Fluorescence-Guided Imaging of Brain Tumors: A Safety Study Using SBK2-ICG

Официальное название

Fluorescence-Guided Imaging of Brain Tumors: A Safety Study Using SBK2- ICG in a Phase 1 Clinical Trial

Обзор

Participants in this research study are people who are likely to have, or have been diagnosed with a brain tumor, for which surgical removal (or "resection") is the standard of care treatment. The purpose of this study is to see whether a drug called SBK2-ICG can be used to locate the true outline or "edges" of the tumor. If the tumor outline could be accurately identified at the time of surgery, the fullest extent of tumor could be removed while sparing the normal brain tissue. Participants will receive SBK2-ICG about an hour before they receive surgery. The extent of surgery to be performed will not be changed in this study. Researchers will only use the information from the study to determine the best SBK2-ICG dose for accurate tumor margin (i.e., the border or edges of the tumor with the normal brain) detection so that no tumor is left behind. The use of SBK2-ICG in brain tumors is experimental, which means that the U.S. Food and Drug Administration (FDA) has not approved it for use to locate brain tumors. However, the use of the drug SBK2-ICG for the purposes of this study is on file with the FDA.

Подробное описание

Treating people with serious brain tumors is challenging, and the outlook for these people is poor. On average, people survive less than one year after their are diagnosed. How long someone lives after diagnosis and treatment may depend on how much of the tumor is able to be removed with surgery. However, it can be difficult for surgeons to tell the difference between where the tumor is and where healthy brain tissue is using standard white light surgical microscope illumination. Because of this, new methods to help surgeons see tumor borders more clearly during surgery could be valuable.

Fluorescence imaging may be one method that can help surgeons see tumor borders more clearly. Previous studies have used fluorescence imaging to better visualize tumors, but no previous studies have used SBK2-ICG. In fact, the use of SBK2-ICG is conceptually different than other studies.

Currently, the only FDA approved drug used in fluorescent imaging for visualizing brain tumors during surgery is called 5-aminolevulinic acid, or 5-ALA. 5-ALA is naturally metabolized in human cells to something called PpIX. When people are given 5-ALA before surgery, it gets turned into PpIX, which can then be excited by fluorescent light at wavelengths of 400-410 nm. Because tumor cells and healthy cells metabolize 5-ALA in different ways, PpIX tends to accumulate in epithelial and malignant cells, including brain tumor cells. In a review of previous studies, using 5-ALA was associated with better removal of tumor tissue, longer overall survival, and longer progression-free survival. However, 5-ALA only weakly detects tumor borders and does not identify infiltrative cells on the edges of tumors. Also, even thin barriers of normal cells can make it difficult for surgeons to see 5-ALA, which makes it difficult to tell the difference between tumor tissue and healthy tissue. Because of this, it would be helpful to use a drug that emits a light that more deeply penetrates brain tissue so that surgeons can see tumor tissue and healthy tissue better.

SBK2-ICG is different than 5-ALA because it is not metabolized by the human body. Instead, SBK2-ICG attaches to a unique piece of cells that accumulates in tumors. SBK2-ICG can also be excited at a wavelength of 789 nm, rather than the wavelength of 400-410 nm that 5-ALA is excited at. SBK2-ICG gives off a near infrared light when it is excited, making it easier to see the borders of tumors. It also helps with seeing deep inside of the tumor. Using SBK2-ICG and fluorescent light has been shown to identify more than 99% of tumor cells in rodent xenograft models of human brain tumors in the lab.

Researchers want to assess the safety of SBK2-ICG in people with brain tumors who are already planning to have surgery to remove their tumor and see how SBK2-ICG compares to standard practices in identifying tumor tissue versus healthy tissue.

Вмешательства

• Препарат SBK2-ICG
  Participants will receive a single intravenous (IV) dose of SBK2-ICG one hour prior to their craniotomy (brain surgery). The starting dose is 0.072 mg/kg. The dose may be adjusted based on participants experiencing adverse events or based on participant response and fluorescence detection. If the 0.072mg/kg dose is well tolerated, researchers will examine fluorescence. If there are no Grade II or higher adverse events and researchers observe good fluorescence that is specific, researchers will c
• Процедура Craniotomy (Standard of Care)
  Participants will undergo a craniotomy (brain surgery) per standard of care. During the surgery, the study drug SBK2-ICG (given one hour prior to the surgery) and fluorescence light will be used to visualize the brain tumor(s). White light images (the standard of care) will also be used to visualize the tumor(s). The surgeon will take tissue biopsies based on standard of care processes.

Первичные конечные точки

• Safety of the imaging agent SBK2-ICG, as measured by prevalence of adverse events (AEs) [Срок оценки: Up to 14 days after surgery (Day 14)]

Вторичные конечные точки (2)

• Diagnostic performance of the imaging agent SBK2-ICG relative to 5-ALA [Срок оценки: Day of surgery (Day 1)]
• Clinical usefulness of the imaging agent SBK2-ICG for eventual fluorescence-guided resection, as measured by percent tumor present [Срок оценки: Day of surgery (Day 1)]

Критерии участия

Критерии включения

• Participants must have suspected or confirmed untreated malignant brain tumors
• Participants must have received no prior therapies for this disease.
• Participants are 18 years of age or older. Because no dosing or adverse event data are currently available on the use of SBK2-ICG in individuals under 18 years of age, children are excluded from this study.
• Karnofsky Performance status ≥ 60%
• Glioma is located in the supratentorial region of the brain.
• Tumor is suitable for resection on the basis of imaging studies and participant and surgeon must plan resection
• Able and willing to undergo MRI scan.
• Participants must have the ability to understand and the willingness to sign a written informed consent document

Критерии исключения

• Pregnant individuals or those who are breast feeding.
• Individuals with AST, ALT, ALP, or bilirubin >2.5x normal upper limit any time during the previous 2 months.
• Individuals with plasma creatinine > 2.5 mg/dL.
• Individuals without a probable or expected grade IV glioma.
• Individuals not planning surgery on glioma.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ICG or other agents used in this study.
• Note: A baseline blood sample will be drawn for creatinine, AST, ALT, ALP, and bilirubin to verify whether or not this exclusion criterion is met.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

США · 2 центра

• University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center — Cleveland
• Premier Health Neuroscience Institute — Dayton

Публикации

• Ostrom QT, Price M, Neff C, Cioffi G, Waite KA, Kruchko C, Barnholtz-Sloan JS. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2015-2019. Neuro Oncol. 2022 Oct 5;24(Suppl 5):v1-v95. doi: 10.1093/neuonc/noac202. PMID 36196752
• Chaichana KL, Parker SL, Mukherjee D, Cheng JS, Gokaslan ZL, McGirt MJ. Assessment of the extent of surgical resection as a predictor of survival in patients with primary osseous spinal neoplasms. Clin Neurosurg. 2011;58:117-21. doi: 10.1227/neu.0b013e318226fff7. No abstract available. PMID 21916135
• Keereweer S, Kerrebijn JD, van Driel PB, Xie B, Kaijzel EL, Snoeks TJ, Que I, Hutteman M, van der Vorst JR, Mieog JS, Vahrmeijer AL, van de Velde CJ, Baatenburg de Jong RJ, Lowik CW. Optical image-guided surgery--where do we stand? Mol Imaging Biol. 2011 Apr;13(2):199-207. doi: 10.1007/s11307-010-0373-2. PMID 20617389
• Gao X, Cui Y, Levenson RM, Chung LW, Nie S. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol. 2004 Aug;22(8):969-76. doi: 10.1038/nbt994. Epub 2004 Jul 18. PMID 15258594
• Richards-Kortum R, Sevick-Muraca E. Quantitative optical spectroscopy for tissue diagnosis. Annu Rev Phys Chem. 1996;47:555-606. doi: 10.1146/annurev.physchem.47.1.555. PMID 8930102
• Stummer W, Reulen HJ, Meinel T, Pichlmeier U, Schumacher W, Tonn JC, Rohde V, Oppel F, Turowski B, Woiciechowsky C, Franz K, Pietsch T; ALA-Glioma Study Group. Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias. Neurosurgery. 2008 Mar;62(3):564-76; discussion 564-76. doi: 10.1227/01.neu.0000317304.31579.17. PMID 18425006
• Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ; ALA-Glioma Study Group. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006 May;7(5):392-401. doi: 10.1016/S1470-2045(06)70665-9. PMID 16648043
• Marshall MV, Draney D, Sevick-Muraca EM, Olive DM. Single-dose intravenous toxicity study of IRDye 800CW in Sprague-Dawley rats. Mol Imaging Biol. 2010 Dec;12(6):583-94. doi: 10.1007/s11307-010-0317-x. PMID 20376568

Идентификаторы

NCT: NCT07438860 · CASE8325

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗