NCT05533242

Radioimmunotherapy with Lu-177 Labeled 6A10 Fab-fragments in Patients with Glioblastoma After Standard Treatment

A Phase I Trial to Determine the Maximum Tolerated Dose and Patient-specific Dosimetry of Fractionated Intracavitary Radioimmunotherapy with Lu-177 Labeled 6A10 Fab-fragments in Patients with Glioblastoma After Standard Treatment

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sponsor: University Hospital Muenster · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

Locoregional, intracavitary radioimmunotherapy (iRIT) with a newly developed radioimmunoconjugate (Lu-177 labeled 6A10-Fab-fragments) will be used to prevent or postpone tumour recurrence in patients with GBM following standard therapy . Following study objectives will be analyzed: * Determining the Maximum Tolerated Dose (MTD) * Determining safety by assessing all new neurological, hematological and other AEs CTC grade 2 or higher * Determining absorbed dose to the 2 cm shell of the resection cavity (based on a series of SPECT/CTs of the head 2h,24h,48h, 72h p.i. and on day 5-7) * Determining absorbed dose values for the kidneys, the liver, the active marrow (based on a series of SPECT/CTs of the abdomen 2h,24h,48h, 72h p.i. and on day 5-7) * Determining 24 weeks Progression-Free-Survival (PFS), defined from the day of inclusion

Detailed description

In glioblastoma (GBM), tumour recurrence occurs adjacent to the initial tumor resection cavity in about 85% of cases (Albert et al., 1994; Bashir et al., 1988; Nestler et al., 2015). Therefore, local treatment concepts seem crucial for effective recurrence treatment strategies. We consider locoregional, intracavitary radioimmunotherapy (iRIT) to be a new therapeutic approach to delay or prevent the development of local tumour regrowth in GBM patients. By applying a radioimmunoconjugate (RIC) into the surgically created resection cavity (RC) the blood-brain barrier can effectively be by-passed, allowing the a deposit of high radiation doses locally while sparing sensitive organs like the bone marrow and the kidneys. LuCaFab (Lu-177 labeled 6A10- Fab-fragment) is a carbonic anhydrase XII-specific antibody Fab fragment developed by Helmholtz Munich, labeled with ITM's highly pure medical radioisotope, lutetium-177. (ITM IsotopeTechnologies Munich SE). Patients with GBM after standard therapy (surgery by radio-chemotherapy concomitant and adjuvant chemotherapy) Are eligible for the study. Patients will receive the calculated total doses of Lu-177-labeled 6A10-Fabs in three fractions with an interval of 4 weeks between injections, administered into the tumour cavity via an implanted reservoir. A patient specific dosing strategy will be applied and will depend on the individual RC volume. This investigator-initiated trial is sponsored by the University Hospital Münster, conducted in hospitals in Münster, Essen, Cologne, and Wuerzburg, and supported by ITM and Helmholtz Munich.

Conditions

• Glioblastom WHO Grade 4

Interventions

Type	Name	Description
DRUG	Lu-177 labeled 6A10-Fab-fragments	The antibody 6A10 is a specific CA12 Inhibitor, a highly specific glioma cell-associated enzyme; all tumor cells are CA12-positive, while its expression in normal brain is very low, and Lu-177 has a comparable β-emission, but a significantly low γ-Emission.

Timeline

• Start date: 2024-01-22
• Primary completion: 2026-04-01
• Completion: 2026-04-01
• First posted: 2022-09-08
• Last updated: 2025-03-30

Locations

7 sites across 1 country: Germany