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

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: NCT04167618
Recruitment Status : Not yet recruiting
First Posted : November 19, 2019
Last Update Posted : April 17, 2020
Sponsor:
Information provided by (Responsible Party):
Y-mAbs Therapeutics

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Medulloblastoma, Childhood Drug: 177Lu-DTPA-omburtamab Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Patients will receive up to two cycles in Part 1 and up to five cycles in Part 2 of intracerebroventricular 177Lu-DTPA-omburtamab. Safety and efficacy will be investigated during treatment and follow-up period.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : October 15, 2020
Estimated Primary Completion Date : October 15, 2024
Estimated Study Completion Date : October 15, 2024


Arm Intervention/treatment
Experimental: 177Lu-DTPA-omburtamab
Intracerebroventricular administration of 177Lu-DTPA-omburtamab for up to two cycles (Part 1) and up to five cycles (Part 2).
Drug: 177Lu-DTPA-omburtamab
Biological, radiolabeled DPTA-omburtamab




Primary Outcome Measures :
  1. Incidence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: 1 year ]
    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

  2. Incidence of AEs and SAEs [ Time Frame: 2 years ]
    In Part 2, safety will be evaluated by the incidence of AEs and SAEs graded according to CTCAE version 5.0, at the RP2D defined in Part 1


Secondary Outcome Measures :
  1. Analysis of lutetium-177 activity in blood [ Time Frame: 2 weeks ]
    The time for maximum absorbed radiation dose

  2. Analysis of lutetium-177 activity in blood [ Time Frame: 2 weeks ]
    Elimination half-life of radioactivity

  3. Absorbed radiation dose of lutetium-177 in blood and cerebrospinal fluid (CSF) [ Time Frame: 2 weeks ]
    Time-activity curves of radioactivity measurements in blood and CSF will be modeled to deliver absorbed doses in blood and CSF

  4. Dosimetry analysis of lutetium-177 [ Time Frame: 2 weeks ]
    Whole-body dosimetry by gamma camera scans and single-photon emission computed tomography (SPECT)

  5. Maximum Plasma Concentration [Cmax] in CSF [ Time Frame: 7 weeks ]
    Concentration of 177Lu-DTPA-omburtamab in CSF

  6. Maximum Plasma Concentration [Cmax] in serum [ Time Frame: 7 weeks ]
    Concentration of 177Lu-DTPA-omburtamab in serum

  7. Elimination Half Life in CSF [ Time Frame: 7 weeks ]
    Concentration of 177Lu-DTPA-omburtamab in CSF

  8. Elimination Half Life in serum [ Time Frame: 7 weeks ]
    Concentration of 177Lu-DTPA-omburtamab in serum

  9. Response [ Time Frame: 2 years ]
    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

  10. Investigator-assessed duration of response (DoR) [ Time Frame: 2 years ]
    DoR is defined as the time from response (CR or PR) to progression

  11. Progression Free Survival (PFS) [ Time Frame: 2 years ]
    PFS is defined as the time from the first treatment to date of progression or death from any cause, whichever comes first

  12. Overall Survival (OS) [ Time Frame: 2 years ]
    OS is defined as the time from first treatment until death



Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 19 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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): NCT04167618


Contacts
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Contact: Joris Wilms +4570261414 clinicaltrials@ymabs.com

Sponsors and Collaborators
Y-mAbs Therapeutics
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Responsible Party: Y-mAbs Therapeutics
ClinicalTrials.gov Identifier: NCT04167618    
Other Study ID Numbers: 301
First Posted: November 19, 2019    Key Record Dates
Last Update Posted: April 17, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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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Medulloblastoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neuroectodermal Tumors, Primitive
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue