Diagnostic Performance of Fluorescein as an Intraoperative Brain Tumor Biomarker

NCT02691923 | Recruiting Phase 2 DMC

• 2 other identifiers: D12090R01NS052274-01A2
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical research will evaluate the diagnostic potential of fluorescein as visualized through an operating microscope relative to 1) contrast enhancement on co-registered preoperative MR scans, 2) intraoperative ALA-induced PpIX fluorescence and 3) gold-standard histology obtained from biopsy sampling during the procedure. Subjects will include those people with operable brain tumor with first-time presumed pre-surgical diagnosis of high-grade glioma or low-grade glioma.

Conditions

Brain Cancer

Keywords

High Grade Glioma; Low Grade Glioma; Brain Tumor

Outcome Measures

Primary Outcomes (1)

• Fluorescein performance as an intraoperative biomarker for tumor tissue will be reported.

  The predictive performance of fluorescein fluorescence as an intraoperative imaging biomarker of tumor during surgery in patients with a clinical diagnosis of high grade glioma (HGG) and patients with a clinical diagnosis of low grade glioma (LGG) will be measured. Fluorescence will be measured both quantitatively via an intraoperative probe and visually by the neurosurgeon through the operating microscope. Endpoints will be assessed separately for HGG and LGG groups.

  24 months

Secondary Outcomes (2)

• Fluorescein performance as visualized and measured with an intraoperative probe will be reported

  24 months

• Fluorescein versus fluorescein + ALA performance will be reported in patients in patients with 2 different types of tumors

  24 months

Study Arms (2)

Fluorescein

ACTIVE COMPARATOR

Fluorescein administered IV at 5mg/kg approximately 30 minutes prior to the beginning of the tumor resection. A second injection may occur if the fluorescein fluorescence is dissipated substantially during the course of the procedure.

Drug: Fluorescein

Fluorescein + ALA

EXPERIMENTAL

Fluorescein administered IV at 5mg/kg approximately 30 minutes prior to the beginning of the tumor resection. A second injection may occur if the fluorescein fluorescence is dissipated substantially during the course of the procedure. ALA administered orally at 20mg/kg approximately 3 hours before surgery.

Drug: Fluorescein + ALA

Interventions

Fluorescein DRUG

Also known as: Fluorescite

Fluorescein

Fluorescein + ALA DRUG

Also known as: Flourescein = Fluorescite; ALA = 5-Aminolevulinic Acid

Fluorescein + ALA

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Preoperative diagnosis of either presumed first-time low or high grade glioma (astrocytoma, oligodendroglioma, mixed oligo-astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme).
• Tumor judged to be suitable for open cranial resection based on preoperative imaging studies.
• Valid informed consent by subject or subject's LAR.
• No serious associated psychiatric illnesses.
• Age ≥ 21 years old.

You may not qualify if:

• Pregnant women or women who are breast feeding.
• History of hypersensitivity to fluorescein.
• History of cutaneous photosensitivity, porphyria, hypersensitivity to porphyrins, photodermatosis, exfoliative dermatitis.
• History of liver disease within the last 12 months.
• Elevated LFTs (AST, ALT, ALP or bilirubin levels greater than 2.5 times the normal limit) from laboratory tests conducted within 30 days prior to surgery.
• Serum creatinine in excess of 180µmol/L (2.04 md/dL) within 30 days prior to surgery.
• Inability to comply with the photosensitivity precautions associated with the study.

Sponsors & Collaborators

• David W. Roberts: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• Carl Zeiss Meditec, Inc.: collaborator

Study Sites (1)

Sally B Mansur

Lebanon, New Hampshire, 03756, United States

RECRUITING

Related Publications (3)

• Roberts DW, Valdes PA, Harris BT, Hartov A, Fan X, Ji S, Leblond F, Tosteson TD, Wilson BC, Paulsen KD. Glioblastoma multiforme treatment with clinical trials for surgical resection (aminolevulinic acid). Neurosurg Clin N Am. 2012 Jul;23(3):371-7. doi: 10.1016/j.nec.2012.04.001.

  PMID: 22748650 BACKGROUND

• Elliott JT, Dsouza AV, Davis SC, Olson JD, Paulsen KD, Roberts DW, Pogue BW. Review of fluorescence guided surgery visualization and overlay techniques. Biomed Opt Express. 2015 Sep 3;6(10):3765-82. doi: 10.1364/BOE.6.003765. eCollection 2015 Oct 1.

  PMID: 26504628 BACKGROUND

• Valdes PA, Jacobs V, Harris BT, Wilson BC, Leblond F, Paulsen KD, Roberts DW. Quantitative fluorescence using 5-aminolevulinic acid-induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery. J Neurosurg. 2015 Sep;123(3):771-80. doi: 10.3171/2014.12.JNS14391. Epub 2015 Jul 3.

  PMID: 26140489 BACKGROUND

MeSH Terms

Conditions

Brain Neoplasms; Glioma

Interventions

Fluorescein; Aminolevulinic Acid

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Fluoresceins; Spiro Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Xanthenes; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Polycyclic Compounds; Levulinic Acids; Keto Acids; Carboxylic Acids; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• David W Roberts, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sally B Mansur, MS

CONTACT

Sally.B.Mansur@Dartmouth.edu

Keith D Paulsen, PhD

CONTACT

Keith.D.Paulsen@Dartmouth.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Surgery (Neurosurgery)

Study Record Dates

• First Submitted: February 22, 2016
• First Posted: February 25, 2016
• Study Start: March 1, 2016
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)