Comparing the Radiopharmaceutical Drug, [177Lu]Lu-DOTATATE, to Standard of Care Treatment for Patients With Meningioma That Has Come Back After Prior Treatment (MOMENTUM-1)

MOMENTUM-1: A Multicenter, Randomized, Open-Label, Phase II Study of [177LU]LU-DOTATATE in Adults With Progressive Intracranial Grade 1-3 Meningioma

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 Overview

• Status: Suspended
• Conditions: Intracranial Meningioma
• Intervention / Treatment: Drug: [177Lu]Lu-DOTATATE; Other: Standard of Care treatments

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.

• Study Type: Interventional
• Enrollment (Estimated): 153
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Irvine, California, United States, 92697
      • University of California, Irvine
    • La Jolla, California, United States, 92093
      • University of California San Diego - Moores Cancer Center
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist MD Anderson Cancer Center
    • Miami, Florida, United States, 33146
      • University of Miami
    • Miami, Florida, United States, 33176
      • Baptist Health Medical Group Oncology
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Piedmont Healthcare
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber/Harvard Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Rogel Cancer Center
  • New York
    • New York, New York, United States, 10016
      • NYU Lagone Health
  • North Carolina
    • Durham, North Carolina, United States, 22708
      • Duke University Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [177Lu]Lu-DOTATATE; Study participants receive [177Lu]Lu-DOTATATE	Drug: [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).; Other Names: Lutathera
Other: Control; Study participants receive Local Standard of Care (SOC) Therapy. Control Arm participants crossover to [177Lu]Lu-DOTATATE at progression	Other: 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.; Other Names: Avastin (bevacizumab), Afinitor (everolimus), Hydrea (hydroxyurea), Hydroxycarbamide (hydroxyurea), Sutent (sunitinib)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS defined as the time from randomization to date of disease progression per current RANO meningioma criteria or death, whichever occurs first	Assessed up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival at 6 months (PFS-6)	Proportion of participants alive without progression at 6 months assessed per RANO meningioma criteria	6 months
Overall Survival at 12 months (OS-12)	Proportion of participants alive at 12 months	12 months
Overall survival (OS)	Time from randomization to death from any cause	Assessed up to 4 years
Progression-free Survival after cross-over (PFS2)	Time from cross-over to disease progression per RANO meningioma criteria or death from any cause, whichever occurs first.	Assessed up to 4 years
Disease Control Rate (DCR)	Proportion of patients achieving complete response, partial response, minor response or stable disease as per RANO meningioma criteria	Assessed up to 4 years
Objective response rate (ORR)	Proportion of patients achieving complete or partial response as per RANO meningioma criteria.	Assessed up to 4 years
Number of participants by highest grade treatment-emergent adverse event (TEAE):	Number of participants experiencing the highest grade TEAE, graded according to CTCAE version 5.0 (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, Grade 5 = death related to adverse event).	Assessed up to 4 years
Number of participants who discontinue treatment due to TEAE	Number of participants who discontinue treatment as a result of treatment-emergent adverse events.	Assessed up to 4 years

Collaborators and Investigators

• Sponsor: RTOG Foundation, Inc.
• Collaborators: Novartis Pharmaceuticals
• Investigators: Principal Investigator: Sylvia C Kurz, MD, PhD, Yale University; Principal Investigator: Erik P Sulman, MD,PhD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): December 24, 2025
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2030

Study Registration Dates

• First Submitted: April 22, 2025
• First Submitted That Met QC Criteria: April 30, 2025
• First Posted (Actual): May 2, 2025

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Radioligand Therapy; Lutathera; Meningioma; Theranostics; Radiopharmaceuticals; SSTR2; MOMENTUM-1; Advanced Intracranial Meningioma; Lu-DOTATATE
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Meningioma; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Amides; Indoles; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Macrolides; Lactones; Pyrroles; Sirolimus; Urea; Sunitinib; Bevacizumab; Everolimus; Hydroxyurea; lutetium Lu 177 dotatate
• Other Study ID Numbers: RTOG 3523; CAAA601A1US13R (Other Identifier: Novartis Pharmaceuticals, Inc.)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No