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.
Study 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
Eligibility
Sex
ALL
Min age
18 Years
Max age
80 Years
Healthy volunteers
No
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
Primary outcome measure(s)
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
Trial sites (7)
Facility
City
Region
Status
Klinik für Allgemeine Neurochirurgie des Universitätsklinikums Köln
Cologne
Germany
Klinik für Nuklearmedizin des Universitätsklinikums Köln
Cologne
Germany
Klinik für Neurochirurgie des Universitätsklinikums Essen
Essen
Germany
Klinik für Nuklearmedizin, Strahlenklinik des Universitätsklinikums Essen
Essen
Germany
Klinik für Nuklearmedizin der Universität Münster
Münster
Germany
Universitätsklinikum Würzburg - Neurochirurgie
Würzburg
Germany
Universitätsklinikum Würzburg - Nuklearmedizin
Würzburg
Germany
More University Hospital Muenster trials in Germany
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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