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

• Sponsor: Y-mAbs Therapeutics (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT04167618
• Collaborator: (none)
• Enrollment: 2
• Locations: 10
• Arm: 1
• Actual Duration (Months): 10.3
• Patients Per Site: 0.2
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Medulloblastoma, Childhood	Drug: 177Lu-DTPA-omburtamab	Phase 1/Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• 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.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.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Sep 30, 2021
• Actual Primary Completion Date: Aug 11, 2022
• Actual Study Completion Date: Aug 11, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 177Lu-DTPA-omburtamab Intracerebroventricular administration of 177Lu-DTPA-omburtamab for up to two cycles (Part 1) and up to five cycles (Part 2).	Drug: 177Lu-DTPA-omburtamab; Biological, radiolabeled DPTA-omburtamab

Outcome Measures

Primary Outcome Measures

1. Incidence of adverse events (AEs) and serious adverse events (SAEs) [1 year]

   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

2. Incidence of AEs and SAEs [2 years]

   In Part 2, safety will be evaluated by the incidence of AEs and SAEs graded according to CTCAE version 5.0, at the RP2D defined in Part 1

Secondary Outcome Measures

1. Analysis of lutetium-177 activity in blood [2 weeks]

   The time for maximum absorbed radiation dose

2. Analysis of lutetium-177 activity in blood [2 weeks]

   Elimination half-life of radioactivity

3. Absorbed radiation dose of lutetium-177 in blood and cerebrospinal fluid (CSF) [2 weeks]

   Time-activity curves of radioactivity measurements in blood and CSF will be modeled to deliver absorbed doses in blood and CSF

4. Dosimetry analysis of lutetium-177 [2 weeks]

   Whole-body dosimetry by gamma camera scans and single-photon emission computed tomography (SPECT)

5. Maximum Plasma Concentration [Cmax] in CSF [7 weeks]

   Concentration of 177Lu-DTPA-omburtamab in CSF

6. Maximum Plasma Concentration [Cmax] in serum [7 weeks]

   Concentration of 177Lu-DTPA-omburtamab in serum

7. Elimination Half Life in CSF [7 weeks]

   Concentration of 177Lu-DTPA-omburtamab in CSF

8. Elimination Half Life in serum [7 weeks]

   Concentration of 177Lu-DTPA-omburtamab in serum

9. Response [2 years]

   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

10. Investigator-assessed duration of response (DoR) [2 years]

    DoR is defined as the time from response (CR or PR) to progression

11. Progression Free Survival (PFS) [2 years]

    PFS is defined as the time from the first treatment to date of progression or death from any cause, whichever comes first

12. Overall Survival (OS) [2 years]

    OS is defined as the time from first treatment until death

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years to 19 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905
2	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
3	Doernbecher Children's Hospital	Portland	Oregon	United States	97239
4	M.D. Anderson Cancer Center	Houston	Texas	United States	77030
5	Rigshospitalet, Børneonkologisk afsnit	Copenhagen		Denmark	2100
6	Princess Máxima	Utrecht		Netherlands	3584CS
7	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
8	Hospital Sant Joan de Deu de Barcelona	Barcelona		Spain	08950
9	The Royal Marsden Hospital	London		United Kingdom
10	Great North Children's Hospital	Newcastle		United Kingdom

Sponsors and Collaborators

• Y-mAbs Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Y-mAbs Therapeutics
• ClinicalTrials.gov Identifier: NCT04167618
• Other Study ID Numbers: 301
• First Posted: Nov 19, 2019
• Last Update Posted: Aug 18, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Medulloblastoma

Study Results

No Results Posted as of Aug 18, 2022