Medulloblastoma MedDRA version: 21.0 Level: PT Classification code 10066594 Term: Medulloblastoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10027107 Term: Medulloblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: 177Lu-DTPA-omburtamab
Product Code: 177Lu-DTPA-murine 8H9
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Omburtamab
CAS Number: 1895083-75-6
Current Sponsor code: 177Lu
Sponsors
Y-mAbs Therapeutics Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must satisfy all of the following criteria at the Screening Visit, unless otherwise stated: 1. Histologically confirmed diagnosis of medulloblastoma. 2. SHH, Group 3, or Group 4 according to World Health Organization 2016 classification. 3. Recurrent or refractory to frontline therapy, defined as: a. For Part 1 only: Recurrent (maximum of 2 recurrences) or refractory to frontline therapy. Prior frontline or second-line therapy may involve surgery, craniospinal irradiation, stereotactic radiosurgery, and multi-agent chemotherapy regimens. b. For Part 2 only: Recurrent (maximum of 1 recurrence) or refractory to frontline therapy. Patients with recurrent disease must have received second-line chemotherapy for progressive disease. Prior frontline or second-line therapy may involve surgery, craniospinal irradiation, stereotactic radiosurgery, and multiagent chemotherapy regimens. 4. Have refractory disease, focal or multifocal recurrent disease, or pure leptomeningeal disease. Cytological or radiographic remission is allowed; however, not simultaneously. 5. Performance status score of 50 to 100, both inclusive, on the Lansky [60 mL/min/1.73 m2, calculated by the 2009 revised Bedside Schwartz Equation. 11. Written informed consent from legal guardian(s) and/or child obtained in accordance with local regulations. Pediatric patients must provide assent as required by local regulations. Are the trial subjects under 18? yes Number of subjects for this age range: 49 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 2 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Obstructive or symptomatic communicating hydrocephalus as determined by Ommaya patency/CSF flow assessment. 2. Any tumor lesion measuring >15 mm in the smallest diameter. 3. Ventriculoperitoneal (VP) shunts without programmable valves. Ventriculo-atrial or ventriculo-pleural shunts. 4. Grade 4 nervous system disorder. Stable neurological deficits due to brain tumor or surgery and hearing loss are allowed. 5. Uncontrolled life-threatening infection. 6. Received radiation therapy (focal or cranio-spinal irradiation), systemic or intrathecal cytotoxic chemotherapy, or immunotherapy (including monoclonal antibodies; corticosteroids not included) less than 3 weeks prior to the Dosimetry Dose (or until recovery from clinically significant adverse events). Received nitrosoureas less than 6 weeks prior to the Dosimetry Dose. 7. Received any prior anti-B7-H3 treatment. 8. Non-hematologic organ toxicity Grade 3 or above; specifically, any renal, cardiac, hepatic, pulmonary, and gastrointestinal system toxicity. 9. Other significant disease or condition that in the investigator's opinion would exclude the patient from the trial. 10. Females of childbearing potential who are pregnant, breast feeding, intend to become pregnant, or are not using highly effectiven contraceptive methods or males who are not using highly effective contraceptive methods.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: The secondary objectives of Part 1 (dose-escalation phase) are: •to evaluate the absorbed radiation doses to CSF and blood of 177Lu- DTPA-omburtamab after intracerebroventricular administration •to evaluate organ dosimetry of 177Lu-DTPA-omburtamab •to evaluate the PK profile of 177Lu-DTPA-omburtamab The secondary objectives of Part 2 (cohort-expansion phase) are: •to evaluate the PK profile of 177Lu-DTPA-omburtamab •to evaluate the investigator-assessed response •to evaluate the investigator-assessed DoR •to evaluate PFS •to evaluate overall survival OS.;Main Objective: The primary objective of Part 1 (dose-escalation phase) of this trial is to explore the tolerability of up to 2 cycles of intracerebroventricular 177Lu-DTPA-omburtamab treatment in pediatric and adolescent patients with recurrent or refractory medulloblastoma. The MTD and/or the RP2D for Part 2 will be determined. The primary objective of Part 2 (cohort-expansion phase) of this trial is to establish a safety profile of repeated dosing of 177Lu-DTPA-omburtamab in pediatric and adolescent patients with recurrent or refractory medulloblastoma. ;Primary end point(s): The primary endpoint of Part 1 is number of DLTs (dose-limiting toxicity). The primary endpoint of Part 2 is number and severity of TEAEs (treatment-emergent adverse event).;Timepoint(s) of evaluation of this end point: Part 1: At the end of 5 week Cycle. Part 2: Analysis with occur after database lock | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1 •Lutetium-177 activity in blood and CSF including derivation of best-fit uptake and/or clearance parameters (maximum count, elimination half life) of time-activity curves and residence times (i.e., cumulated activity in µCi·h/g). •Whole-body, organ, blood, and CSF radiation dosimetry. •PK profile of 177Lu-DTPA-omburtamab in serum and CSF. Part 2 •PK profile of 177Lu-DTPA-omburtamab in blood and CSF. •Response, as defined by the RAPNO criteria (as determined from MRI assessments, neurological examination, and CSF cytology). •ORR, calculated as the proportion of all evaluable patients achieving a response (PR or CR) as best overall response at end of Cycle 1 and Cycle 3, EOT Visit, and at each Follow-up Visit. •Investigator-assessed DoR, defined as the time from first response (CR or PR) to progression. •PFS, defined as the time from first treatment to date of leptomeningeal progression or death from any cause, whichever comes first. •OS defined as the time from first treatment to date of death;Timepoint(s) of evaluation of this end point: Part 1: at the EOT Visit Part 2: at end of Cycle 1 and Cycle 3, EOT Visit, then 26, 39, and 52 weeks post first dose, followed by 78 and 104 weeks post first dose of 177Lu-DTPA omburtamab. | — |
Countries
Denmark, United Kingdom, United States
Contacts
Public ContactGRS associate
Labcorp Clinical Development Limited
Outcome results
None listed