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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT06955169
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

RTOG Foundation, Inc.
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Erik P Sulman, MD,PhDSylvia C Kurz, MD, PhD
Principal Investigator Affiliation NYU Langone HealthYale University
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, Industry
Overall Status Not yet recruiting
Countries
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Intracranial Meningioma
Additional Details

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.

Arms & Interventions

Arms

Experimental: [177Lu]Lu-DOTATATE

Study participants receive [177Lu]Lu-DOTATATE

Other: Control

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

Interventions

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: - 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.

Contact Information

This trial has no sites locations listed at this time. If you are interested in learning more, you can contact the trial's primary contact:

Sylvia C Kurz, MD,PhD

[email protected]

203-785-5616

For additional contact information, you can also visit the trial on clinicaltrials.gov.

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