Description:
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.
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
301
- NCT ID:
NCT04167618
Conditions
- Medulloblastoma, Childhood
Interventions
| Drug | Synonyms | Arms |
|---|
| 177Lu-DTPA-omburtamab | | 177Lu-DTPA-omburtamab |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| 177Lu-DTPA-omburtamab | Experimental | Intracerebroventricular administration of 177Lu-DTPA-omburtamab for up to two cycles (Part 1) and up to five cycles (Part 2). | |
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed diagnosis of medulloblastoma.
- Available molecular classification according to World Health Organisation (WHO) 2016
classification, as follows:
- WNT, SHH, Group 3, or Group 4 for patients enrolled to Part 1.
- SHH, Group 3, or Group 4 for patients enrolled to Part 2.
- 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.
- Be in cytological or radiographic remission, have residual disease, multifocal
recurrent disease, or pure leptomeningeal disease.
- 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 > 5 mm in the smallest diameter.
- Ventriculoperitoneal shunts without programmable valves. Ventriculo-atrial or
ventriculo-pleural shunts.
- Grade 4 neurotoxicity. Grade 3 or lower stable neurological deficits (due to brain
tumor) 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.
| Maximum Eligible Age: | 19 Years |
| Minimum Eligible Age: | 3 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Incidence of adverse events (AEs) and serious adverse events (SAEs) |
| Time Frame: | 1 year |
| Safety Issue: | |
| Description: | 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 |
Secondary Outcome Measures
| Measure: | Analysis of lutetium-177 activity in blood |
| Time Frame: | 2 weeks |
| Safety Issue: | |
| Description: | The time for maximum absorbed radiation dose |
| Measure: | Analysis of lutetium-177 activity in blood |
| Time Frame: | 2 weeks |
| Safety Issue: | |
| Description: | Elimination half-life of radioactivity |
| Measure: | Absorbed radiation dose of lutetium-177 in blood and cerebrospinal fluid (CSF) |
| Time Frame: | 2 weeks |
| Safety Issue: | |
| Description: | Time-activity curves of radioactivity measurements in blood and CSF will be modeled to deliver absorbed doses in blood and CSF |
| Measure: | Dosimetry analysis of lutetium-177 |
| Time Frame: | 2 weeks |
| Safety Issue: | |
| Description: | Whole-body dosimetry by gamma camera scans and single-photon emission computed tomography (SPECT) |
| Measure: | Maximum Plasma Concentration [Cmax] in CSF |
| Time Frame: | 7 weeks |
| Safety Issue: | |
| Description: | Concentration of 177Lu-DTPA-omburtamab in CSF |
| Measure: | Maximum Plasma Concentration [Cmax] in serum |
| Time Frame: | 7 weeks |
| Safety Issue: | |
| Description: | Concentration of 177Lu-DTPA-omburtamab in serum |
| Measure: | Elimination Half Life in CSF |
| Time Frame: | 7 weeks |
| Safety Issue: | |
| Description: | Concentration of 177Lu-DTPA-omburtamab in CSF |
| Measure: | Elimination Half Life in serum |
| Time Frame: | 7 weeks |
| Safety Issue: | |
| Description: | Concentration of 177Lu-DTPA-omburtamab in serum |
| Measure: | Response |
| Time Frame: | 2 years |
| Safety Issue: | |
| Description: | 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 |
| Measure: | Investigator-assessed duration of response (DoR) |
| Time Frame: | 2 years |
| Safety Issue: | |
| Description: | DoR is defined as the time from response (CR or PR) to progression |
| Measure: | Progression Free Survival (PFS) |
| Time Frame: | 2 years |
| Safety Issue: | |
| Description: | PFS is defined as the time from the first treatment to date of progression or death from any cause, whichever comes first |
| Measure: | Overall Survival (OS) |
| Time Frame: | 2 years |
| Safety Issue: | |
| Description: | OS is defined as the time from first treatment until death |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Y-mAbs Therapeutics |
Last Updated
September 1, 2021
