Medulloblastoma, Childhood
Conditions
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.
Interventions
DRUG177Lu-DTPA-omburtamab
Biological, radiolabeled DPTA-omburtamab
Sponsors
Y-mAbs Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
3 Years to 19 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicities (DLTs) Part 1 | Days 1 through 35 in cycle 1 | Summary of DLTs in DLT evaluable subjects. |
Countries
Denmark, Netherlands, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 10 mCi 177Lu-DTPA-omburtamab Intracerebroventricular administration of 10 mCi 177Lu-DTPA-omburtamab for up to two cycles (Part 1).
177Lu-DTPA-omburtamab: Biological, radiolabeled DPTA-omburtamab | 1 |
| 25 mCi 177Lu-DTPA-omburtamab Intracerebroventricular administration of 25 mCi 177Lu-DTPA-omburtamab for up to two cycles (Part 1).
177Lu-DTPA-omburtamab: Biological, radiolabeled DPTA-omburtamab | 1 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Trial terminated by sponsor | 1 | 1 |
Baseline characteristics
| Characteristic | 10 mCi 177Lu-DTPA-omburtamab | 25 mCi 177Lu-DTPA-omburtamab | Total |
|---|---|---|---|
| Age, Continuous | 15 years | 8 years | 11.5 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants | 2 Participants |
| Region of Enrollment Denmark | 0 participants | 1 participants | 1 participants |
| Region of Enrollment United States | 1 participants | 0 participants | 1 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 0 / 1 | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 | 0 / 1 |
Outcome results
Primary
Dose Limiting Toxicities (DLTs) Part 1
Summary of DLTs in DLT evaluable subjects.
Time frame: Days 1 through 35 in cycle 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 10 mCi 177Lu-DTPA-omburtamab | Dose Limiting Toxicities (DLTs) Part 1 | 0 Participants |
| 25 mCi 177Lu-DTPA-omburtamab | Dose Limiting Toxicities (DLTs) Part 1 | 1 Participants |