Clinical Trials /

177Lu-DTPA-Omburtamab Radioimmunotherapy for Recurrent or Refractory Medulloblastoma

NCT04167618

Description:

Children and adolescents diagnosed with medullablastoma and with recurrent or refractory to frontline therapy will be treated with 177Lu-DTPA-omburtamab, which is a radioactive labelling of a murine monoclonal antibody targeting B7-H3.

Related Conditions:
  • Medulloblastoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 177Lu-DTPA-Omburtamab Radioimmunotherapy for Recurrent or Refractory Medulloblastoma
  • Official Title: A Phase I/II Dose-escalation and Expansion Cohort Trial of Intracerebroventricular Radioimmunotherapy Using 177Lu-DTPA-Omburtamab in Pediatric and Adolescent Patients With Recurrent or Refractory Medulloblastoma

Clinical Trial IDs

  • ORG STUDY ID: 301
  • NCT ID: NCT04167618

Conditions

  • Medulloblastoma, Childhood

Interventions

DrugSynonymsArms
177Lu-DTPA-omburtamab177Lu-DTPA-omburtamab

Purpose

Children and adolescents diagnosed with medullablastoma and with recurrent or refractory to frontline therapy will be treated with 177Lu-DTPA-omburtamab, which is a radioactive labelling of a murine monoclonal antibody targeting B7-H3.

Detailed Description

      Part 1 is a dose-escalation phase with a 3+3 sequential-group design in which patients will
      receive a dosimetry dose followed by maximum of two 5-week cycles of treatment doses of
      intracerebroventricular 177Lu-DTPA-omburtamab.

      Part 2 is a cohort-expansion phase in which patients will receive a maximum of five 5-week
      cycles of intracerebroventricular 177Lu-DTPA-omburtamab at the recommended dose determined in
      Part 1.

      End of treatment will take place within 5 weeks after the last cycle and thereafter the
      patients will be enter the follow-up period. The patients will be followed for up to 2 years
      after last dose.
    

Trial Arms

NameTypeDescriptionInterventions
177Lu-DTPA-omburtamabExperimentalIntracerebroventricular administration of 177Lu-DTPA-omburtamab for up to two cycles (Part 1) and up to five cycles (Part 2).
  • 177Lu-DTPA-omburtamab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of medulloblastoma.

          -  Available molecular classification according to World Health Organisation (WHO) 2016
             classification, as follows:

          -  WNT, SHH, Group 3, or Group 4 for patients enrolled to Part 1.

          -  SHH, Group 3, or Group 4 for patients enrolled to Part 2.

          -  Recurrent (maximum of 2 recurrences for Part 1 and 1 recurrence for Part 2) or
             refractory to frontline therapy. Prior frontline or second line therapy may involve
             surgery, craniospinal irradiation, stereotactic radiosurgery, and multi-agent
             chemotherapy regimens.

          -  Be in cytological or radiographic remission, have residual disease, multifocal
             recurrent disease, or pure leptomeningeal disease.

          -  Performance status score of 50 to 100 on Lansky (less than 16 years) or Karnofsky (16
             years or older) scales.

          -  Life expectancy of at least 3 months, as judged by the Investigator.

          -  Acceptable hematological status and liver and kidney function.

        Exclusion Criteria:

          -  Obstructive or symptomatic communicating hydrocephalus as determined by Ommaya
             patency/cerebrospinal fluid (CSF) flow study.

          -  Residual disease (nodular or linear) measuring > 5 mm in the smallest diameter.

          -  Ventriculoperitoneal shunts without programmable valves. Ventriculo-atrial or
             ventriculo-pleural shunts.

          -  Grade 4 neurotoxicity. Grade 3 or lower stable neurological deficits (due to brain
             tumor) or hearing loss are allowed.

          -  Uncontrolled life-threatening infection.

          -  Received radiation therapy less than 3 weeks prior to the screening visit.

          -  Received systemic or intrathecal cytotoxic chemotherapy or intrathecal immunotherapy
             (corticosteroids not included) less than 3 weeks prior to the screening visit.

          -  Received any prior anti-B7-H3 treatment.

          -  Non-hematologic organ toxicity Grade 3 or above; specifically, any renal, cardiac,
             hepatic, pulmonary, and gastrointestinal system toxicity.
      
Maximum Eligible Age:19 Years
Minimum Eligible Age:3 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events (AEs) and serious adverse events (SAEs)
Time Frame:1 year
Safety Issue:
Description:Safety will be evaluated by the incidence of AEs and SAEs graded according to CTCAE version 5.0. The maximum tolerated dose and the recommended phase 2 dose (RP2D) will be determined in Part 1

Secondary Outcome Measures

Measure:Analysis of lutetium-177 activity in blood
Time Frame:2 weeks
Safety Issue:
Description:The time for maximum absorbed radiation dose
Measure:Analysis of lutetium-177 activity in blood
Time Frame:2 weeks
Safety Issue:
Description:Elimination half-life of radioactivity
Measure:Absorbed radiation dose of lutetium-177 in blood and cerebrospinal fluid (CSF)
Time Frame:2 weeks
Safety Issue:
Description:Time-activity curves of radioactivity measurements in blood and CSF will be modeled to deliver absorbed doses in blood and CSF
Measure:Dosimetry analysis of lutetium-177
Time Frame:2 weeks
Safety Issue:
Description:Whole-body dosimetry by gamma camera scans and single-photon emission computed tomography (SPECT)
Measure:Maximum Plasma Concentration [Cmax] in CSF
Time Frame:7 weeks
Safety Issue:
Description:Concentration of 177Lu-DTPA-omburtamab in CSF
Measure:Maximum Plasma Concentration [Cmax] in serum
Time Frame:7 weeks
Safety Issue:
Description:Concentration of 177Lu-DTPA-omburtamab in serum
Measure:Elimination Half Life in CSF
Time Frame:7 weeks
Safety Issue:
Description:Concentration of 177Lu-DTPA-omburtamab in CSF
Measure:Elimination Half Life in serum
Time Frame:7 weeks
Safety Issue:
Description:Concentration of 177Lu-DTPA-omburtamab in serum
Measure:Response
Time Frame:2 years
Safety Issue:
Description:Objective Response Rate (ORR) is defined as partial response (PR) or complete response (CR) and as defined by the Response Assessment in Pediatric Neuro Oncology (RAPNO) criteria (as determined from magnetic resonance imaging [MRI] assessments), neurological examination, and cerebrospinal fluid (CSF) cytology
Measure:Investigator-assessed duration of response (DoR)
Time Frame:2 years
Safety Issue:
Description:DoR is defined as the time from response (CR or PR) to progression
Measure:Progression Free Survival (PFS)
Time Frame:2 years
Safety Issue:
Description:PFS is defined as the time from the first treatment to date of progression or death from any cause, whichever comes first
Measure:Overall Survival (OS)
Time Frame:2 years
Safety Issue:
Description:OS is defined as the time from first treatment until death

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Y-mAbs Therapeutics

Last Updated

October 2, 2020