Feasibility of Aspirate Tissue Monitoring in Neuro-oncological Surgery (ATM GBM INT)

Gliomas are tumors that occur in all ages; they include the most common malign primary central nervous system tumors in developed countries. Gliomas are often aggressive, and their recommended treatment is surgical resection and chemoradiation. Complete tumor removal is challenging because of diffuse cell growth and the proximity of functionally critical tissues. Surgeons use 5-aminolevulinic acid (5-ALA) drug-induced fluorescence to visually detect tumor cells, which improves resection rates and delays tumor progression. Tumor cells are often left unnoticed because of visual obstacles or weak fluorescence, which may lead to local recurrence and reoperations. Surgical suction devices are used to remove cancerous tissues, but so far the suction aspirate tissues have not been routinely used in tissue detection. This multicenter controlled clinical trial investigates the clinical performance and outcomes of a new method for detecting tumor from the suction aspirates in near-real time based on 5-ALA induced fluorescence. The feedback from the aspirate tissue monitor (ATM) is expected to improve the identification of tumors, leading to fewer reoperations and better treatment outcomes.

Study Overview

• Status: Recruiting
• Conditions: High Grade Gliomas
• Intervention / Treatment: Device: Aspirate tissue monitoring; Device: Fluorescence-guided surgery

Detailed Description

During glioma surgery, the diffuse boundary between healthy tissue and tumor is localized using 5-ALA drug-enhanced fluorescence of cancer cells. Visual fluorescence-based tissue recognition technique using 5-ALA has been shown to improve the rate of tumor removal and slow disease progression. To see the fluorescence typical of cancer, a special light source is needed in the operating microscope. In typical blue light, the fluorescence is visible, but it is more difficult detect anatomical landmarks, such as cerebral blood vessels and cranial nerves, which makes them vulnerable to injuries. Tumor cells can also be unnoticed because of visual obstacles or weak fluorescence, which may lead to local recurrence and reoperations. Unintended tumor remnants are frequent even though many other auxiliary techniques such as MRI guidance, neuronavigation, ultrasound and neurophysiological monitoring are used.

This multicenter controlled clinical trial investigates the clinical performance and outcomes from using an aspirate tissue monitor (ATM, Marginum Ltd HIVEN™) that detects cancerous tissue from the suction waste during the surgical treatment of suspected high-grade gliomas. The ATM provides near real-time audible feedback to the surgeon when tumor-related fluorescence is detected in the aspirated tissues. The trial investigates if the use of ATM to detect 5-ALA induced fluorescence contributes to faster tumor removal, less blood loss, less unintended residual tumor, less morbidity, longer survival and the frequency of local reoperations.

In total fifty (n=50) patients referred for resection surgery for suspected high-grade glioma or its recurrence at the Kuopio University Hospital, Tampere University Hospital and Oslo University Hospital, and potential other trial sites, will be recruited to the study. The patients are prescribed oral 5-ALA preoperatively according to the institution's practices. The cases are compared with controls (n=50) from applicable local clinical site registers (matched controls). The cases are operated with the help of aspirate tissue monitoring and the controls without. Other preferred adjunct techniques are used in both groups.

Informed written consent will be obtained from patients to participate in the study on the new surgical device. The clinical trial is approved by the local research ethics committees and approved by the Finnish Medicines Agency (Fimea) and Norwegian Medicines Agency (NoMA). Patients are asked for permission to pool unidentified study data from surgical patients collected at different research institutions. The investigated device is a CE equivalent or CE marked.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sami Puustinen, PhD; Phone Number: +358442190767; Email: sami.puustinen@marginum.com
• Study Contact Backup: Name: Antti-Pekka Elomaa, Docent; Email: antti-pekka.elomaa@pshyvinvointialue.fi

Study Locations

• Finland
  • Pirkanmaa
    • Tampere, Pirkanmaa, Finland
      • Recruiting
      • Tampere University Hospital
      • Contact: Joonas Haapasalo, Docent; Email: joonas.haapasalo@pirha.fi
  • Pohjois-Savo
    • Kuopio, Pohjois-Savo, Finland
      • Recruiting
      • Kuopio University Hospital
      • Contact: Antti-Pekka Elomaa, Docent; Email: antti-pekka.elomaa@marginum.com
• Norway
  • Oslo, Norway
    • Not yet recruiting
    • Oslo University Hospital
    • Contact: Einar Vik-Mo, Professor; Email: uxvieb@ous-hf.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient admitted to neurosurgery department for surgical resection of a suspected high-grade glioma
• Patients aged 18 years old or older
• Informed consent obtained

Exclusion Criteria:

• Patient belongs to the following vulnerable groups: children, pregnant, prisoners or intellectually disabled

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aspirate tissue monitoring; In total fifty (n=50) patients referred for resection surgery for suspected high-grade glioma or its recurrence at the Kuopio University Hospital, Tampere University Hospital and Oslo University Hospital, and potential other trial sites, will be recruited to the study. The patients are prescribed oral 5-ALA preoperatively according to the institution's practices. The cases are operated with the help of aspirate tissue monitoring and the controls without. Other preferred adjunct techniques are used in both groups.	Device: Aspirate tissue monitoring; This multicenter controlled clinical trial investigates the clinical performance and outcomes from using an aspirate tissue monitor (ATM, Marginum Ltd HIVEN™) that detects cancerous tissue from the suction waste during the surgical treatment of suspected high-grade gliomas. The ATM provides near real-time audible feedback to the surgeon when tumor-related fluorescence is detected in the aspirated tissues. The trial investigates if the use of ATM to detect 5-ALA induced fluorescence contributes to faster tumor removal, less blood loss, less unintended residual tumor, less morbidity, longer survival and the frequency of local reoperations. The cases are compared with controls (n=50) from applicable local clinical site registers (matched controls). The cases are operated with the help of aspirate tissue monitoring and the controls without. Other preferred adjunct techniques are used in both groups.
Active Comparator: Fluorescence-guided surgery; The cases are compared with controls (n=50) from applicable local clinical site registers (matched controls).	Device: Fluorescence-guided surgery; Resection utilizing conventional visual fluorescence-guided surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extent of resection (EOR)	The extent of resection (EOR) of the tumor is investigated.	four years
Overall survival (OS)	The effects on the overall survival (OS) are investigated.	four years
Progression-free survival (PFS)	The effects on the progression-free survival (PFS) are investigated.	four years
Karnofsky Performance Scale (KPS)	Improved patients' postoperative performance KPS	four years
Amount of reoperations	The effects on the amount of reoperations are investigated.	four years
Blood loss during the operation	The effects on the blood loss during the operation (ml) are investigated.	four years
Duration of the operation	The effects on the duration of the operation (min) are investigated.	four years

Collaborators and Investigators

• Sponsor: Kuopio University Hospital
• Collaborators: Oslo University Hospital; Tampere University Hospital; Marginum Ltd.
• Investigators: Principal Investigator: Antti-Pekka Elomaa, Docent, Kuopio University Hospital; Principal Investigator: Joonas Haapasalo, Docent, Tampere University Hospital; Principal Investigator: Einar Vik-Mo, Professor, Oslo University Hospital

Publications and helpful links

General Publications

• Intraoperative aspirate tissue monitoring during 5-ALA fluorescence-guided surgery of high-grade glioma - the first-in-human observational cases https://doi.org/10.1016/j.bas.2023.102121

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2024
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: October 30, 2024
• First Submitted That Met QC Criteria: December 13, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 13, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: 5-ALA; high-grade glioma; neurosurgery; fluorescence-guided surgery; aspirate tissue monitoring
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma
• Other Study ID Numbers: 5252675

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: GDPR limitations.

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