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

Phase 1

Terminated

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.

Recruitment & 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.

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Dose Limiting Toxicities (DLTs) Part 1	Days 1 through 35 in cycle 1	Summary of DLTs in DLT evaluable subjects.

Secondary Outcome Measures

Name	Time	Method

Locations (10): Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
Memorial Sloan Kettering Cancer Center
🇺🇸
New York, New York, United States
Doernbecher Children's Hospital
🇺🇸
Portland, Oregon, United States
M.D. Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Rigshospitalet, Børneonkologisk afsnit
🇩🇰
Copenhagen, Denmark
Princess Máxima
🇳🇱
Utrecht, Netherlands
Hospital Universitari Vall d'Hebron
🇪🇸
Barcelona, Spain
Hospital Sant Joan de Deu de Barcelona
🇪🇸
Barcelona, Spain
The Royal Marsden Hospital
🇬🇧
London, United Kingdom
Great North Children's Hospital
🇬🇧
Newcastle, United Kingdom
Mayo Clinic
🇺🇸Rochester, Minnesota, United States