Clinical trial NCT04167618: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Medulloblastoma, Childhood
Lead sponsor: Y-mAbs Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-11-19
Enrollment: 2
Sex: ALL
Minimum age (years): 3
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Dose Limiting Toxicities (DLTs) Part 1
timeFrame: Days 1 through 35 in cycle 1
Secondary outcomes:
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Portland
country: United States
facility: Doernbecher Children's Hospital
state: Oregon
city: Houston
country: United States
facility: M.D. Anderson Cancer Center
state: Texas
city: Copenhagen
country: Denmark
facility: Rigshospitalet, Børneonkologisk afsnit
city: Utrecht
country: Netherlands
facility: Princess Máxima
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Deu de Barcelona
city: London
country: United Kingdom
facility: The Royal Marsden Hospital
city: Newcastle
country: United Kingdom
facility: Great North Children's Hospital
Study officials:
References: