Comparing the Radiopharmaceutical Drug, [177Lu]Lu-DOTATATE, to Standard of Care Treatment for Patients With Meningioma That Has Come Back After Prior Treatment

NCT ID: NCT06955169

Last Updated: 2025-11-13

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 153 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-11-30
• Study Completion Date: 2030-08-31

Brief 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.

Detailed Description

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.

Conditions

Intracranial Meningioma

Keywords

MOMENTUM-1; Meningioma; Advanced Intracranial Meningioma; SSTR2; Radiopharmaceuticals; Theranostics; Radioligand Therapy; Lu-DOTATATE; Lutathera

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

[177Lu]Lu-DOTATATE

Study participants receive \[177Lu\]Lu-DOTATATE

Group Type: EXPERIMENTAL

[177Lu]Lu-DOTATATE

Intervention Type: DRUG

The treatment regimen consists of 4 (+2 optional) administrations of \[177Lu\]Lu-DOTATATE. The recommended interval between infusions is 4 weeks (+ 7 days).

Control

Study participants receive Local Standard of Care (SOC) Therapy. Control Arm participants crossover to \[177Lu\]Lu-DOTATATE at progression

Group Type: OTHER

Standard of Care treatments

Intervention Type: OTHER

Treatments will occur at the discretion and based on clinical judgement of the local and treating investigator. Local SOC therapy with one of the following agents: bevacizumab, everolimus, hydroxyurea, or sunitinib.

Interventions

[177Lu]Lu-DOTATATE

The treatment regimen consists of 4 (+2 optional) administrations of \[177Lu\]Lu-DOTATATE. The recommended interval between infusions is 4 weeks (+ 7 days).

Intervention Type: DRUG

Standard of Care treatments

Treatments will occur at the discretion and based on clinical judgement of the local and treating investigator. Local SOC therapy with one of the following agents: bevacizumab, everolimus, hydroxyurea, or sunitinib.

Intervention Type: OTHER

Other Intervention Names

Lutathera; Avastin (bevacizumab), Afinitor (everolimus), Hydrea (hydroxyurea), Hydroxycarbamide (hydroxyurea), Sutent (sunitinib)

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 5 measurable target lesions within the last 6 months, or
• ≥ 25% increase in sum of product of perpendicular measurements of up to 5 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 5 measurable target lesions within the last 6 months, or
• ≥ 25% increase in sum of product of perpendicular measurements of up to 5 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 uptake at least as high as liver, based on the uptake in at least one target lesion.
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

RTOG Foundation, Inc.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Erik P Sulman, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

NYU Langone Health

Sylvia C Kurz, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Central Contacts

Sylvia C Kurz, MD,PhD

Role: CONTACT

Phone: 203-785-5616

Email: Sylvia.Kurz@yale.edu

Other Identifiers

CAAA601A1US13R

Identifier Type: OTHER

Identifier Source: secondary_id

RTOG 3523

Identifier Type: -

Identifier Source: org_study_id