A Prospective, Phase II Study of Lutetium Lu 177 Dotatate (LUTATHERA®) in Patients With Inoperable, Progressive Meningioma After External Beam Radiation Therapy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Mayo Clinic
- 入组人数
- 42
- 试验地点
- 2
- 主要终点
- Progression-free survival - 6 months
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
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 SPECT/CT dosimetry on study.
干预措施: Positron Emission Tomography (Procedure)
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 SPECT/CT dosimetry on study.
干预措施: Biospecimen Collection (Procedure)
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 SPECT/CT dosimetry on study.
干预措施: Computed Tomography (Procedure)
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 SPECT/CT dosimetry on study.
干预措施: Single Photon Emission Computed Tomography (Procedure)
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 SPECT/CT dosimetry on study.
干预措施: Gallium Ga 68-DOTATATE (Radiation)
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 SPECT/CT dosimetry on study.
干预措施: Questionnaire Administration (Other)
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 SPECT/CT dosimetry on study.
干预措施: Magnetic Resonance Imaging (Procedure)
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 SPECT/CT dosimetry on study.
干预措施: Lutetium Lu 177 Dotatate (Drug)
结局指标
主要结局
Progression-free survival - 6 months
时间窗: At 6 months after starting treatment
Defined as the number of evaluable patients not having progressive disease or death within six months of the first day of treatment.
次要结局
- Overall survival(Up to 5 years)
- Progression free survival - overall(Up to 5 years)
- Incidence of adverse events(Up to 24 months)