Lutathera for the Treatment of Inoperable, Progressive Meningioma After External Beam Radiation Therapy

NCT ID: NCT04082520

Last Updated: 2025-12-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

41 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-04-14

Study Completion Date

2031-01-06

Brief Summary

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This phase II trial studies how well lutathera works in treating patients with meningioma that cannot be treated with surgery (inoperable) and is growing, spreading, or getting worse (progressive) after external beam radiation therapy. Lutathera is a radioactive drug administered in the vein that is designed to target and kill tumor cells. The goal of this study is to determine whether this drug is safe and effective in treating meningiomas that progress after radiation treatment. WHO Grade I and Cohort WHO II/III cohorts will be evaluated.

Detailed Description

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PRIMARY OBJECTIVES:

I. To estimate the efficacy of lutetium Lu 177 dotatate (LUTATHERA) treatment in patients with recurrent grade 1 meningioma as measured by 6-month progression-free survival (PFS) rate.

II. To estimate the efficacy of LUTATHERA treatment in patients with recurrent grade 2 or 3 meningioma as measured by 6-month PFS rate.

SECONDARY OBJECTIVES:

I. To determine the overall survival (by grade cohort) of patients with recurrent meningioma during or after treatment of LUTATHERA.

II. To determine the progression-free survival (by grade cohort) of patients with recurrent meningioma during or after treatment of LUTATHERA.

III. To determine the toxicity of LUTATHERA treatment in patients with recurrent meningioma.

CORRELATIVE RESEARCH OBJECTIVES:

I. To assess the impact of treatment on the patient's quality of life (QOL) using the Promise-10, Brief Fatigue Inventory (BFI), and Mayo Patient Survey National Comprehensive Cancer Network (NCCN)-Functional Assessment of Cancer Therapy (FACT) Brain Symptom Index Questionnaire-24 (FBrSI-24) (version 2) instruments.

II. To compare the response assessment between standard of care brain magnetic resonance imaging (MRI) and gallium Ga 68-DOTATATE (68Ga-DOTATATE) positron emission tomography (PET) imaging.

III. To determine the best objective response (Macdonald criteria) of patients with recurrent meningioma during or after treatment of LUTATHERA.

IV. To determine the duration of local control with death as a competing risk (by grade cohort) of patients with recurrent meningioma during or after treatment of LUTATHERA.

V. To perform a quantitative dosimetric analysis of radiation dose delivered with lutathera:

Va. To determine intratherapeutic dosimetry for the target meningioma; Vb. To correlate treatment response of lutathera with target dose received; Vc. To determine intratherapeutic dosimetry for kidneys and other abdominal organs.

OUTLINE:

Patients receive gallium Ga 68-DOTATATE intravenously (IV) and undergo a PET/MRI or PET/computed tomography (CT) before cycles 1 and 4. Patients then receive lutetium Lu 177 dotatate IV over 30-40 minutes. Treatment repeats every 8 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MRI on study and during follow-up, as well as blood sample collection and possible single photon emission computed tomography (SPECT)/CT dosimetry on study.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for up to 5 years.

Conditions

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Grade 1 Meningioma Grade 2 Meningioma Grade 3 Meningioma Recurrent Meningioma Unresectable Meningioma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (gallium Ga 68-DOTATATE PET/MRI, Lutathera)

Patients receive gallium Ga 68-DOTATATE IV and undergo a PET/MRI or PET/CT before cycles 1 and 4. Patients then receive lutetium Lu 177 dotatate IV over 30-40 minutes. Treatment repeats every 8 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MRI on study and during follow-up, as well as blood sample collection and possible SEPCT/CT dosimetry on study.

Group Type EXPERIMENTAL

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET/MRI

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Computed Tomography

Intervention Type PROCEDURE

Undergo PET/CT and/or SPECT/CT

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Single Photon Emission Computed Tomography

Intervention Type PROCEDURE

Undergo SPECT/CT

Gallium Ga 68-DOTATATE

Intervention Type RADIATION

Given IV

Lutetium Lu 177 Dotatate

Intervention Type DRUG

Given IV

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo PET/MRI

Interventions

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Positron Emission Tomography

Undergo PET/MRI

Intervention Type PROCEDURE

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

Computed Tomography

Undergo PET/CT and/or SPECT/CT

Intervention Type PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Single Photon Emission Computed Tomography

Undergo SPECT/CT

Intervention Type PROCEDURE

Gallium Ga 68-DOTATATE

Given IV

Intervention Type RADIATION

Lutetium Lu 177 Dotatate

Given IV

Intervention Type DRUG

Magnetic Resonance Imaging

Undergo PET/MRI

Intervention Type PROCEDURE

Other Intervention Names

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(68)Ga-DOTA-TATE 68Ga-DOTA-0-Tyr3-Octreotate 68Ga-DOTATATE Gallium Ga 68 Oxodotreotide Gallium Oxodotreotide Ga-68 Gallium-68 DOTA-DPhe1, Tyr3-octreotate 177 Lu-DOTA-TATE 177 Lu-DOTA-Tyr3-Octreotate 177Lu-DOTA0-Tyr3-Octreotate Lutathera Lutetium Lu 177 DOTA(0)-Tyr(3)-Octreotate Lutetium Lu 177-DOTA-Tyr3-Octreotate lutetium Lu 177-DOTATATE Lutetium Oxodotreotide Lu-177 Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan NMR Imaging NMRI Nuclear Magnetic Resonance Imaging Medical Imaging, Positron Emission Tomography PET PET Scan Positron Emission Tomography Scan Positron-Emission Tomography proton magnetic resonance spectroscopic imaging CAT CAT Scan Computed Axial Tomography (CAT) computed axial tomography computerized axial tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT SCAN tomography Biological Sample Collection Biospecimen Collected Specimen Collection Medical Imaging, Single Photon Emission Computed Tomography Single Photon Emission Tomography Single-Photon Emission Computed single-photon emission computed tomography SPECT SPECT imaging SPECT SCAN SPET ST tomography, emission computed, single photon Tomography, Emission-Computed, Single-Photon

Eligibility Criteria

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Inclusion Criteria

* Previous treatment for meningioma including surgery, when possible, and radiation therapy (conventional fractionated or radiosurgery). Pathologic confirmation of meningioma is not required for patients who are not surgical candidates and received radiation therapy based on magnetic resonance imaging (MRI) consistent with meningioma. Patients with prior surgery will have pathologic confirmation of meningioma with either formalin-fixed paraffin-embedded (FFPE) tumor block OR meningioma tissue slides available for submission to central pathology review
* Radiographic evidence of meningioma progression with measurable disease, defined as an increase in size of the measurable primary lesion on imaging by 15% or more (sum of the bidirectional measurements) in an approximate 6 month time period (i.e., calculated rate of growth 15% / 6 months based on available scans) or by the appearance of a new measurable lesion
* Previous treatment with either fractionated radiation therapy or stereotactic radiosurgery at the site of progressive meningioma, without safe option for further radiotherapy
* Willing to undergo 68Ga-DOTATATE PET imaging. 68Ga-DOTATATE PET imaging must be Krenning score must be a score of 2 or higher, suggesting somatostatin receptor expression, to be registered on the study. A PET/MRI is preferred, but PET/CT is permitted if a patient is not technically able to receive a PET/MRI or at the discretion of the primary investigator (PI).
* Measurable disease
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) =\< 2
* Absolute neutrophil count (ANC) \>= 1500/mm (obtained =\< 28 days prior to registration)
* Platelet count \>= 100,000/mm (obtained =\< 28 days prior to registration)
* Hemoglobin \>= 9.0 g/dL (obtained =\< 28 days prior to registration)
* Direct bilirubin \< 1.5 x upper limit of normal (ULN) (or total bilirubin =\< 3.0 x ULN with direct bilirubin =\< 1.5 x ULN in patients with well-documented Gilbert's syndrome) (obtained =\< 28 days prior to registration)
* Aspartate transaminase (AST) =\< 3 x ULN (obtained =\< 28 days prior to registration)
* Prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time (PTT) =\< 1.5 x ULN OR if patient is receiving anticoagulant therapy and PT or PTT is within therapeutic range of intended use of coagulants (obtained =\< 28 days prior to registration)
* Calculated creatinine clearance must be \>= 40 ml/min using the Cockcroft-Gault formula (obtained =\< 28 days prior to registration) using the Chronic Kidney Disease Epidemiology Collaboration (CDK-EPI) equation.
* Ability to complete questionnaire(s) by themselves or with assistance
* Provide written informed consent
* Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study) and it is highly recommend to see study staff in Radiation Oncology, Medical Oncology and/or Neuro-Oncology during the Event Monitoring Phase of the study.
* Until 21 SPECT/CT slots are filled, willing to undergo SPECT/CT imaging for dosimetry analysis.

Exclusion Criteria

* Eligibility for surgical or radiation treatment with curative intent
* Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:

* Pregnant women (NOTE: Patients with surgical sterilization or who have been post-menopausal for at least 2 years are excluded form pregnancy testing, but this must be documented.)
* Nursing women
* Men or women of childbearing potential who are unwilling to employ adequate contraception
* Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
* Contraindications to or intolerance of MRI
* Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy

* NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association \[NYHA\] II, III, IV), unstable angina pectoris, uncontrolled diabetes mellitus (fasting blood glucose \> 2 ULN), cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm

* Note: This includes treatment with somatostatin LAR within 4 weeks prior to enrollment, or any patient receiving treatment with short-acting octreotide that cannot be interrupted for greater than 24 hours before treatment
* Other active malignancy =\< 2 years prior to registration

* EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix
* NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer
* History of myocardial infarction =\< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
* Current spontaneous urinary incontinence making impossible the safe administration of LUTATHERA
* Untreated, refractory and/or symptomatic toxicity related to previous radiation therapy including radiation necrosis, radiation optic neuropathy, or radiation retinopathy
* Optic nerve sheath meningioma, extracranial meningioma
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mayo Clinic

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kenneth W. Merrell, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

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Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Clinical Trials Referral Office

Role: CONTACT

855-776-0015

Facility Contacts

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Clinical Trials Referral Office

Role: primary

855-776-0015

Related Links

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Other Identifiers

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NCI-2019-05848

Identifier Type: REGISTRY

Identifier Source: secondary_id

MC1891

Identifier Type: OTHER

Identifier Source: secondary_id

17-009927

Identifier Type: OTHER

Identifier Source: secondary_id

MC1891

Identifier Type: -

Identifier Source: org_study_id

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