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

Primary Purpose

Medulloblastoma, Childhood

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
177Lu-DTPA-omburtamab
Sponsored by
Y-mAbs Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Medulloblastoma, Childhood

Eligibility Criteria

3 Years - 19 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically confirmed diagnosis of medulloblastoma.
  • SHH, Group 3, or Group 4 according to World Health Organisation (WHO) 2016 classification.
  • 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.
  • Have refractory disease, focal or multifocal recurrent disease, or pure leptomeningeal disease. Cytological or radiographic remission is allowed; however, not simultaneously.
  • 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 > 15 mm in the smallest diameter.
  • Ventriculoperitoneal shunts without programmable valves. Ventriculo-atrial or ventriculo-pleural shunts.
  • Grade 4 nervous system disorder. Stable neurological deficits (due to brain tumor or surgery) 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.
  • Other significant disease or condition that in the investigator's opinion would exclude the patient from the trial.

Sites / Locations

  • Mayo Clinic
  • Memorial Sloan Kettering Cancer Center
  • Doernbecher Children's Hospital
  • M.D. Anderson Cancer Center
  • Rigshospitalet, Børneonkologisk afsnit
  • Princess Máxima
  • Hospital Universitari Vall d'Hebron
  • Hospital Sant Joan de Deu de Barcelona
  • The Royal Marsden Hospital
  • Great North Children's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

177Lu-DTPA-omburtamab

Arm Description

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

Outcomes

Primary Outcome Measures

Dose Limiting Toxicities (DLTs) Part 1
Summary of DLTs in DLT evaluable subjects.

Secondary Outcome Measures

Full Information

First Posted
November 11, 2019
Last Updated
September 11, 2023
Sponsor
Y-mAbs Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT04167618
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Terminated
Why Stopped
Business priorities
Study Start Date
September 30, 2021 (Actual)
Primary Completion Date
August 11, 2022 (Actual)
Study Completion Date
August 11, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Y-mAbs Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Medulloblastoma, Childhood

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
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)
Allocation
N/A
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
177Lu-DTPA-omburtamab
Arm Type
Experimental
Arm Description
Intracerebroventricular administration of 177Lu-DTPA-omburtamab for up to two cycles (Part 1) and up to five cycles (Part 2).
Intervention Type
Drug
Intervention Name(s)
177Lu-DTPA-omburtamab
Intervention Description
Biological, radiolabeled DPTA-omburtamab
Primary Outcome Measure Information:
Title
Dose Limiting Toxicities (DLTs) Part 1
Description
Summary of DLTs in DLT evaluable subjects.
Time Frame
Days 1 through 35 in cycle 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed diagnosis of medulloblastoma. SHH, Group 3, or Group 4 according to World Health Organisation (WHO) 2016 classification. 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. Have refractory disease, focal or multifocal recurrent disease, or pure leptomeningeal disease. Cytological or radiographic remission is allowed; however, not simultaneously. 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 > 15 mm in the smallest diameter. Ventriculoperitoneal shunts without programmable valves. Ventriculo-atrial or ventriculo-pleural shunts. Grade 4 nervous system disorder. Stable neurological deficits (due to brain tumor or surgery) 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. Other significant disease or condition that in the investigator's opinion would exclude the patient from the trial.
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Doernbecher Children's Hospital
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
M.D. Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Rigshospitalet, Børneonkologisk afsnit
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Princess Máxima
City
Utrecht
ZIP/Postal Code
3584CS
Country
Netherlands
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Sant Joan de Deu de Barcelona
City
Barcelona
ZIP/Postal Code
08950
Country
Spain
Facility Name
The Royal Marsden Hospital
City
London
Country
United Kingdom
Facility Name
Great North Children's Hospital
City
Newcastle
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

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