comparing the radiopharmaceutical drug, [177lu]lu-dotatate, to standard of care treatment for patients with meningioma that has come back after prior treatment

Conditions: Intracranial Meningioma

Summary: this is an open-label, multicenter, randomized, phase 2 clinical study to evaluate the efficacy of \[177lu\]lu-dotatate in patients with progressive grade 1-3 intracranial meningioma.

study participants will be randomized by a 2:1 ratio to receive either \[177lu\]lu-dotatate or standard of care therapy as deemed appropriate by the local investigator. at time of progression, participants on the standard of care arm may cross-over to the \[177lu\]lu-dotatate alternative treatment arm.

Eligibility criteria:
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.

Keywords: momentum-1 meningioma advanced intracranial meningioma sstr2 radiopharmaceuticals theranostics radioligand therapy lu-dotatate lutathera