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

Studien-Informationen Einschlusskriterien Studien-Rationale Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT05533242

Studienbeginn:
Januar 2024

Letztes Update:
09.02.2024

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

Indikation (Clinical Trials):
Glioblastoma

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
University Hospital Muenster

Collaborator:
Isotope Technologies Munich (ITM) Oncologics, Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH),

Studienleiter

Walter Stummer, Prof.
Principal Investigator
University Hospital Muenster, Klinik und Poliklinik für Neurochirurgie

Kontakt

Walter Stummer, Prof. Dr.
Kontakt:
Phone: 0049251/83-47472
E-Mail: walter.stummer@ukmuenster.de» Kontaktdaten anzeigen

Nils Warneke, Dr. med.

Studienlocations
(3 von 7)

Klinik für Neurochirurgie des Universitätsklinikums Essen
45147 Essen
(Nordrhein-Westfalen)
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Klinik für Nuklearmedizin, Strahlenklinik des Universitätsklinikums Essen
45147 Essen
(Nordrhein-Westfalen)
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Klinik für Allgemeine Neurochirurgie des Universitätsklinikums Köln
50937 Köln
(Nordrhein-Westfalen)
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Klinik für Nuklearmedizin des Universitätsklinikums Köln
50937 Köln
(Nordrhein-Westfalen)
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Klinik für Nuklearmedizin der Universität Münster
48149 Münster
(Nordrhein-Westfalen)
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Universitätsklinikum Würzburg - Neurochirurgie
97080 Würzburg
(Bayern)
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Universitätsklinikum Würzburg - Nuklearmedizin
97080 Würzburg
(Bayern)
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Alle anzeigen

Studien-Informationen

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 the Grosshadern Hospital Munich, and supported by ITM and Helmholtz Munich.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- 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

Exclusion Criteria:

- 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

Studien-Rationale

Primary outcome:

1. Maximum Tolerated Dose (MTD) (Time Frame - 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

2. Safety of the adjuvant radio-immunotherapy (Time Frame - 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:

1. Evaluation of pharmacokinetics of Lu-177 labeled 6A10 Fab fragments (Time Frame - 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)

2. Progression-free survival (PFS) (Time Frame - Through study completion, an average of 18 months):
Determining 24 weeks Progression-Free-Survival (PFS), defined from the day of inclusion

Geprüfte Regime

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.

Quelle: ClinicalTrials.gov

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