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

NCT05533242 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: UKM15_0027
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 7

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

Conditions

Glioblastom WHO Grade 4

Keywords

Carbonic anhydrase XII (CA XII); Intracavitary radioimmunotherapy; Fab fragment 6A10

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD)

  Determine maximum tolerated dose (MTD) and safety of adjuvant radio-immunotherapy (RIT) with Lu-177 labeled 6A10-Fab-fragments

  Through study completion, ca 1 ½ years

• Safety of the adjuvant radio-immunotherapy

  Determining safety by assessing all new neurological, hematological and other AEs CTC grade 2 or higher

  Through study completion, ca 1 ½ years

Secondary Outcomes (2)

• 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.

• Progression-free survival (PFS)

  Through study completion, an average of 18 months

Other Outcomes (1)

• Overall survival (OS)

  2 years from the day of inclusion

Study Arms (1)

Lu-177-labeled-6A10Fab-fragments

EXPERIMENTAL

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.

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

Interventions

Lu-177 labeled 6A10-Fab-fragments DRUG

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.

Lu-177-labeled-6A10Fab-fragments

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written patient consent after comprehensive information
• Age between 18 and 80 years
• Primary supratentorial high grade glioma after standard therapy (fluorescence-guided surgery, radio-chemotherapy, concomitant + adjuvant chemotherapy), with no or stable small tumor residue (residual contrast enhancement of up to 5cm3) at earliest 6 weeks after completion of radiotherapy
• Histological verification of glioblastoma and CA 12-expression of tumor cells confirmed
• Karnofsky-score ≥ 60
• Volume of resection cavity 2,5-25 cm3
• Male and female patients with reproductive potential must use an approved contraceptive method
• Pre-menopausal female patients with childbearing potential: a negative serum pregnancy test must be obtained prior to treatment start
• Adequate bone marrow reserve: white blood cell (WBC) count ≥3000/μl, granulocyte count \>1500/μl, platelets ≥100000/μl, hemoglobin ≥ 10 g/dl
• Adequate liver function: bilirubin \< 1.5 times above upper limit of normal range (ULN), alanine transaminase (ALT/SGPT) and aspartate transaminase (AST/SGOT) \< 3 times ULN. In the case of documented or suspected Gilbert's disease bilirubin \< 3 times ULN.
• Blood clotting: INR (=PT) and PTT within acceptable limits according to the investigator
• Adequate renal function: creatinine \< 3 times above ULN; eGFR \> (or equal) 60 ml/min

You may not qualify if:

• Patient unable to undergo imaging by CT, PET or contrast-enhanced MRI for whatever reason (i.e., pacemaker)
• Resection cavity with intraventricular access
• Significant leakage of radioactivity into CSF spaces or ventricles
• Other actively treated invasive malignancy
• Breastfeeding women
• Past medical history of diseases with poor prognosis, e.g., severe coronary heart disease, heart failure (NYHA III/IV), severe and poorly controlled diabetes, immune deficiency, residual deficits after stroke, severe mental retardation, pre-existing neurological diseases except those related to glioblastoma or other serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator)
• Any active infection (at the discretion of the investigator)
• Previous participation in a registered clinical trial with therapeutic intervention less than 6 weeks prior to enrolment (date of informed consent)
• Allergy against known constituents of study medication

Sponsors & Collaborators

• University Hospital Muenster: lead
• Isotope Technologies Munich (ITM) Oncologics: collaborator
• Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH): collaborator

Study Sites (7)

Klinik für Allgemeine Neurochirurgie des Universitätsklinikums Köln

Cologne, 50937, Germany

Location

Klinik für Nuklearmedizin des Universitätsklinikums Köln

Cologne, 50937, Germany

Location

Klinik für Neurochirurgie des Universitätsklinikums Essen

Essen, 45147, Germany

Location

Klinik für Nuklearmedizin, Strahlenklinik des Universitätsklinikums Essen

Essen, 45147, Germany

Location

Klinik für Nuklearmedizin der Universität Münster

Münster, 48149, Germany

Location

Universitätsklinikum Würzburg - Neurochirurgie

Würzburg, 97080, Germany

Location

Universitätsklinikum Würzburg - Nuklearmedizin

Würzburg, 97080, Germany

Location

Related Publications (6)

• Fiedler L, Kellner M, Gosewisch A, Oos R, Boning G, Lindner S, Albert N, Bartenstein P, Reulen HJ, Zeidler R, Gildehaus FJ. Evaluation of 177Lu[Lu]-CHX-A''-DTPA-6A10 Fab as a radioimmunotherapy agent targeting carbonic anhydrase XII. Nucl Med Biol. 2018 May;60:55-62. doi: 10.1016/j.nucmedbio.2018.02.004. Epub 2018 Mar 4.

  PMID: 29571067 BACKGROUND

• Alterio V, Kellner M, Esposito D, Liesche-Starnecker F, Bua S, Supuran CT, Monti SM, Zeidler R, De Simone G. Biochemical and Structural Insights into Carbonic Anhydrase XII/Fab6A10 Complex. J Mol Biol. 2019 Dec 6;431(24):4910-4921. doi: 10.1016/j.jmb.2019.10.022. Epub 2019 Nov 1.

  PMID: 31682835 BACKGROUND

• Battke C, Kremmer E, Mysliwietz J, Gondi G, Dumitru C, Brandau S, Lang S, Vullo D, Supuran C, Zeidler R. Generation and characterization of the first inhibitory antibody targeting tumour-associated carbonic anhydrase XII. Cancer Immunol Immunother. 2011 May;60(5):649-58. doi: 10.1007/s00262-011-0980-z. Epub 2011 Feb 5.

  PMID: 21298264 BACKGROUND

• Gondi G, Mysliwietz J, Hulikova A, Jen JP, Swietach P, Kremmer E, Zeidler R. Antitumor efficacy of a monoclonal antibody that inhibits the activity of cancer-associated carbonic anhydrase XII. Cancer Res. 2013 Nov 1;73(21):6494-503. doi: 10.1158/0008-5472.CAN-13-1110. Epub 2013 Sep 12.

  PMID: 24030978 BACKGROUND

• Proescholdt MA, Mayer C, Kubitza M, Schubert T, Liao SY, Stanbridge EJ, Ivanov S, Oldfield EH, Brawanski A, Merrill MJ. Expression of hypoxia-inducible carbonic anhydrases in brain tumors. Neuro Oncol. 2005 Oct;7(4):465-75. doi: 10.1215/S1152851705000025.

  PMID: 16212811 BACKGROUND

• Supuran CT. Carbonic anhydrase inhibitors as emerging agents for the treatment and imaging of hypoxic tumors. Expert Opin Investig Drugs. 2018 Dec;27(12):963-970. doi: 10.1080/13543784.2018.1548608. Epub 2018 Nov 22.

  PMID: 30426805 BACKGROUND

Study Officials

• Walter Stummer, Prof.

  University Hospital Muenster, Klinik und Poliklinik für Neurochirurgie

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A modified 3+3 design is used. The applied dose of Lu-177-labeled-6A10Fab-fragments to the resection cavity will be escalated in three cohorts until the maximum tolerated dose (MTD) is determined.

Study Record Dates

• First Submitted: July 25, 2022
• First Posted: September 8, 2022
• Study Start: January 22, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2027
• Last Updated: May 13, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (7)