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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether fluorescein, a special dye, can help doctors better visualize brain tumors during surgery. It compares this dye to other methods, such as MRI scans and tissue tests, to determine if it provides a clearer picture. Two treatment groups exist: one using only fluorescein and another combining it with ALA, another substance believed to enhance visibility. Individuals recently diagnosed with a surgically removable brain tumor might be suitable for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that fluorescein is generally safe and well-tolerated. It has long been used in eye treatments and more recently in brain surgeries. Studies indicate that it helps surgeons see brain tumors more clearly, making them easier to remove. This dye is considered relatively non-toxic even when injected into a vein.

The combination of fluorescein with 5-ALA, a light-sensitive drug, has also been studied. Research shows that using both helps doctors see tumors in real-time during surgery. This combination is safe and well-tolerated, providing a cost-effective way to guide brain surgery. Together, these treatments help doctors find and remove brain tumors more effectively, with minimal side effects reported. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using fluorescein and ALA for brain tumor diagnosis because these treatments offer a unique approach to improving surgical outcomes. Unlike standard practices that rely on MRI and CT scans, fluorescein is administered intravenously to make the tumor fluoresce, providing real-time visual guidance during surgery. The combination with ALA, taken orally, further enhances tumor visualization under special lighting, potentially leading to more precise tumor removal. This method promises to increase the accuracy of resections, minimizing healthy brain tissue damage and improving patient recovery.

What evidence suggests that this trial's treatments could be effective for brain tumor diagnosis?

Research has shown that fluorescein, one of the treatments in this trial, can significantly aid brain tumor surgery. In one study, 69% of patients had their tumors completely removed with fluorescein, compared to 36% without it. Another study reported an 82.6% success rate for full tumor removal in surgeries for aggressive brain tumors using fluorescein.

In this trial, some participants will receive fluorescein alone, while others will receive a combination of fluorescein and ALA, a substance that makes cancer cells glow. Studies suggest this combination effectively identifies and removes tumor edges. Both treatments are considered safe and enhance the surgeon's ability to see the tumor clearly during operations. ^{1 2 3 6 7}

Who Is on the Research Team?

David W Roberts, MD

Principal Investigator

Dartmouth-Hitchcock Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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 (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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12449807/

Surgical efficacy and survival outcomes of fluorescein sodium ... GTR was achieved in 69 % of FS cases versus 36 % with WL (p = 0.0004; OR = 1.379). FS significantly reduced residual tumor volume (1.82 ml vs.

2. sciencedirect.com sciencedirect.com/science/article/pii/S277252942200844X

Case-report of an erroneous very high-dose administration ... The good clinical and laboratory outcome of this patient further strengthens the idea that fluorescein-guided removal of brain tumors may be considered safe, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8245059/

Fluorescence-Guided Surgery: A Review on Timing and Use ... found that fluorescein was safe and effective in HGG surgery, with a GTR rate of 82.6% and 6-month progression-free survival of 56.6% (35). ICG, a fluorophore ...

4. link.springer.com link.springer.com/article/10.1007/s00701-024-06223-7

Sodium fluorescein-guided resection of brain metastases This study aimed to evaluate the efficacy of FL FGS in improving the extent of resection of brain metastases and its impact on overall survival.

5. frontiersin.org frontiersin.org/journals/surgery/articles/10.3389/fsurg.2019.00049/full

Fluorescein Application in Cranial and Spinal Tumors ... Fluorescein-guided surgery with a dedicated filter on the microscope is a safe and effective technique to improve visualization and resection of different CNS ...

6. aacrjournals.org aacrjournals.org/clincancerres/article/24/1/52/15206/Fluorescein-Guided-Surgery-for-Resection-of-High

Fluorescein-Guided Surgery for Resection of High-Grade ... The sensitivity and specificity of fluorescein in identifying tumor tissue were estimated by fluorescent and nonfluorescent biopsies at the tumor margin. The ...

7. thejns.org thejns.org/view/journals/j-neurosurg/140/4/article-p958.xml

Sodium fluorescein uptake by the tumor microenvironment in ... Fluorescein has been used for many years for diagnostic purposes and is considered relatively nontoxic, even when administered intravenously.