Clinical Trials /

131I-omburtamab Radioimmunotherapy for Neuroblastoma Central Nervous System/Leptomeningeal Metastases

NCT03275402

Description:

Children with a neuroblastoma diagnose and central nervous system (CNS)/leptomeningeal metastases will be given up to 2 rounds of intracerebroventricular treatment with a radiolabelled monoclonal antibody, 131I-omburtamab to evaluate efficacy and safety

Related Conditions:
  • Neuroblastoma
Recruiting Status:

Recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 131I-omburtamab Radioimmunotherapy for Neuroblastoma Central Nervous System/Leptomeningeal Metastases
  • Official Title: A Multicenter Phase 2/3 Trial of the Efficacy and Safety of Intracerebroventricular Radioimmunotherapy Using 131I-omburtamab for Neuroblastoma Central Nervous System/Leptomeningeal Metastases

Clinical Trial IDs

  • ORG STUDY ID: 101
  • NCT ID: NCT03275402

Conditions

  • Neuroblastoma
  • CNS Metastases
  • Leptomeningeal Metastases

Interventions

DrugSynonymsArms
131I-omburtamab131I-8H9131I-omburtamab

Purpose

Children with a neuroblastoma diagnose and central nervous system (CNS)/leptomeningeal metastases will be given up to 2 rounds of intracerebroventricular treatment with a radiolabelled monoclonal antibody, 131I-omburtamab to evaluate efficacy and safety

Detailed Description

      One 131I-omburtamab treatment cycle takes 5 weeks and includes a dosimetry dose, a treatment
      dose, an observation period and post-treatment evaluations.

        -  A dosimetry dose (2mCi) of 131I-omburtamab is administered during week 1 followed by
           blood/cerebral spinal fluid (CSF) samples and whole-body scintigraphy at predefined
           intervals during the following 48 hours after treatment.

        -  A therapeutic dose (50mCi) of 131I-omburtamab is administered during week 2 followed by
           a 3-week observation period that includes a repeated MRI, CSF cytology, and safety
           monitoring.

        -  A second treatment cycle of 131I-omburtamab is administered during week 6 if there is no
           objective disease progression week 5 after the first injection, and the participant is
           presenting without unexpected and clinical significant Grade 4 toxicity. For
           participants with ongoing Grade 3 toxicity a second doing cycle will take place
           according to the discretion of the investigator.

      Participants can be treated in an outpatient setting or may be admitted as inpatients for
      both the dosimetry and the therapeutic injections.

      Participants completing at least one treatment period will first enter a follow-up period
      through week 26 and thereafter the long-term follow-up where patients will be evaluated for
      up to 3 years post-131I-omburtamab treatment where after the trial is ended

      Participants will be monitored for adverse events during and after 131I-omburtamab injection
      and will have pre- and post-treatment clinical assessments including neurologic examination,
      hematology and serum chemistry, blood and CSF cultures, endocrinology assessments, CSF
      analysis, and, pre- and post 131I-omburtamab performance testing. Performance testing will be
      performed at trial baseline, at week 26 and every 6 months during trial period.
    

Trial Arms

NameTypeDescriptionInterventions
131I-omburtamabExperimentalOne treatment cycle of 131I-omburtamab consists of 2 doses; 2mCi at week 1 and 50mCi at week 2). First cycle is initiated right after confirmation of eligibility at week 1. At week 6 the participant will be evaluated for safety and if eligible, receive a second cycle of 131I-omburtamab. Secondary efficacy endpoints will be evaluated at week 26 and primary efficacy endpoint will be evaluated at week 156.
  • 131I-omburtamab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have a histologically confirmed diagnosis of neuroblastoma with relapse
             in the central nervous system or in the meninges (leptomeningeal).

          -  Patients must be between the ages of birth and 18 years at the time of screening.

          -  Patients must have a life expectancy of at least 3 months.

        Exclusion Criteria:

          -  Patients with primary neuroblastoma in central nervous system.

          -  Patients must not have an uncontrolled life-threatening infection.

          -  Patients must not have received cranial or spinal irradiation less than 3 weeks prior
             to first dose of 131I-omburtamab in this trial.

          -  Patients must not have received systemic chemotherapy (corticosteroids not included)
             less than 3 weeks prior to enrollment in this trial.

          -  Patients must not have severe major non-hematologic organ toxicity; specifically, any
             renal, cardiac, hepatic, pulmonary, and gastrointestinal system toxicity must fall
             below Grade 3 prior to enrollment in this trial. Patients with stable neurological
             deficits (due to brain tumor) are not excluded. Patients with Grade 3 or lower hearing
             loss are not excluded.
      
Maximum Eligible Age:18 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival rate
Time Frame:3 years
Safety Issue:
Description:Overall survival rate at 3 years after the first treatment dose of 131I-omburtamab.

Secondary Outcome Measures

Measure:Overall survival
Time Frame:3 years
Safety Issue:
Description:Overall survival at 3 years after the first treatment dose of 131I-omburtamab.
Measure:Objective response rate (ORR)
Time Frame:3 years
Safety Issue:
Description:ORR is defined and assessed as a combination of partial response and complete response as defined by the RANO criteria and CSF cytology.
Measure:Objective response rate (ORR)
Time Frame:3 years
Safety Issue:
Description:ORR according to CSF cytology. ORR is defined and assessed as a combination of partial response and complete response.
Measure:CNS progression free survival (PFS)
Time Frame:6 month
Safety Issue:
Description:CNS PFS will be assessed at 6 months after the first treatment dose of 131I-omburtamab by comparing baseline radiological scans by MRI to radiological scans conducted 26 weeks after 131I-omburtamab treatment.
Measure:Dosimetry of 131I-omburtamab
Time Frame:2 weeks
Safety Issue:
Description:Whole-body, organ, blood, and CSF radiation dosimetry.
Measure:Assessment of peak plasma concentration (Cmax) of 131I-omburtamab
Time Frame:Baseline, 30 minutes, 1 hour, 4 hour, 1, 2, 3 and 7 days
Safety Issue:
Description:Cmax will be calculated and summarized with descriptive statistics.
Measure:Assessment of residence time of 131I-omburtamab
Time Frame:Baseline, 30 minutes, 1 hour, 4 hour, 1, 2, 3 and 7 days.
Safety Issue:
Description:Residence time will be calculated and summarized with descriptive statistics.
Measure:Assessment of elimination half-life of 131I-omburtamab
Time Frame:Baseline, 30 minutes, 1 hour, 4 hour, 1, 2, 3 and 7 days.
Safety Issue:
Description:Elimination half-life will be calculated and summarized with descriptive statistics.
Measure:Safety of 131I-omburtamab
Time Frame:3 years
Safety Issue:
Description:The frequency, type, and duration of treatment-emergent severe adverse events and serious adverse events, including clinically significant laboratory abnormalities. All adverse events will be graded according to CTCAE, version 4.0.
Measure:Performance assessment
Time Frame:3 years
Safety Issue:
Description:Performance assessment to monitor gross changes in neurological function is performed at week 26 and subsequently every 6 months during trial period using Lansky (< 16 years) and Karnofsky (≥ 16 years).

Details

Phase:Phase 2/Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Y-mAbs Therapeutics

Trial Keywords

  • Radioimmunotherapy
  • Neuroblastoma
  • CNS Metastases
  • Leptomeningeal Metastases
  • Pediatric

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