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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04082520
Recruitment Status : Not yet recruiting
First Posted : September 9, 2019
Last Update Posted : December 30, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Grade I Meningioma Grade II Meningioma Grade III Meningioma Recurrent Meningioma Unresectable Meningioma Radiation: Gallium Ga 68-DOTATATE Drug: Lutetium Lu 177 Dotatate Procedure: Magnetic Resonance Imaging Procedure: Positron Emission Tomography Other: Quality-of-Life Assessment Other: Questionnaire Administration Phase 2

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), 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 for up to 6 months in the absence of disease progression or unacceptable toxicity.

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 41 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective, Phase II Study of Lutetium Lu 177 Dotatate (LUTATHERA?) in Patients With Inoperable, Progressive Meningioma After External Beam Radiation Therapy
Estimated Study Start Date : February 15, 2020
Estimated Primary Completion Date : September 4, 2024
Estimated Study Completion Date : September 15, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment (gallium Ga 68-DOTATATE PET/MRI, Lutathera)
Patients receive gallium Ga 68-DOTATATE IV and undergo a PET/MRI before cycles 1 and 4. Patients then receive lutetium Lu 177 dotatate IV over 30-40 minutes. Cycles repeat every 8 for up to 6 months in the absence of disease progression or unacceptable toxicity.
Radiation: Gallium Ga 68-DOTATATE
Given IV
Other Names:
  • (68)Ga-DOTA-TATE
  • 68Ga-DOTATATE
  • Gallium-68 DOTA-DPhe1, Tyr3-octreotate

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: Magnetic Resonance Imaging
Undergo PET/MRI
Other Names:
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR Imaging
  • MRI
  • 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

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies




Primary Outcome Measures :
  1. Progression-free survival [ Time Frame: At 6 months after starting treatment ]
    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.


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: From the first day of treatment to death due to any cause, assessed up to 5 years ]
    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.

  2. Progression free survival [ Time Frame: From the first day of treatment to the earliest date documentation of disease progression, assessed up to 5 years ]
    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.

  3. Incidence of adverse events [ Time Frame: Up to 24 months ]
    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.


Other Outcome Measures:
  1. Change in quality of life (QOL) [ Time Frame: Baseline up to 5 years ]
    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. The QOL impact will be measured with differences from baseline to 6, 12 and 24 months in patient reported outcomes via the symptom scales (measurement of day to day level of function and health determined by the patient) from four combined surveys. Scale ranges from excellent to poor. No formal comparisons will be made among the cohorts.

  2. Change in quality of life (QOL) [ Time Frame: Baseline up to 5 years ]
    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 a Brief Fatigue Inventory questionnaire. 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. Response to questionnaire range from no fatigue to as bad as you can imagine. No formal comparisons will be made among the cohorts.

  3. Change in quality of life (QOL) [ Time Frame: Baseline up to 5 years ]
    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 the European Quality of Life Five Dimension Five Level questionnaire. Mobility, Self-care, Activity level, Pain/discomfort, and Anxiety/Depression will be measured by the patient. 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.

  4. Change in quality of life (QOL) [ Time Frame: Baseline up to 5 years ]
    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 the Mayo Patient Survey National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy Brain Symptom Index Questionnaire-24 (version 2) questionnaire. Response to questionnaire range from Not at all to Very much. 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.

  5. Local control [ Time Frame: Up to 5 years ]
    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.

  6. Duration of local control [ Time Frame: From start of therapy until date of first progression, assessed up to 5 years ]
    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.

  7. Objective response to treatment [ Time Frame: Up to 5 years ]
    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.

  8. Response rate by volumetric analysis [ Time Frame: Up to 5 years ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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) 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04082520


Locations
Layout table for location information
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Kenneth W. Merrell         
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Kenneth W Merrell Mayo Clinic

Additional Information:
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Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT04082520    
Other Study ID Numbers: MC1891
NCI-2019-05848 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1891 ( Other Identifier: Mayo Clinic )
P30CA015083 ( U.S. NIH Grant/Contract )
First Posted: September 9, 2019    Key Record Dates
Last Update Posted: December 30, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Meningioma
Neoplasms, Nerve Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Vascular Tissue
Meningeal Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases