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

Phase 1

Terminated

• Conditions: Medulloblastoma, Childhood
• Interventions: Drug: 177Lu-DTPA-omburtamab

• Registration Number: NCT04167618
• Lead Sponsor: 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.

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.

Study Timeline

• Study First Submitted: 2019-11-11
• Study First Submitted QC: 2019-11-14
• Study First Posted: 2019-11-19
• Study Start: 2021-09-30
• Primary Completion: 2022-08-11
• Study Completion: 2022-08-11
• Status Verified: 2023-09
• Results First Submitted: 2023-09-11
• Results First Submitted QC: 2023-09-11
• Last Update Submitted: 2023-09-11
• Results First Posted: 2023-10-06
• Last Update Posted: 2023-10-06

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

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.

Trial Locations

Locations (10)

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Doernbecher Children's Hospital; 🇺🇸 Portland, Oregon, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Rigshospitalet, Børneonkologisk afsnit; 🇩🇰 Copenhagen, Denmark

M.D. Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Princess Máxima; 🇳🇱 Utrecht, Netherlands

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital Sant Joan de Deu de Barcelona; 🇪🇸 Barcelona, Spain

Great North Children's Hospital; 🇬🇧 Newcastle, United Kingdom

The Royal Marsden Hospital; 🇬🇧 London, United Kingdom