions within the last 12 months, or
  • Development of a new measurable lesion.
• [68Ga]Ga-DOTATATE uptake on PET-CT. Positive uptake is defined as a Krenning score >= 3, based on the uptake in at least one target lesion, referenced to the uptake in the liver and spleen.
• If randomized to the control (standard of care) arm, both the patient and investigator must agree NOT to receive SSTR2-targeted therapy, surgical resection, or radiation therapy.
• Patients must be willing and able to undergo regular MRI scans of the brain and [68Ga]Ga-DOTATATE PET-CT imaging during the study.
• Patients must have recovered to CTCAE grade ≤1 or pretreatment baseline from clinically significant adverse events related to prior therapy (exclusions include alopecia, lymphopenia, sensory neuropathy ≤ grade 2, or other ≤ grade 2 not constituting a safety risk based on the investigator's judgment).
• Adequate organ and bone marrow function as defined below (within 28 days prior to step 2 registration):
  • Absolute neutrophil count (ANC) ≥ 1500/mm3
  • Platelet count ≥ 75,000/mm3
  • Hemoglobin ≥ 8 g/dL
  • Creatinine clearance (calculated by the Cockroft-Gault method) ≥40mL/min
  • Total serum bilirubin ≤ 3 x ULN (except participants with Gilbert's Syndrome, who can have a total bilirubin ≤ 5 x ULN)
  • Potassium within normal limits.

Exclusion Criteria:

• Patients with a clinical diagnosis of NF2-related schwannomatosis or with a known molecular diagnosis of NF2-related schwannomatosis.
• Patients with radiation-associated meningiomas.
• Patients with known intraspinal meningiomas or meningioma metastases outside the skull/spinal column.
• Prior SSTR2-targeted therapy, e.g. Somatostatin LAR or short-acting Octreotide.
• Unstable neurological symptoms requiring steroids to control symptoms at a dose of >2 mg of dexamethasone (or equivalent) daily within 28 days prior to step 2 registration.
• Patients requiring immediate local therapy (e.g. surgical resection).
• Surgical procedure within the timeframes listed below, prior to step 2 registration.
  • 28 days from any prior craniotomy
  • 7 days from stereotactic biopsy Note: There is no limit to the number of prior surgical interventions
• Treatment within the timeframes specified below, prior to step 2 registration.
  • 28 days (or 5 half-lives, whichever is longer) for cytotoxic chemotherapy, biologic agent, investigational agent or any other systemic agent prescribed for the purpose of treating meningioma
  • 6 weeks from nitrosoureas Note: There is no limit to the number of prior systemically administered therapeutic agents.
• Prior external beam radiation, interstitial brachytherapy or stereotactic radiosurgery cumulative radiation dose of > 70 Gy or the last dose of radiotherapy < 24 weeks (6 months) prior to step 2 registration
• Peptide receptor radionuclide therapy at any time prior to registration.
• Known hypersensitivity to somatostatin analogues or any component of the [68Ga]Ga- DOTATATE or [177Lu]Lu-DOTATATE formulations.
• Active infection requiring current use of intravenous therapy with antibiotics.
• Active cardiovascular disease: cerebral vascular accident/stroke (≤ 6 months prior to registration), myocardial infarction (≤ 6 months prior to registration), congestive heart failure (≥ NYHA class II), unstable angina pectoris, or serious cardiac arrhythmia requiring medication.
• An active malignancy ≤ 3 years. Note: Patients with a malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Pregnant and/or breastfeeding patients who are unwilling to discontinue breast feeding.
• Participants of childbearing potential must have a negative pregnancy test within 14 days of study entry.