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

Medulloblastoma, Childhood Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT04167618
• Other study ID #: 301
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: September 30, 2021
• Est. completion date: August 11, 2022

Study information

• Verified date: September 2023
• Source: Y-mAbs Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: August 11, 2022
• Est. primary completion date: August 11, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 19 Years

Eligibility

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.

Related Conditions & MeSH terms

• Medulloblastoma
• Medulloblastoma, Childhood

Intervention

Drug:
• 177Lu-DTPA-omburtamab
Biological, radiolabeled DPTA-omburtamab

Locations

Country	Name	City	State
Denmark	Rigshospitalet, Børneonkologisk afsnit	Copenhagen
Netherlands	Princess Máxima	Utrecht
Spain	Hospital Sant Joan de Deu de Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
United Kingdom	The Royal Marsden Hospital	London
United Kingdom	Great North Children's Hospital	Newcastle
United States	M.D. Anderson Cancer Center	Houston	Texas
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Doernbecher Children's Hospital	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Y-mAbs Therapeutics

Countries where clinical trial is conducted

United States,  Denmark,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicities (DLTs) Part 1	Summary of DLTs in DLT evaluable subjects.	Days 1 through 35 in cycle 1