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 cancer cells. The goal of this
study is to determine whether this drug is safe and effective in treating meningiomas that
progress after radiation treatment.
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), European Quality of Life Five Dimension Five Level
(EQ-5D-5L), 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 (McDonald 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 before
cycles 1 and 4. Patients then receive lutetium Lu 177 dotatate intravenously (IV) over 30-40
minutes. Cycles repeat every 8 weeks for up to 6 months in the absence of disease progression
or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years and
then annually for 3 years.
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
- 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)
- 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 of the study)
- 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
- Significant toxicity related to previous radiation therapy including radiation
necrosis, radiation optic neuropathy, or radiation retinopathy
- Optic nerve sheath meningioma, extracranial meningioma