Intravital Microscopy in Human Solid Tumors

Официальное название

Intravital Microscopy (IVM) in Human Solid Tumors

Обзор

This study will investigate the tumor-associated vasculature of patients with solid tumors. The investigators will use a technology known as intravital microscopy (IVM) in order to visualize in real-time the vessels associated with solid tumors. The IVM observations may determine if an individual patient's tumor vessels would be amenable to receiving systemic therapy, based on the functionality of the vessels.

Подробное описание

PRIMARY OBJECTIVE:

I. To determine the feasibility of performing human intravital microscopy (HIVM) in patients with deep space solid tumors during standard course of surgical resection.

SECONDARY OBJECTIVES:

I. Compare the microscopic observation of the tumor-associated vessels with normal tissue (e.g. peritoneal surface or normal brain tissue) in each individual subject.

II. Correlate the microscopic observations of the tumor-associated vessels with pathologic grade of tumor.

III. To correlate the microscopic observation of the microvasculature with tumor-specific and overall survival.

OUTLINE:

Patients receive fluorescein intravenously (IV) and undergo HIVM over 1-2 minutes per field.

After completion of study, patients are followed up at 2-3 weeks after surgery.

Вмешательства

• Устройство Diagnostic Microscopy
  Undergo Intravital microscopy (IVM), which allows real-time, direct visualization of microscopic blood vessels and calculation of blood flow.
• Препарат Fluorescein Sodium Injection
  Given IV as part of IVM procedure

Первичные конечные точки

• 1. Tumor vessel identification (# tumor vessels visualized per high power field) [Срок оценки: 12-15 minutes]
• 2. Tumor vessel density (# tumor vessels per square cm area observed) [Срок оценки: 12-15 minutes]
• 3. Fluorescent dye uptake (# tumor vessels with fluorescent dye uptake and # tumor vessels without dye uptake) [Срок оценки: 12-15 minutes]
• 4. Tumor blood flow (velocity, mm/sec) [Срок оценки: 12-15 minutes]

Вторичные конечные точки (3)

• 5. Post-operative comparison of the microvasculature of tumor with normal tissue [Срок оценки: 15-20 minutes]
• 6. Post-operative correlation of the microvasculature with pathologic features of the tumor implants (i.e. tumor grade) at the time of the final pathology report (5-7 days after surgery). [Срок оценки: 5-7 days]
• Post-operative correlation of the microscopic observation of the tumor microvasculature tumor-specific and overall survival. [Срок оценки: 5 years]

Критерии участия

Критерии включения

• Age ≥ 18 years of age
• Eastern Cooperative Oncology Group (ECOG)Performance Status of ≤ 2
• Measurable tumor by direct visualization requiring surgical resection in the operating room (OR)
• Tumor types of origin include gastric, pancreatic, hepatobiliary, colorectal, sarcoma, brain, or breast cancer that may involve the axillary lymph nodes cancers. Tumors may be primary or metastatic
• Subject must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent
• Subject must have a skin prick test pre-operatively (at the time of the preoperative visit and after signed informed consent for entry into this clinical trial is given) to determine any sensitivity to fluorescein

Критерии исключения

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations
• Renal dysfunction as defined as a glomerular filtration rate (GFR) < 45
• Liver dysfunction as defined by Child-Pugh score > 5, or liver function test (LFT)'s 1.5 x above normal range
• Any known allergy or prior reaction to fluorescein or a positive skin prick test to fluorescein
• Pregnant or nursing female subjects, determined preoperatively with a urine pregnancy test
• Unwilling or unable to follow protocol requirements
• Any condition which in the investigators' opinion deems the patient unsuitable (e.g., abnormal electrocardiography \[EKG\], including T wave inversion, elevated T waves, prolonged QRS interval, or conduction blocks) or that requires further work-up (including cardiac echo or stress test)
• Any condition that excludes surgical resection as the standard of care for the patient

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 · 1 центр

• Mayo Clinic Florida — Jacksonville

Публикации

• Fisher DT, Chen Q, Skitzki JJ, Muhitch JB, Zhou L, Appenheimer MM, Vardam TD, Weis EL, Passanese J, Wang WC, Gollnick SO, Dewhirst MW, Rose-John S, Repasky EA, Baumann H, Evans SS. IL-6 trans-signaling licenses mouse and human tumor microvascular gateways for trafficking of cytotoxic T cells. J Clin Invest. 2011 Oct;121(10):3846-59. doi: 10.1172/JCI44952. Epub 2011 Sep 19. PMID 21926464
• Fisher DT, Muhitch JB, Kim M, Doyen KC, Bogner PN, Evans SS, Skitzki JJ. Intraoperative intravital microscopy permits the study of human tumour vessels. Nat Commun. 2016 Feb 17;7:10684. doi: 10.1038/ncomms10684. PMID 26883450
• Nagy JA, Chang SH, Shih SC, Dvorak AM, Dvorak HF. Heterogeneity of the tumor vasculature. Semin Thromb Hemost. 2010 Apr;36(3):321-31. doi: 10.1055/s-0030-1253454. Epub 2010 May 20. PMID 20490982
• Abdollahi A, Folkman J. Evading tumor evasion: current concepts and perspectives of anti-angiogenic cancer therapy. Drug Resist Updat. 2010 Feb-Apr;13(1-2):16-28. doi: 10.1016/j.drup.2009.12.001. Epub 2010 Jan 12. PMID 20061178
• Fukumura D, Duda DG, Munn LL, Jain RK. Tumor microvasculature and microenvironment: novel insights through intravital imaging in pre-clinical models. Microcirculation. 2010 Apr;17(3):206-25. doi: 10.1111/j.1549-8719.2010.00029.x. PMID 20374484
• Skitzki JJ, Chen Q, Wang WC, Evans SS. Primary immune surveillance: some like it hot. J Mol Med (Berl). 2007 Dec;85(12):1361-7. doi: 10.1007/s00109-007-0245-7. Epub 2007 Aug 18. PMID 17704903
• Jain RK, Munn LL, Fukumura D. Dissecting tumour pathophysiology using intravital microscopy. Nat Rev Cancer. 2002 Apr;2(4):266-76. doi: 10.1038/nrc778. PMID 12001988
• Murooka TT, Mempel TR. Multiphoton intravital microscopy to study lymphocyte motility in lymph nodes. Methods Mol Biol. 2012;757:247-57. doi: 10.1007/978-1-61779-166-6_16. PMID 21909917

Идентификаторы

NCT: NCT03823144 · 18-010370 · NCI-2021-02676

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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