Intravital Microscopy in Human Solid Tumors

NCT03823144 | Recruiting FDA Device

• 2 other identifiers: 18-010370NCI-2021-02676
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Solid Tumor, Adult; Clinical Stage IV Gastric Cancer AJCC v8; Malignant Solid Neoplasm; Metastatic Primary Malignant Brain Neoplasm; Metastatic Sarcoma; Postneoadjuvant Therapy Stage IV Gastric Cancer AJCC v8; Resectable Colorectal Carcinoma; Resectable Liver and Intrahepatic Bile Duct Carcinoma; Resectable Pancreatic Carcinoma; Resectable Sarcoma; Stage IV Colorectal Cancer AJCC v8; Anatomic Stage IV Breast Cancer AJCC v8; Malignant Brain Neoplasm; Metastatic Breast Carcinoma; Metastatic Liver Carcinoma; Metastatic Pancreatic Carcinoma; Resectable Brain Neoplasm; Resectable Breast Carcinoma; Resectable Gastric Carcinoma; Stage IV Hepatocellular Carcinoma AJCC v8; Stage IV Pancreatic Cancer AJCC v8; Metastatic Colorectal Carcinoma; Metastatic Gastric Carcinoma

Outcome Measures

Primary Outcomes (4)

• 1. Tumor vessel identification (# tumor vessels visualized per high power field)

  Identify and measure vessels associated with solid tumors

  12-15 minutes

• 2. Tumor vessel density (# tumor vessels per square cm area observed)

  Determine vessel density per 10x field

  12-15 minutes

• 3. Fluorescent dye uptake (# tumor vessels with fluorescent dye uptake and # tumor vessels without dye uptake)

  Visualize vital dye within the vessels (fluorescein)

  12-15 minutes

• 4. Tumor blood flow (velocity, mm/sec)

  Calculate the blood flow velocity of the vessels and tissue penetration of fluorescent dye as a marker of vessel permeability.

  12-15 minutes

Secondary Outcomes (3)

• 5. Post-operative comparison of the microvasculature of tumor with normal tissue

  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).

  5-7 days

• Post-operative correlation of the microscopic observation of the tumor microvasculature tumor-specific and overall survival.

  5 years

Study Arms (1)

Arm 1

EXPERIMENTAL

Determine the feasibility and clinical utility of performing Human Intravital Microscopy (HIVM) in patients with solid tumors during surgical resection.

Device: Diagnostic Microscopy; Drug: Fluorescein Sodium Injection

Interventions

Diagnostic Microscopy DEVICE

Undergo Intravital microscopy (IVM), which allows real-time, direct visualization of microscopic blood vessels and calculation of blood flow.

Also known as: Human Intravital Microscopy, IVM, HIVM

Arm 1

Fluorescein Sodium Injection DRUG

Given IV as part of IVM procedure

Also known as: AK-Fluor, Fluorescite

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

RECRUITING

Related Publications (22)

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• Entenberg D, Kedrin D, Wyckoff J, Sahai E, Condeelis J, Segall JE. Imaging tumor cell movement in vivo. Curr Protoc Cell Biol. 2013 Mar;Chapter 19:19.7.1-19.7.19. doi: 10.1002/0471143030.cb1907s58.

  PMID: 23456602 RESULT

• McLaughlin RA, Scolaro L, Robbins P, Hamza S, Saunders C, Sampson DD. Imaging of human lymph nodes using optical coherence tomography: potential for staging cancer. Cancer Res. 2010 Apr 1;70(7):2579-84. doi: 10.1158/0008-5472.CAN-09-4062. Epub 2010 Mar 16.

  PMID: 20233873 RESULT

• Patsialou A, Bravo-Cordero JJ, Wang Y, Entenberg D, Liu H, Clarke M, Condeelis JS. Intravital multiphoton imaging reveals multicellular streaming as a crucial component of in vivo cell migration in human breast tumors. Intravital. 2013 Apr 1;2(2):e25294. doi: 10.4161/intv.25294.

  PMID: 25013744 RESULT

• Franko J, Shi Q, Goldman CD, Pockaj BA, Nelson GD, Goldberg RM, Pitot HC, Grothey A, Alberts SR, Sargent DJ. Treatment of colorectal peritoneal carcinomatosis with systemic chemotherapy: a pooled analysis of north central cancer treatment group phase III trials N9741 and N9841. J Clin Oncol. 2012 Jan 20;30(3):263-7. doi: 10.1200/JCO.2011.37.1039. Epub 2011 Dec 12.

  PMID: 22162570 RESULT

• Glehen O, Gilly FN, Boutitie F, Bereder JM, Quenet F, Sideris L, Mansvelt B, Lorimier G, Msika S, Elias D; French Surgical Association. Toward curative treatment of peritoneal carcinomatosis from nonovarian origin by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy: a multi-institutional study of 1,290 patients. Cancer. 2010 Dec 15;116(24):5608-18. doi: 10.1002/cncr.25356. Epub 2010 Aug 24.

  PMID: 20737573 RESULT

• Elias D, Gilly F, Boutitie F, Quenet F, Bereder JM, Mansvelt B, Lorimier G, Dube P, Glehen O. Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study. J Clin Oncol. 2010 Jan 1;28(1):63-8. doi: 10.1200/JCO.2009.23.9285. Epub 2009 Nov 16.

  PMID: 19917863 RESULT

• Glehen O, Gilly FN, Arvieux C, Cotte E, Boutitie F, Mansvelt B, Bereder JM, Lorimier G, Quenet F, Elias D; Association Francaise de Chirurgie. Peritoneal carcinomatosis from gastric cancer: a multi-institutional study of 159 patients treated by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy. Ann Surg Oncol. 2010 Sep;17(9):2370-7. doi: 10.1245/s10434-010-1039-7. Epub 2010 Mar 25.

  PMID: 20336386 RESULT

• Kalogeromitros DC, Makris MP, Aggelides XS, Mellios AI, Giannoula FC, Sideri KA, Rouvas AA, Theodossiadis PG. Allergy skin testing in predicting adverse reactions to fluorescein: a prospective clinical study. Acta Ophthalmol. 2011 Aug;89(5):480-3. doi: 10.1111/j.1755-3768.2009.01722.x. Epub 2009 Nov 10.

  PMID: 19906081 RESULT

• Jaffer FA. Intravital fluorescence microscopic molecular imaging of atherosclerosis. Methods Mol Biol. 2011;680:131-40. doi: 10.1007/978-1-60761-901-7_9.

  PMID: 21153378 RESULT

• Munn LL, Padera TP. Imaging the lymphatic system. Microvasc Res. 2014 Nov;96:55-63. doi: 10.1016/j.mvr.2014.06.006. Epub 2014 Jun 21.

  PMID: 24956510 RESULT

• Wolfe DR. Fluorescein angiography basic science and engineering. Ophthalmology. 1986 Dec;93(12):1617-20. doi: 10.1016/s0161-6420(86)33521-8.

  PMID: 3808620 RESULT

• Bloom JN, Herman DC, Elin RJ, Sliva CA, Ruddel ME, Nussenblatt RB, Palestine AG. Intravenous fluorescein interference with clinical laboratory tests. Am J Ophthalmol. 1989 Oct 15;108(4):375-9. doi: 10.1016/s0002-9394(14)73304-5.

  PMID: 2801858 RESULT

• Gabriel EM, Sukniam K, Popp K, Bagaria SP. Human intravital microscopy in the study of sarcomas: an early trial of feasibility. Front Oncol. 2023 Apr 12;13:1151255. doi: 10.3389/fonc.2023.1151255. eCollection 2023.

  PMID: 37124504 DERIVED

• Gabriel EM, Kim M, Fisher DT, Mangum C, Attwood K, Ji W, Mukhopadhyay D, Bagaria SP, Robertson MW, Dinh TA, Knutson KL, Skitzki JJ, Wallace MB. A pilot trial of intravital microscopy in the study of the tumor vasculature of patients with peritoneal carcinomatosis. Sci Rep. 2021 Mar 2;11(1):4946. doi: 10.1038/s41598-021-84430-3.

  PMID: 33654117 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Colorectal Neoplasms; Stomach Neoplasms; Sarcoma; Cholangiocarcinoma; Brain Neoplasms; Breast Neoplasms; Carcinoma, Hepatocellular; Pancreatic Neoplasms

Interventions

Fluorescein; Fluoresceins

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Stomach Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Liver Neoplasms; Liver Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Spiro Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Xanthenes; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Polycyclic Compounds

Study Officials

• Emmanuel M Gabriel, M.D., Ph.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emmanuel M Gabriel, M.D., Ph.D.

CONTACT

904-953-2523; gabriel.emmanuel@mayo.edu

Michael B Wallace, M.D.

CONTACT

904-953-2221; wallace.michael@mayo.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: This is an open-label, non-randomized, single center, study of IVM observation in conjunction with fluorescein in subjects with solid tumors undergoing surgical resection.
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2019
• First Posted: January 30, 2019
• Study Start: February 28, 2019
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: June 2, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)