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

NCT04167618 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: 301
• Study Type: interventional
• Target: 2
• Locations: 5 countries
• Sites: 10

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.

Conditions

Medulloblastoma, Childhood

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicities (DLTs) Part 1

  Summary of DLTs in DLT evaluable subjects.

  Days 1 through 35 in cycle 1

Study Arms (1)

177Lu-DTPA-omburtamab

EXPERIMENTAL

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

Drug: 177Lu-DTPA-omburtamab

Interventions

177Lu-DTPA-omburtamab DRUG

Biological, radiolabeled DPTA-omburtamab

177Lu-DTPA-omburtamab

Eligibility Criteria

• Age: 3 Years - 19 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Y-mAbs Therapeutics: lead

Study Sites (10)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Doernbecher Children's Hospital

Portland, Oregon, 97239, United States

Location

M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Rigshospitalet, Børneonkologisk afsnit

Copenhagen, 2100, Denmark

Location

Princess Máxima

Utrecht, 3584CS, Netherlands

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Sant Joan de Deu de Barcelona

Barcelona, 08950, Spain

Location

The Royal Marsden Hospital

London, United Kingdom

Location

Great North Children's Hospital

Newcastle, United Kingdom

Location

MeSH Terms

Conditions

Medulloblastoma

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors, Primitive; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Limitations and Caveats

The trial was terminated after 2 subjects due to a business strategy decision. At this point the maximum tolerated dose was not established.

Results Point of Contact

• Title: Joris Wilms
• Organization: Y-mAbs Therapeutics

clinicaltrials@ymabs.com

+4570261414

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 11, 2019
• First Posted: November 19, 2019
• Study Start: September 30, 2021
• Primary Completion: August 11, 2022
• Study Completion: August 11, 2022
• Last Updated: October 6, 2023
• Results First Posted: October 6, 2023

Record last verified: 2023-09

Locations

NL (1); US (4); GB (2); ES (2); DK (1)