Using Lutathera to treat inoperable, progressive meningioma after 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 study is testing if a radioactive drug called Lutathera can help people with inoperable and progressive meningiomas feel better after they've had radiation therapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 42 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Mayo Clinic (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Rochester, Minnesota)
• Trial ID: NCT04082520 on ClinicalTrials.gov

What this trial studies

This phase II trial investigates the effectiveness of Lutathera, a radioactive drug, in treating patients with inoperable and progressive meningiomas following external beam radiation therapy. The study aims to evaluate the drug's safety and efficacy by measuring progression-free survival rates at six months for patients with recurrent grade 1, 2, or 3 meningiomas. Additionally, the trial will assess overall survival, treatment toxicity, and the impact on patients' quality of life using various assessment tools. Imaging techniques such as MRI and PET will be utilized to monitor treatment response.

Who should consider this trial

Good fit: Ideal candidates include patients with recurrent, inoperable meningiomas who have previously undergone radiation therapy and show evidence of disease progression.

Not a fit: Patients with meningiomas that are operable or those who have not received prior radiation therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat meningiomas, potentially improving survival and quality of life.

How similar studies have performed: While Lutathera has shown promise in treating other neuroendocrine tumors, this specific application for meningiomas is novel and has not been extensively tested in prior studies.

Eligibility criteria

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

Where this trial is running

Rochester, Minnesota

• Mayo Clinic in Rochester — Rochester, Minnesota, United States (Recruiting)

Study contacts

• Principal investigator: Kenneth W. Merrell, MD — Mayo Clinic
• Study coordinator: Clinical Trials Referral Office

Conditions Grade 1 Meningioma; Grade 2 Meningioma; Grade 3 Meningioma; Recurrent Meningioma; Unresectable Meningioma