Fluorescein for Brain Tumor Diagnosis

Recruiting at 1 trial location

Overseen By Keith D Paulsen, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: David W. Roberts

Disqualifiers: Pregnancy, Liver disease, Photosensitivity, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

30 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have a history of liver disease or elevated liver function tests, this may affect your eligibility.

What data supports the effectiveness of the drug Fluorescein for brain tumor diagnosis?

Research shows that sodium fluorescein is effective in brain tumor surgeries because it accumulates in tumor tissues, making them more visible and easier to distinguish from normal brain tissue. This helps surgeons remove tumors more accurately. ^{1 2 3 4 5}

Is fluorescein safe for use in brain tumor diagnosis?

Fluorescein sodium is considered highly safe and has been widely used in brain tumor surgeries to help distinguish tumor tissue from normal brain tissue. It is inexpensive, easy to use, and does not require special equipment, although its definitive role in pediatric cases is still being studied. ^{1 3 6 7 8}

How does the drug fluorescein differ from other treatments for brain tumors?

Fluorescein is unique because it is a fluorescent dye that accumulates in brain tumors with a damaged blood-brain barrier, allowing surgeons to see the tumor more clearly during surgery. This helps in distinguishing tumor tissue from normal brain tissue, potentially leading to more complete tumor removal. ^{1 2 3 8 9}

Research Team

David W Roberts, MD

Principal Investigator

Dartmouth-Hitchcock Medical Center

Eligibility Criteria

This trial is for adults over 21 with a first-time diagnosis of operable brain tumors, specifically high-grade or low-grade gliomas. Candidates must be able to give informed consent and not have serious psychiatric illnesses. Pregnant women, individuals with recent liver disease, abnormal liver function tests, high serum creatinine levels, or those sensitive to light due to medication cannot participate.

Inclusion Criteria

I am diagnosed with a type of brain tumor (glioma) for the first time.

Valid informed consent by subject or subject's LAR

I am 21 years old or older.

Exclusion Criteria

Pregnant women or women who are breast feeding

Inability to comply with the photosensitivity precautions associated with the study

I have had liver disease in the past year.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Participants undergo open cranial surgery for tumor resection with administration of fluorescein and/or ALA

1 day

1 visit (in-person)

Follow-up

Participants are monitored for adverse events through routine follow-up under the care of the operating surgeon

24 months

Treatment Details

Interventions

• Fluorescein
• Fluorescein + ALA

Trial Overview The study is testing the effectiveness of fluorescein as a marker during brain surgery when viewed through special microscopes. It's compared against MRI scans before surgery, another dye called ALA that also lights up under microscope light, and actual tissue samples from the tumor.

Participant Groups

Group I: Fluorescein + ALA Experimental Treatment 1 Intervention

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.

Group II: Fluorescein Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

David W. Roberts

Lead Sponsor

Trials

3

Recruited

680+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Carl Zeiss Meditec, Inc.

Industry Sponsor

Trials

24

Recruited

5,700+

Findings from Research

Sodium fluorescein is a safe and effective fluorescent dye used in neurosurgery, as demonstrated by a case where a patient received a potentially toxic dose (almost 3 g) without any toxic clinical effects during glioma surgery.

Despite challenges in visualization due to intense hyper-fluorescence, the procedure successfully achieved complete tumor resection, reinforcing the dye's utility in distinguishing between tumor and normal brain tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safeness of sodium fluorescein administration in neurosurgery: Case-report of an erroneous very high-dose administration and review of the literature. Restelli, F., Bonomo, G., Monti, E., et al.[2023]

In a study involving 28 patients undergoing 30 surgeries, sodium fluorescein (Na-Fl) was found to be highly effective for tumor demarcation, aiding in the identification of tumor tissue in 97% of operations.

The use of Na-Fl led to total resection in 79% of cases, demonstrating its potential to enhance surgical outcomes for high-grade gliomas and metastatic tumors, with no reported adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of the YELLOW 560 nm surgical microscope filter for sodium fluorescein-guided resection of brain tumors: Our preliminary results in a series of 28 patients. Hamamcıoğlu, MK., Akçakaya, MO., Göker, B., et al.[2022]

In a study involving 11 patients with benign neuroepithelial brain tumors, high-dose fluorescein-sodium (20mg/kg) effectively highlighted tumor tissue during surgery, leading to complete resection in 10 cases and confirming the presence of tumor in all fluorescein-positive specimens.

No complications were observed from the use of high-dose fluorescein, suggesting it is a safe and useful technique for improving the surgical delineation of benign brain tumors with contrast enhancement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative fluorescein staining for benign brain tumors. Minkin, K., Naydenov, E., Gabrovski, K., et al.[2017]

Sodium fluorescein (SF) is a safe and effective fluorescent dye that enhances the visibility of brain tumors during surgery by accumulating in areas with a damaged blood-brain barrier, improving tumor resection outcomes.

Over 1,099 neuro-oncological patients have undergone fluorescein-assisted surgeries since 2012, primarily for high-grade gliomas, although there is currently no standardized protocol for its use in neurosurgical oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The utilization of fluorescein in brain tumor surgery: a systematic review. Cavallo, C., De Laurentis, C., Vetrano, IG., et al.[2019]

In a review of 150 glioblastoma surgeries, the use of sodium fluorescein (FLS-Na) significantly increased the rate of total tumor resection (77.5% vs 27.1% with white light alone), indicating its efficacy in improving surgical outcomes.

Patients who underwent total resection with FLS-Na had a median overall survival of 15 months, compared to 8 months for those who did not receive FLS-Na, highlighting its potential impact on survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Microsurgical resection of glioblastoma guided with intraoperative fluorescein: a Retrospective evaluation]. García-Corrochano, P., Castañeda, CA., Orrego, E., et al.[2018]

Sodium fluorescein is a promising fluorescent dye for enhancing the visibility of tumors during pediatric neurosurgery due to its safety profile and ability to diffuse in areas with altered blood-brain barrier, which is common in pediatric tumors.

Despite its potential benefits, there is currently limited research specifically addressing the use of sodium fluorescein in children, highlighting the need for more studies to establish its definitive role in pediatric oncological neurosurgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focus session on sodium fluorescein in pediatric oncological neurosurgery. Di Rocco, F., de Laurentis, C.[2023]

Fluorescence-guided resection using high-dose fluorescein sodium has been successfully applied in 13 cases of metastatic brain tumors, achieving effective tumor staining in all instances.

Fluorescein sodium is a safe, cost-effective, and user-friendly option for enhancing tumor visibility during surgery, potentially improving the outcomes of metastatic brain tumor resections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metastatic brain tumor surgery using fluorescein sodium: technical note. Okuda, T., Kataoka, K., Taneda, M.[2015]

In a study of 117 patients with cerebral metastases, the use of sodium fluorescein during surgery significantly increased the extent of tumor resection compared to traditional white light methods.

Importantly, the use of fluorescein did not lead to any increase in postoperative neurological complications, suggesting it is a safe and effective tool for enhancing surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluorescein-guided resection of cerebral metastases is associated with greater tumor resection. Kofoed, MS., Pedersen, CB., Schulz, MK., et al.[2022]

Fluorescein (FS) is a safe and cost-effective agent used during brain tumor surgeries, allowing for better visualization of malignant gliomas by highlighting tumoral tissue under specific lighting conditions.

The use of a YELLOW 560 nm filter with an operating microscope significantly enhances the effectiveness of FS, enabling complete resection of high-grade gliomas while minimizing the required dosage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluorescein-Guided Surgery for Malignant Gliomas. Dellaretti, M., Melo, MT., Faraj de Lima, FB., et al.[2023]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Safeness of sodium fluorescein administration in neurosurgery: Case-report of an erroneous very high-dose administration and review of the literature. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

The use of the YELLOW 560 nm surgical microscope filter for sodium fluorescein-guided resection of brain tumors: Our preliminary results in a series of 28 patients. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Intraoperative fluorescein staining for benign brain tumors. [2017]

4. Italy pubmed.ncbi.nlm.nih.gov

The utilization of fluorescein in brain tumor surgery: a systematic review. [2019]

5. Peru pubmed.ncbi.nlm.nih.gov

[Microsurgical resection of glioblastoma guided with intraoperative fluorescein: a Retrospective evaluation]. [2018]

6. Germany pubmed.ncbi.nlm.nih.gov

Focus session on sodium fluorescein in pediatric oncological neurosurgery. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

Metastatic brain tumor surgery using fluorescein sodium: technical note. [2015]

8. Austria pubmed.ncbi.nlm.nih.gov

Fluorescein-guided resection of cerebral metastases is associated with greater tumor resection. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Fluorescein-Guided Surgery for Malignant Gliomas. [2023]