Trial Title:
Radioimmunotherapy With Lu-177 Labeled 6A10 Fab-fragments in Patients With Glioblastoma After Standard Treatment
NCT ID:
NCT05533242
Condition:
Glioblastom WHO Grade 4
Conditions: Official terms:
Glioblastoma
Immunoglobulin Fab Fragments
Conditions: Keywords:
Carbonic anhydrase XII (CA XII)
Intracavitary radioimmunotherapy
Fab fragment 6A10
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Intervention model description:
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.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Lu-177 labeled 6A10-Fab-fragments
Description:
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.
Arm group label:
Lu-177-labeled-6A10Fab-fragments
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 the Grosshadern Hospital Munich, and supported by ITM and Helmholtz Munich.
Criteria for eligibility:
Criteria:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Klinik für Neurochirurgie des Universitätsklinikums Essen
Address:
City:
Essen
Zip:
45147
Country:
Germany
Status:
Recruiting
Facility:
Name:
Klinik für Nuklearmedizin, Strahlenklinik des Universitätsklinikums Essen
Address:
City:
Essen
Zip:
45147
Country:
Germany
Status:
Recruiting
Facility:
Name:
Klinik für Allgemeine Neurochirurgie des Universitätsklinikums Köln
Address:
City:
Köln
Zip:
50937
Country:
Germany
Status:
Recruiting
Facility:
Name:
Klinik für Nuklearmedizin des Universitätsklinikums Köln
Address:
City:
Köln
Zip:
50937
Country:
Germany
Status:
Recruiting
Facility:
Name:
Klinik für Nuklearmedizin der Universität Münster
Address:
City:
Münster
Zip:
48149
Country:
Germany
Status:
Recruiting
Facility:
Name:
Universitätsklinikum Würzburg - Neurochirurgie
Address:
City:
Würzburg
Zip:
97080
Country:
Germany
Status:
Recruiting
Facility:
Name:
Universitätsklinikum Würzburg - Nuklearmedizin
Address:
City:
Würzburg
Zip:
97080
Country:
Germany
Status:
Recruiting
Start date:
January 22, 2024
Completion date:
June 2025
Lead sponsor:
Agency:
University Hospital Muenster
Agency class:
Other
Collaborator:
Agency:
Isotope Technologies Munich (ITM) Oncologics
Agency class:
Other
Collaborator:
Agency:
Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH)
Agency class:
Other
Source:
University Hospital Muenster
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05533242
