Clinical Trials /

Phase II Study of 177Lu-DOTATATE Radionuclide in Adults With Progressive or High-risk Meningioma

NCT03971461

Description:

This single arm, open-label study will evaluate the efficacy of Lutathera (177Lu-DOTATATE) administered intravenously every 8 weeks for a total of 4 doses in patients with progressive WHO I-III or residual high-risk Ga-DOTATATE PET-MRI positive meningioma. Ga-DOTATATE PET-MRI scans will be obtained prior to initiation of Lutathera treatment and 6 months after the initiation of Lutathera treatment. The latter will be performed within the 14 days prior to the last dose of Lutathera treatment.

Related Conditions:
  • Grade I Meningioma
  • Grade II Meningioma
  • Grade III Meningioma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Single Arm, Open-label, Multicenter Phase II Study of 177Lu-DOTATATE Radionuclide in Adults With Progressive or High-risk Meningioma
  • Official Title: A Single Arm, Open-label, Multicenter Phase II Study of 177Lu-DOTATATE Radionuclide in Adults With Progressive or High-risk Meningioma

Clinical Trial IDs

  • ORG STUDY ID: 18-00719
  • NCT ID: NCT03971461

Conditions

  • Meningioma

Interventions

DrugSynonymsArms
Lutathera177Lu-DOTATATELutathera

Purpose

This single arm, open-label study will evaluate the efficacy of Lutathera (177Lu-DOTATATE) administered intravenously every 8 weeks for a total of 4 doses in patients with progressive WHO I-III or residual high-risk Ga-DOTATATE PET-MRI positive meningioma. Ga-DOTATATE PET-MRI scans will be obtained prior to initiation of Lutathera treatment and 6 months after the initiation of Lutathera treatment. The latter will be performed within the 14 days prior to the last dose of Lutathera treatment.

Trial Arms

NameTypeDescriptionInterventions
LutatheraExperimental
  • Lutathera

Eligibility Criteria

        Inclusion Criteria:

          -  Karnofsky Performance Status ≥ 60.

          -  Histologically confirmed diagnosis WHO grade I-III meningioma:

          -  For grade I meningioma, subjects must have:

          -  Progressive disease after at least surgical resection and radiotherapy, as defined as
             an increase in size of the measurable primary lesion (bidirectional area) on imaging
             by 25% or more between scans separated by no more than 24 months.

          -  Progressive residual tumor after maximal safe resection, be located at or near
             critical organs at-risk [24] and considered to be high-risk for radiation injury by
             the treating investigator. Prior external beam radiotherapy is not required for these
             subjects.

          -  For Grade II or III meningioma, subjects must have either:

          -  Progressive disease after at surgical resection and radiotherapy, as defined as an
             increase in size of the measurable primary lesion (bi-directional area) on imaging by
             25% or more between scans separated by no more than 24 months

          -  Residual measurable disease after surgery without requirement of progression.

          -  Positive 68Ga-DOTATATE uptake on PET-MRI.

          -  Positive uptake is defined as uptake higher than the background and SUV ratios
             adjusted to the liver and spleen uptake (adopted from Krenning score).25

          -  Presence of measurable disease defined as at least one lesion measuring ≥10 mm in at
             least one dimension by contrast-enhanced MRI performed within 30 days prior to study
             registration.

          -  Multifocal disease, meningioma with extra-cranial spread, spinal meningiomas, and
             metastatic meningiomas (as defined by extracranial meningiomas) are allowed.

          -  There is no limit on the number of prior surgeries, radiation therapy, radiosurgery
             treatments or systemically administered therapeutic agents.

          -  For patients treated with external beam radiation, interstitial brachytherapy or
             radiosurgery, an interval ≥24 weeks must have elapsed from completion from these
             therapies to registration unless there is histopathologic confirmation of recurrent
             tumor or there is new enhancing tumor outside the radiation field (beyond the high
             dose region or the 80% isodose line).

          -  An interval of ≥28 days (or 5 half-lives, whichever is shorter) from prior cytotoxic
             chemotherapy (6 weeks from nitrosoureas), biologic agent, investigational agent or any
             other systemic agent prescribed for the purpose of treating meningioma.

          -  An interval of ≥28 days from craniotomy and ≥7 days from stereotactic biopsy.

          -  Availability of a paraffin-embedded archival tumor block sufficient to generate at
             least 25 unstained slides; or, if a paraffin tumor block is unavailable, at least 25
             unstained slides.

          -  Patients must be willing and able to undergo regular MRI scans of the brain.

          -  Patients must have recovered to CTCAE grade ≤1 or pretreatment baseline from
             clinically significant adverse events related to prior therapy (exclusions include
             alopecia, laboratory values listed per inclusion criteria, lymphopenia, sensory
             neuropathy ≤ grade 2, or other ≤ grade 2 not constituting a safety risk based on the
             investigator's judgment).

          -  Adequate organ and bone marrow function as defined below (within 21 days of treatment
             initiation):

          -  Women of childbearing potential (WOCBP) and men able to father a child must agree to
             use adequate contraception (hormonal or barrier method of birth control, abstinence)
             prior to study entry and for the duration of study participation. Should a woman
             become pregnant or suspect she is pregnant while participating in the study, she must
             inform her treating physician immediately.

          -  Able to understand and willing to sign an IRB approved written informed consent
             document.

        Exclusion Criteria:

          -  Participants with a clinical diagnosis of NF2 (either by NIH or Manchester criteria)
             or with a molecular diagnosis of NF2.

          -  Receiving any other investigational agent which would be considered as a treatment for
             the primary neoplasm. This includes treatment with Somatostatin LAR within 4 weeks
             prior to treatment, or any patient receiving treatment with short-acting Octreotide
             that cannot be interrupted for greater than 24 hours before treatment.

          -  Peptide receptor radionuclide therapy at any time prior to registration.

          -  Known hypersensitivity to somatostatin analogues or any component of the 68Ga-
             DOTATATE or 177Lu-DOTATATE formulations.

          -  Known additional malignancy that is progressing or requires active treatment within 2
             years of start of study drug. Exceptions include basal cell carcinoma of the skin,
             squamous cell carcinoma of the skin, and in situ cervical cancer that has undergone
             potentially curative therapy.

          -  Current or planned participation in another study of an investigational agent or
             investigational device.

          -  Active infection requiring intravenous therapy with antibiotics.

          -  Uncontrolled intercurrent illness including, but not limited to, clinically
             significant (i.e. active) cardiovascular disease: cerebral vascular accident/stroke (<
             6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment),
             congestive heart failure (≥ NYHA class II), unstable angina pectoris, or serious
             cardiac arrhythmia requiring medication.

          -  Known history of testing positive for human immunodeficiency virus (HIV) or known
             acquired immunodeficiency syndrome (AIDS).

          -  Active Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening
             (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test is
             positive).

          -  Other severe acute or chronic medical or psychiatric conditions (within the past year)
             including recent or active suicidal ideation or behavior, or laboratory abnormalities
             that may increase the risk associated with study participation or treatment on study
             or may interfere with the interpretation of study results.

          -  Pregnant and/or breastfeeding patients. Women of childbearing potential (WOCBP) must
             have a negative pregnancy test within 14 days of study entry.
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival at 6 months (PFS-6)
Time Frame:6 Months
Safety Issue:
Description:proportion of subjects who achieve a complete response (CR), partial response (PR), or stable disease (SD) at 6 months from start of Lutathera treatment. Radiographic treatment response will be assessed by measuring the bidirectional tumor diameters on contrast-enhanced MRI in patients who received at least one dose of Lutathera compared to baseline measurements at time of study enrollment

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:12 months
Safety Issue:
Description:defined as the best response [Complete Response (CR) + Partial Response (PR) + stable disease (SD)] recorded from the start of the study until the end of study in patients who received at least one dose of Lutathera.
Measure:Overall Survival at 12 months (OS-12)
Time Frame:12 months
Safety Issue:
Description:proportion of subjects who are alive at 12 months from start of Lutathera treatment. Survival data will be captured by clinical follow-up every 8 weeks during treatment with Lutathera and by follow-up phone calls every 12 weeks for up to 2 years after completion of treatment with Lutathera.
Measure:Progression Free Survival (PFS)
Time Frame:2 Years Post Treatment
Safety Issue:
Description:defined as the number of days from the treatment start date to the date of documented disease progression or death due to any cause.
Measure:Overall Survival (OS)
Time Frame:2 Years Post Treatment
Safety Issue:
Description:defined as the number of days from the treatment start date to the date of death due to any cause.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:NYU Langone Health

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