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

A Prospective, Phase II Study of Lutetium Lu 177 Dotatate (LUTATHERA®) in Patients With Inoperable, Progressive Meningioma After External Beam Radiation Therapy

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.

Study Overview

• Status: Recruiting
• Conditions: Grade 1 Meningioma; Grade 2 Meningioma; Grade 3 Meningioma; Recurrent Meningioma; Unresectable Meningioma
• Intervention / Treatment: Other: Questionnaire Administration; Procedure: Biospecimen Collection; Drug: Lutetium Lu 177 Dotatate; Procedure: Single Photon Emission Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Radiation: Gallium Ga 68-DOTATATE; Procedure: Computed Tomography

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic in Rochester
      • Principal Investigator: Kenneth W. Merrell, M.D.
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 enrolled 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 =< 14 days prior to registration)
• Platelet count >= 100,000/mm (obtained =< 14 days prior to registration)
• Hemoglobin >= 9.0 g/dL (obtained =< 14 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 =< 14 days prior to registration)
• Aspartate transaminase (AST) =< 3 x ULN (obtained =< 14 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 =< 14 days prior to registration)
• Calculated creatinine clearance must be >= 40 ml/min using the Cockcroft-Gault formula (obtained =< 14 days prior to registration) using the Chronic Kidney Disease Epidemiology Collaboration (CDK-EPI) equation.

• Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only

  • NOTE: A negative pregnancy test needs to be done within 48 hours of receiving LUTATHERA treatment
  • NOTE: Patients with surgical sterilization or who have been post-menopausal for at least 2 years are excluded from pregnancy testing, but this must be documented
• 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 and the Event Monitoring Phase of the study) and it is highly recommend seeing study staff in Radiation Oncology, Medical Oncology and/or Neuro-Oncology.

• Willing to sign consent onto the Mayo Clinic Radiotherapy Patient Outcomes Registry and Biobanking study, IRB number 15-000136

  • NOTE: The blood draw is optional

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
  • 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Other: Questionnaire Administration; Ancillary studies; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Drug: Lutetium Lu 177 Dotatate; Given IV; Other Names: 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; Procedure: Single Photon Emission Computed Tomography; Undergo SPECT/CT; Other Names: ST; Medical Imaging, Single Photon Emission Computed Tomography; Single Photon Emission Tomography; single-photon emission computed tomography; SPECT; SPECT imaging; SPECT SCAN; SPET; tomography, emission computed, single photon; Tomography, Emission-Computed, Single-Photon; Single-Photon Emission Computed; Procedure: Magnetic Resonance Imaging; Undergo PET/MRI; Other Names: MRI; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Undergo PET/MRI; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; Radiation: Gallium Ga 68-DOTATATE; Given IV; Other Names: (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; Procedure: Computed Tomography; Undergo PET/CT and/or SPECT/CT; Other Names: CT; CAT; CAT Scan; Computerized Tomography; tomography; CT SCAN; computerized axial tomography; Computerized axial tomography (procedure); Computed Axial Tomography (CAT); Computerized Tomography (CT) scan; computed axial tomography

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Will be defined as the number of evaluable patients not having progressive disease or death within six months of the first day of treatment divided by the total number of evaluable patients. The proportion of successes in each cohort will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Clopper-Pearson. There will be no formal comparison of rates among the two different grade cohorts of patients.	At 6 months after starting treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	The distribution of survival time for both cohorts will be estimated using the method of Kaplan-Meier. No formal comparison will be made among the cohorts.	From the first day of treatment to death due to any cause, assessed up to 5 years
Progression free survival	The distribution of time to progression will be estimated using the method of Kaplan-Meier (Kaplan et. al 1958). No formal comparison will be made among the cohorts.	From the first day of treatment to the earliest date documentation of disease progression, assessed up to 5 years
Incidence of adverse events	Will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.	Up to 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local control	Will be defined as a best objective response of stable disease, partial or complete response to treatment as determined by Macdonald Criteria. The proportion of patients who have achieved local control will be summarized by cohort and 95% confidence intervals calculated according to the methods described in Clopper-Pearson. No formal comparison will be made among the cohorts.	Up to 5 years
Duration of local control	The distribution of local control and survival without progression as a competing risk model will be constructed using Kaplan-Meier estimates. No formal comparisons will be made amongst the cohorts.	From start of therapy until date of first progression, assessed up to 5 years
Objective response to treatment	Will be determined by Macdonald Criteria. The proportion of patients in each response category will be summarized by cohort and 95% confidence intervals calculated according to the methods described in Clopper-Pearson. No formal comparison will be made among the cohorts.	Up to 5 years
Response rate by volumetric analysis	The response rate determined by volumetric analysis will be estimated for each cohort with proportion of patients who achieve complete response/partial response deemed by volumetric analysis. The 90% two-sided confidence intervals will be calculated according to approach of Clopper-Pearson. No formal comparison will be made among the cohorts.	Up to 5 years
Change in quality of life (QOL)	QOL will be measured using the standard survey series for this population of patients, and QOL trajectory over time will be examined. The survey series includes Promise-10, Brief Fatigue Inventory, and Mayo Patient Survey National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy Brain Symptom Index Questionnaire-24 (version 2). The main QOL impact will be measured with differences from baseline to 6, 12 and 24 months in patient reported outcomes via the symptom scales from the above surveys. All other QOL analyses will be exploratory and may include change from baseline to all time points using t-test and generalized linear models to test for changes at each time point and non-zero slopes, respectfully. No formal comparisons will be made among the cohorts.	Baseline up to 5 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Kenneth W. Merrell, M.D., Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2020
• Primary Completion (Estimated): September 4, 2024
• Study Completion (Estimated): September 4, 2025

Study Registration Dates

• First Submitted: September 4, 2019
• First Submitted That Met QC Criteria: September 5, 2019
• First Posted (Actual): September 9, 2019

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Meningioma; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Lutetium Lu 177 dotatate
• Other Study ID Numbers: MC1891 (Other Identifier: Mayo Clinic in Rochester); NCI-2019-05848 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 17-009927 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

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