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

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

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.

Study Overview

• Status: Terminated
• Conditions: Medulloblastoma, Childhood
• Intervention / Treatment: Drug: 177Lu-DTPA-omburtamab

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 Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet, Børneonkologisk afsnit
• Netherlands
  • Utrecht, Netherlands, 3584CS
    • Princess Máxima
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebrón
  • Barcelona, Spain, 08950
    • Hospital Sant Joan de Déu de Barcelona
• United Kingdom
  • London, United Kingdom
    • The Royal Marsden hospital
  • Newcastle, United Kingdom
    • Great North Children's Hospital
• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Doernbecher Children's Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • M.D. Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 15 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 177Lu-DTPA-omburtamab; Intracerebroventricular administration of 177Lu-DTPA-omburtamab for up to two cycles (Part 1) and up to five cycles (Part 2).	Drug: 177Lu-DTPA-omburtamab; Biological, radiolabeled DPTA-omburtamab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicities (DLTs) Part 1	Summary of DLTs in DLT evaluable subjects.	Days 1 through 35 in cycle 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analysis of lutetium-177 activity in blood	The time for maximum absorbed radiation dose	2 weeks
Analysis of lutetium-177 activity in blood	Elimination half-life of radioactivity	2 weeks
Absorbed radiation dose of lutetium-177 in blood and cerebrospinal fluid (CSF)	Time-activity curves of radioactivity measurements in blood and CSF will be modeled to deliver absorbed doses in blood and CSF	2 weeks
Dosimetry analysis of lutetium-177	Whole-body dosimetry by gamma camera scans and single-photon emission computed tomography (SPECT)	2 weeks
Maximum Plasma Concentration [Cmax] in CSF	Concentration of 177Lu-DTPA-omburtamab in CSF	7 weeks
Maximum Plasma Concentration [Cmax] in serum	Concentration of 177Lu-DTPA-omburtamab in serum	7 weeks
Elimination Half Life in CSF	Concentration of 177Lu-DTPA-omburtamab in CSF	7 weeks
Elimination Half Life in serum	Concentration of 177Lu-DTPA-omburtamab in serum	7 weeks
Response	Objective Response Rate (ORR) is defined as partial response (PR) or complete response (CR) and as defined by the Response Assessment in Pediatric Neuro Oncology (RAPNO) criteria (as determined from magnetic resonance imaging [MRI] assessments), neurological examination, and cerebrospinal fluid (CSF) cytology	2 years
Investigator-assessed duration of response (DoR)	DoR is defined as the time from response (CR or PR) to progression	2 years
Progression Free Survival (PFS)	PFS is defined as the time from the first treatment to date of progression or death from any cause, whichever comes first	2 years
Overall Survival (OS)	OS is defined as the time from first treatment until death	2 years

Collaborators and Investigators

• Sponsor: Y-mAbs Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2021
• Primary Completion (Actual): August 11, 2022
• Study Completion (Actual): August 11, 2022

Study Registration Dates

• First Submitted: November 11, 2019
• First Submitted That Met QC Criteria: November 14, 2019
• First Posted (Actual): November 19, 2019

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: September 11, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Medulloblastoma
• Other Study ID Numbers: 301 (Yasar Calıskan)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No