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

• Status: Not yet recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital Muenster
• Collaborators: Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH); Isotope Technologies Munich (ITM) Oncologics
• Treatments: Immunoglobulin Fab Fragments

Criteria

Inclusion Criteria:

• Written patient consent after comprehensive information

• Age between 18 and 70 years

• Primary supratentorial glioblastoma, after standard therapy (fluorescence-guided surgery, radio-chemotherapy, concomitant + adjuvant chemotherapy), with no or minimal tumor residue (tumor volume less than 1.0 cm3) at least 6 months after surgery

• Histological verification of glioblastoma and CA 12-expression of tumor cells confirmed

• Karnofsky-score ≥ 70

• Volume of resection cavity 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)

• GBM with intraventricular access

• Significant leakage of radioactivity into CSF spaces or ventricles

• Other invasive malignancy within 2 years (except for non-invasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has/have been surgically cured)

• 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)

• Participation in another clinical trial with therapeutic intervention or use of any other therapeutic interventional agent other than the standard therapy since diagnosis of glioblastoma

• Allergy against known constituents of study medication