Clinical Trials /

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

NCT04082520

Description:

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.

Related Conditions:
  • Meningioma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Lutathera for the Treatment of Inoperable, Progressive Meningioma After External Beam Radiation Therapy
  • Official Title: A Prospective, Phase II Study of Lutetium Lu 177 Dotatate (LUTATHERA?) in Patients With Inoperable, Progressive Meningioma After External Beam Radiation Therapy

Clinical Trial IDs

  • ORG STUDY ID: MC1891
  • SECONDARY ID: NCI-2019-05848
  • SECONDARY ID: MC1891
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT04082520

Conditions

  • Grade I Meningioma
  • Grade II Meningioma
  • Grade III Meningioma
  • Recurrent Meningioma
  • Unresectable Meningioma

Interventions

DrugSynonymsArms
Lutetium Lu 177 Dotatate177 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-177Treatment (gallium Ga 68-DOTATATE PET/MRI, Lutathera)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (gallium Ga 68-DOTATATE PET/MRI, Lutathera)ExperimentalPatients 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.
  • Lutetium Lu 177 Dotatate

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) 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival
Time Frame:At 6 months after starting treatment
Safety Issue:
Description: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

Measure:Overall survival
Time Frame:From the first day of treatment to death due to any cause, assessed up to 5 years
Safety Issue:
Description: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.
Measure:Progression free survival
Time Frame:From the first day of treatment to the earliest date documentation of disease progression, assessed up to 5 years
Safety Issue:
Description: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.
Measure:Incidence of adverse events
Time Frame:Up to 24 months
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Mayo Clinic

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