Clinical Significance of Liquid Biopsy in Brain Tumor Patients: a 5-ALA Guided Approach (FLUO-LB)

August 27, 2026 updated by: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
Glioblastoma (GBM) is the most common and lethal primary brain tumor. Identifying blood biomarkers that reflect the tumor's status is a major unmet need for optimal clinical management. 5-ALA (5-Aminolevulinic Acid) administration leads to the accumulation of fluorescent Protoporphyrin IX (PpIX) in GBM cells, allowing identification during surgery. This project aims to leverage 5-ALA induced fluorescence to maximize the informational power of plasma liquid biopsy as a tool for diagnosis, post-treatment follow-up, and as a prognostic tool in patients with GBM.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

This is a prospective observational study. Patients with suspected brain tumors requiring 5-ALA fluorescence-guided surgery will be enrolled. Samples of plasma, serum, and urine will be collected at a minimum of two timepoints: once before 5-ALA administration (baseline, T1) and again 12 hours after administration (T2), when PpIX levels are expected to be highest. All sample collection and processing will occur in low-light conditions to prevent PpIX degradation. Samples will be stored at -80°C. Fluorometric analysis (Perkin Elmer Wallac 1420 Victor2 Microplate Reader) will be performed to measure PpIX fluorescence. Additionally, each patient will undergo a pre-operative MRI as per routine care to measure tumor volume, which will be correlated with fluorescence data.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

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

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Italy
      • Milan, Italy
        • Fondazione IRCCS Istituto Neurologico Carlo Besta

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

30 Patients with brain tumors whose treatment course involves fluorescence-guided surgery 5-ALA.

Description

Inclusion Criteria:

  • Inclusion Criteria (Glioblastoma Patients):
  • Patient aged 18 years or older
  • Diagnosis of supratentorial glioblastoma at its first occurrence (Grade 4, WHO 2021), confirmed through histological analysis, in a brain area that is accessible for surgical removal.
  • Ability of the patient to give informed consent.
  • Suitability for surgery with fluorescence guidance using 5-ALA.

Inclusion Criteria (Other Brain Tumors):

  • Patient aged 18 years or older
  • Ability of the patient to give informed consent.
  • Suitability for surgery with fluorescence guidance using 5-ALA.

Exclusion Criteria:

Exclusion Criteria (Glioblastoma Patients):

  • Presence of other systemic tumors.
  • Known allergic sensitivity or contraindications to gadolinium.
  • Contraindications to MRI, such as the presence of non-compatible implanted devices.
  • Significantly compromised renal function (eGFR <30 ml/min/1.73 m²), and/or patients undergoing dialysis.
  • Conditions that contraindicate surgery with fluorescence guidance using 5-ALA.

Exclusion Criteria (Other Brain Tumors):

  • Patients suffering from systemic tumors (besides the primary of the brain metastasis).
  • Individuals with known allergies or adverse reactions to gadolinium.
  • Individuals with contraindications for MRI, including those with implants not compatible with the procedure.
  • Individuals with significantly reduced kidney function (eGFR < 30 ml/min/1.73 m²), or those undergoing dialysis.

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

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Glioblastoma Patients
Patients aged 18 or older with a first diagnosis of supratentorial glioblastoma (WHO Grade 4), confirmed by histology, who are candidates for 5-ALA fluorescence-guided surgery.
Other Brain Tumor Patients
Patients aged 18 or older with other brain tumors (in differential diagnosis with glioblastoma) who are candidates for 5-ALA fluorescence-guided surgery.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Protoporphyrin IX (PpIX) Fluorescence Level in Glioblastoma Patients
Time Frame: 2 years
PpIX fluorescence level in blood (serum and plasma) and urine at different time-points (pre-administration, 12h post-administration, and potentially other timepoints depending on preliminary observations) in patients with glioblastoma.
2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
PpIX Fluorescence Level in Control/Other Brain Tumor Patients
Time Frame: 2 years
PpIX fluorescence level in blood (serum and plasma) and urine at different time-points in controls/patients with other brain tumor pathologies.
2 years
Correlation of Fluorescence with Histopathological Characteristics
Time Frame: 2 years
Correlation of PpIX fluorescence levels with histopathological characteristics of the tumor tissue.
2 years
Correlation of Fluorescence with Tumor Tissue Fluorescence
Time Frame: 2 years
Correlation of PpIX fluorescence levels in liquid biopsy (blood/urine) with the observed fluorescence of the tumor tissue during surgery
2 years
Correlation of Fluorescence with MRI Lesion Volumes
Time Frame: 2 years
Correlation of PpIX fluorescence levels with lesion volumes measured on pre-operative Magnetic Resonance Imaging (MRI).
2 years
Kinetics of 5-ALA-induced Fluorescence
Time Frame: 2 years
Describe the kinetics (changes over time) of 5-ALA-induced fluorescence in plasma and urine levels.
2 years

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Milan
Università degli Studi del Piemonte Orientale Amedeo Avogadro

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 27, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 2, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 11, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 19, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 28, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 27, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • FLUO-LB

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The Sponsor (Fondazione IRCCS Istituto Neurologico Carlo Besta) is the owner of the data resulting from the study. All Investigators participating in the study should be made aware of such circumstance and not to disseminate information or data without the prior written consent by the Sponsor

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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