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

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 49

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 [<16 years] or Karnofsky [=16 years] scales.
6. Aged 3 to 19 years, both inclusive, at the time of the first planned dose of trial treatment.
7. Life expectancy of at least 3 months, as judged by the investigator.
8. Acceptable hematological status prior to first dosing (hematological support is allowed if administered at least 1 week before administration of 177Lu-DTPA-omburtamab), defined as:
a. Hemoglobin =8 g/dL
b. White blood cell count =1000/µL.
c. Absolute neutrophil count =1000/µL
d. Platelet count =75 000/µL.
9. Acceptable liver function prior to first dosing, defined as:
a. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =5 × upper limit of normal (ULN)
b. Bilirubin =1.5 × ULN.
10. Acceptable kidney function prior to first dosing, defined as:
a. Estimated glomerular filtration rate (eGFR) >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

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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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