A clinical study to determine the dose and assess safety and efficacy of radioimmuntherapy in patients with glioblastoma, where Lutetium 177 labelled 6A10 antibody Fab fragments are applied to the tumor resection cavity.

Phase 1

Recruiting

Conditions: Surgically treated high grade glioma after concomitant radiochemotherapy and adjuvant standard chemotherapy, with no or small stable tumor residue

Interventions: Drug: Lu-177 labeled 6A10-Fab-fragments

Registration Number: 2024-513638-39-00

Lead Sponsor: Universitaetsklinikum Muenster AöR

Brief 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.

Recruitment & Eligibility

Status: Ongoing, recruiting

Sex: Not specified

Target Recruitment: 15

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Lu-177-labeled-6A10Fab-fragments	Lu-177 labeled 6A10-Fab-fragments	The patient will receive a predetermined dose of Lu-177-labeled- 6A10Fab-fragments via the intracavitary reservoir. Patients will receive 3 RIT-cycles with an interval of 4 weeks. The total activity, adjusted to the volume of the RC, will be injected in 3 fractions with 50%, 25% and 25% of the total activity to achieve the desired boost to the 2 cm margin.

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose (MTD)	Through study completion, ca 1 ½ years	Determine maximum tolerated dose (MTD) and safety of adjuvant radio-immunotherapy (RIT) with Lu-177 labeled 6A10-Fab-fragments
Safety of the adjuvant radio-immunotherapy	Through study completion, ca 1 ½ years	Determining safety by assessing all new neurological, hematological and other AEs CTC grade 2 or higher

Secondary Outcome Measures

Name	Time	Method
Evaluation of pharmacokinetics of Lu-177 labeled 6A10 Fab fragments	After first application: 2 ,24 ,48, 72 hours post injection and on day 5-7. After second and third application.	Determining absorbed dose to the 2 cm shell of the resection cavity (based on a series of SPECT/CTs of the head 2 ,24 ,48, 72 hours post injection 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 2 ,24 ,48, 72 hours post injection and on day 5-7)
Progression-free survival (PFS)	Through study completion, an average of 18 months	Determining 24 weeks Progression-Free-Survival (PFS), defined from the day of inclusion

Trial Locations

Locations (4): Universitaetsklinikum Essen AöR
🇩🇪
Essen, Germany
Universitaet Muenster
🇩🇪
Muenster, Germany
University Hospital Cologne AöR
🇩🇪
Cologne, Germany
Universitaetsklinikum Wuerzburg AöR
🇩🇪
Wuerzburg, Germany
Universitaetsklinikum Essen AöR
🇩🇪Essen, Germany
Ken Herrmann
Site contact
00492017232032
ken.herrmann@uk-essen.de
Karsten Wrede
Site contact
00492017231210
Karsten.Wrede@uk-essen.de