Diagnostic Performance of Fluorescein as an Intraoperative Brain Tumor Biomarker

David W. Roberts

Status and phase: Enrolling; Phase 2

Conditions: Brain Cancer

Treatments: Drug: Fluorescein + ALA; Drug: Fluorescein

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT02691923

R01NS052274-01A2 (U.S. NIH Grant/Contract)

D12090

Details and patient eligibility

About

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.

Full description

Consenting subjects who have met inclusion and exclusion criteria will be enrolled to receive either fluorescein+ALA or fluorescein alone. HGG patients will be randomized on a 2 to 1 basis to receive either both fluorescein and ALA or fluorescein alone, and LGG patients will be randomized on a 1 to 1 basis.

This study is a diagnostic trial of fluorescein fluorescence as an intraoperative imaging biomarker during open cranial surgery for tumor resection of first-time (preoperatively) presumed high or low grade glioma. Subjects participate in a "one-time" event/visit (i.e, surgery) as part of this protocol. Images and data from the patient's pre- and post-operative MR scans are used for analysis in the study, but these acquisitions are part of the patient's standard-of-care, would occur independently of whether the participant is enrolled; and thus, are not considered to be research study visits. No post-surgical follow-up visit is part of the protocol data collection or analysis. Patients are monitored for possible adverse events through the routine follow-up under the care of the operating surgeon involved in the study procedures, post-operatively and subsequently through the medical record. Hence, this information is already being collected as part of standard-of-care and is available for adverse event surveillance. Patients receiving ALA who present with abnormally elevated LFTs beyond the peri-operative observation period are monitored on a regular basis until resolution and this blood testing is considered to be part of the study.

Administration of study drug:

Patients enrolled in the fluorescein+ALA arm will be administered orally 5-ALA (DUSA Pharmaceuticals, Tarrytown, NY) at 20 mg/kg body weight, dissolved in 100 ml of water, approximately 3 hours prior to the induction of anesthesia.

For patients receiving only fluorescein, the operating surgeon will request bolus injection (at a dose of 5 mg/kg) approximately 30 minutes prior to the start of tumor resection. For especially long cases (e.g., > 4 h) or if fluorescein fluorescence dissipates substantially during the course of the procedure, a second bolus injection may occur later in the case.

Enrollment: 30 estimated patients

Sex: All

Ages: 21+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

1. Pregnant women or women who are breast feeding.
2. History of hypersensitivity to fluorescein.
3. History of cutaneous photosensitivity, porphyria, hypersensitivity to porphyrins, photodermatosis, exfoliative dermatitis.
4. History of liver disease within the last 12 months.
5. 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.
6. Serum creatinine in excess of 180µmol/L (2.04 md/dL) within 30 days prior to surgery.
7. Inability to comply with the photosensitivity precautions associated with the study.

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 2 patient groups

Fluorescein

Active Comparator group

Description:

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.

Treatment:

Drug: Fluorescein

Fluorescein + ALA

Experimental group

Description:

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.

Treatment:

Drug: Fluorescein + ALA