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

Y-mAbs Therapeutics

Status and phase

Terminated

Phase 2

Phase 1

Conditions

Medulloblastoma, Childhood

Treatments

Drug: 177Lu-DTPA-omburtamab

Study type

Interventional

Funder types

Industry

Identifiers

NCT04167618

301

Details and patient eligibility

About

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.

Full 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.

Enrollment

2 patients

Sex

All

Ages

3 to 19 years old

Volunteers

No 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.