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

February 8, 2024 updated by: University Hospital Muenster

A Phase I Trial to Determine the Maximum Tolerated Dose and Patient-specific Dosimetry of Fractionated Intracavitary Radioimmunotherapy With Lu-177 Labeled 6A10 Fab-fragments in Patients With Glioblastoma After Standard Treatment

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

15

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Nils Warneke, Dr. med.

Study Locations

  • Germany
      • Essen, Germany, 45147
        • Recruiting
        • Klinik für Neurochirurgie des Universitätsklinikums Essen
      • Essen, Germany, 45147
        • Recruiting
        • Klinik für Nuklearmedizin, Strahlenklinik des Universitätsklinikums Essen
      • Köln, Germany, 50937
        • Recruiting
        • Klinik für Allgemeine Neurochirurgie des Universitätsklinikums Köln
      • Köln, Germany, 50937
        • Recruiting
        • Klinik für Nuklearmedizin des Universitätsklinikums Köln
      • Münster, Germany, 48149
        • Recruiting
        • Klinik für Nuklearmedizin der Universität Münster
      • Würzburg, Germany, 97080
        • Recruiting
        • Universitätsklinikum Würzburg - Neurochirurgie
      • Würzburg, Germany, 97080
        • Recruiting
        • Universitätsklinikum Würzburg - Nuklearmedizin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lu-177-labeled-6A10Fab-fragments
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
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Through study completion, ca 1 ½ years
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
Through study completion, ca 1 ½ years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
After first application: 2 ,24 ,48, 72 hours post injection and on day 5-7. After second and third application.
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
Through study completion, an average of 18 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: 2 years from the day of inclusion
OS is defined as the period of time from the start of a study or the treatment in a study until the death of the patient
2 years from the day of inclusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Muenster

Collaborators

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

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 22, 2024

Primary Completion (Estimated)

June 1, 2025

Study Completion (Estimated)

June 1, 2025

Study Registration Dates

First Submitted

July 25, 2022

First Submitted That Met QC Criteria

September 5, 2022

First Posted (Actual)

September 8, 2022

Study Record Updates

Last Update Posted (Actual)

February 9, 2024

Last Update Submitted That Met QC Criteria

February 8, 2024

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UKM15_0027

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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