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

• ClinicalTrials.gov Identifier: NCT04167618
• Recruitment Status: Terminated
• First Posted: November 19, 2019
• Last Update Posted: August 18, 2022
• Sponsor: Y-mAbs Therapeutics
• Information provided by (Responsible Party): Y-mAbs Therapeutics

Tracking Information

• First Submitted Date: November 11, 2019
• First Posted Date: November 19, 2019
• Last Update Posted Date: August 18, 2022
• Actual Study Start Date: September 30, 2021
• Actual Primary Completion Date: August 11, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 14, 2019)

• Incidence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: 1 year ]
  Safety will be evaluated by the incidence of AEs and SAEs graded according to CTCAE version 5.0. The maximum tolerated dose and the recommended phase 2 dose (RP2D) will be determined in Part 1
• Incidence of AEs and SAEs [ Time Frame: 2 years ]
  In Part 2, safety will be evaluated by the incidence of AEs and SAEs graded according to CTCAE version 5.0, at the RP2D defined in Part 1

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 15, 2020)

• Analysis of lutetium-177 activity in blood [ Time Frame: 2 weeks ]
  The time for maximum absorbed radiation dose
• Analysis of lutetium-177 activity in blood [ Time Frame: 2 weeks ]
  Elimination half-life of radioactivity
• Absorbed radiation dose of lutetium-177 in blood and cerebrospinal fluid (CSF) [ Time Frame: 2 weeks ]
  Time-activity curves of radioactivity measurements in blood and CSF will be modeled to deliver absorbed doses in blood and CSF
• Dosimetry analysis of lutetium-177 [ Time Frame: 2 weeks ]
  Whole-body dosimetry by gamma camera scans and single-photon emission computed tomography (SPECT)
• Maximum Plasma Concentration [Cmax] in CSF [ Time Frame: 7 weeks ]
  Concentration of 177Lu-DTPA-omburtamab in CSF
• Maximum Plasma Concentration [Cmax] in serum [ Time Frame: 7 weeks ]
  Concentration of 177Lu-DTPA-omburtamab in serum
• Elimination Half Life in CSF [ Time Frame: 7 weeks ]
  Concentration of 177Lu-DTPA-omburtamab in CSF
• Elimination Half Life in serum [ Time Frame: 7 weeks ]
  Concentration of 177Lu-DTPA-omburtamab in serum
• Response [ Time Frame: 2 years ]
  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
• Investigator-assessed duration of response (DoR) [ Time Frame: 2 years ]
  DoR is defined as the time from response (CR or PR) to progression
• Progression Free Survival (PFS) [ Time Frame: 2 years ]
  PFS is defined as the time from the first treatment to date of progression or death from any cause, whichever comes first
• Overall Survival (OS) [ Time Frame: 2 years ]
  OS is defined as the time from first treatment until death

Original Secondary Outcome Measures (submitted: November 14, 2019)

• Pharmacokinetic analysis of lutetium-177 in blood [ Time Frame: 2 weeks ]
  The time for maximum absorbed radiation dose
• Pharmacokinetic analysis of lutetium-177 in blood [ Time Frame: 2 weeks ]
  Elimination half-life of radioactivity
• Absorbed radiation dose of lutetium-177 in blood and cerebrospinal fluid (CSF) [ Time Frame: 2 weeks ]
  Time-activity curves of radioactivity measurements in blood and CSF will be modeled to deliver absorbed doses in blood and CSF
• Dosimetry analysis of lutetium-177 [ Time Frame: 2 weeks ]
  Whole-body dosimetry by gamma camera scans and single-photon emission computed tomography (SPECT)
• Objective Response Rate (ORR) [ Time Frame: 1 year (Part 1); 2 years (Part 2) ]
  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) and cerebrospinal fluid (CSF) cytology
• Progression Free Survival (PFS) [ Time Frame: 1 year (Part 1); 2 years (Part 2) ]
  PFS is defined as the time from the first treatment to date of progression or death from any cause, whichever comes first
• Overall Survival (OS) [ Time Frame: 2 years ]
  OS is defined as the time from first treatment until death from any cause

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 177Lu-DTPA-Omburtamab Radioimmunotherapy for Recurrent or Refractory Medulloblastoma
• Official Title: 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
• 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 Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

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.

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Medulloblastoma, Childhood

Intervention

Drug: 177Lu-DTPA-omburtamab

Biological, radiolabeled DPTA-omburtamab

Study Arms

Experimental: 177Lu-DTPA-omburtamab

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

Intervention: Drug: 177Lu-DTPA-omburtamab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: August 15, 2022): 2
• Original Estimated Enrollment (submitted: November 14, 2019): 40
• Actual Study Completion Date: August 11, 2022
• Actual Primary Completion Date: August 11, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 3 Years to 19 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Denmark, Netherlands, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04167618
• Other Study ID Numbers: 301
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Y-mAbs Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Y-mAbs Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Y-mAbs Therapeutics
• Verification Date: August 2022