- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03823144
Intravital Microscopy in Human Solid Tumors
January 29, 2024 updated by: Emmanuel M. Gabriel, Mayo Clinic
Intravital Microscopy (IVM) in Human Solid Tumors
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.
Study Overview
Status
Completed
Conditions
- Malignant Solid Neoplasm
- Gastric Carcinoma
- Solid Tumor, Adult
- Clinical Stage IV Gastric Cancer AJCC v8
- Metastatic Colorectal Carcinoma
- Stage IV Colorectal Cancer AJCC v8
- Metastatic Gastric Carcinoma
- Postneoadjuvant Therapy Stage IV Gastric Cancer AJCC v8
- Metastatic Sarcoma
- Resectable Pancreatic Carcinoma
- Resectable Colorectal Carcinoma
- Resectable Sarcoma
- Metastatic Primary Malignant Brain Neoplasm
- Resectable Liver and Intrahepatic Bile Duct Carcinoma
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVE: To determine the feasibility and clinical utility of performing HIVM in patients with solid tumors during standard course of treatment (surgical resection).
SECONDARY OBJECTIVES:
- Compare the microscopic observation of the tumor-associated vessels with normal tissue (e.g. peritoneal surface or normal brain tissue) in each individual subject.
- Correlate the microscopic observations of the tumor-associated vessels with pathologic grade of tumor.
- 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.
Study Type
Interventional
Enrollment (Actual)
41
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Emmanuel M Gabriel, M.D., Ph.D.
- Phone Number: 904-953-2523
- Email: gabriel.emmanuel@mayo.edu
Study Contact Backup
- Name: Michael B Wallace, M.D.
- Phone Number: 904-953-2221
- Email: wallace.michael@mayo.edu
Study Locations
-
-
Florida
-
Jacksonville, Florida, United States, 32224
- Mayo Clinic Florida
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Age ≥ 18 years of age.
- ECOG Performance Status of ≤ 2.
- Measurable tumor by direct visualization requiring surgical resection in the OR.
- Tumor types of origin include gastric, pancreatic, hepatobiliary, colorectal, and sarcoma. Tumors may be primary or metastatic to solid or hollow intra-abdominal organs.
- 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.
Exclusion Criteria:
- 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 GFR < 45.
- Liver dysfunction as defined by Child-Pugh score > 5, or LFT's 1.5x 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 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 surgery as the standard of care (e.g. high disease burden where alternative treatments like systemic chemotherapy would be preferred).
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm 1
Determine the feasibility and clinical utility of performing Human Intravital Microscopy (HIVM) in patients with solid tumors during surgical resection.
|
Undergo Intravital microscopy (IVM), which allows real-time, direct visualization of microscopic blood vessels and calculation of blood flow.
Other Names:
Given IV as part of IVM procedure
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
1. Tumor vessel identification (# tumor vessels visualized per high power field)
Time Frame: 12-15 minutes
|
Identify and measure vessels associated with solid tumors
|
12-15 minutes
|
2. Tumor vessel density (# tumor vessels per square cm area observed)
Time Frame: 12-15 minutes
|
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)
Time Frame: 12-15 minutes
|
Visualize vital dye within the vessels (fluorescein)
|
12-15 minutes
|
4. Tumor blood flow (velocity, mm/sec)
Time Frame: 12-15 minutes
|
Calculate the blood flow velocity of the vessels and tissue penetration of fluorescent dye as a marker of vessel permeability.
|
12-15 minutes
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Post-operative correlation of the microscopic observation of the tumor microvasculature tumor-specific and overall survival.
Time Frame: 5 years
|
The investigators will determine if there is a correlation between the microscopic observation of the tumor microvasculature tumor-specific and overall survival.
|
5 years
|
5. Post-operative comparison of the microvasculature of tumor with normal tissue
Time Frame: 15-20 minutes
|
Post-operative comparison of the microvasculature of tumor with normal tissue (e.g.
peritoneum) in each individual subject using vessel diameters, vessel density, detection of intravital dye and flow rates.
|
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).
Time Frame: 5-7 days
|
The investigators will determine if there is a correlation between 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
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Emmanuel M Gabriel, M.D., Ph.D., Mayo Clinic
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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. Erratum In: J Clin Oncol. 2010 Apr 1;28(10):1808.
- 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.
- 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.
- 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.
- 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.
- Wolfe DR. Fluorescein angiography basic science and engineering. Ophthalmology. 1986 Dec;93(12):1617-20. doi: 10.1016/s0161-6420(86)33521-8.
- 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.
- 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.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 28, 2019
Primary Completion (Actual)
December 31, 2023
Study Completion (Actual)
December 31, 2023
Study Registration Dates
First Submitted
January 28, 2019
First Submitted That Met QC Criteria
January 28, 2019
First Posted (Actual)
January 30, 2019
Study Record Updates
Last Update Posted (Actual)
January 31, 2024
Last Update Submitted That Met QC Criteria
January 29, 2024
Last Verified
January 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Endocrine System Diseases
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Stomach Diseases
- Endocrine Gland Neoplasms
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Central Nervous System Neoplasms
- Nervous System Neoplasms
- Pancreatic Diseases
- Neoplasms
- Sarcoma
- Stomach Neoplasms
- Carcinoma
- Colorectal Neoplasms
- Brain Neoplasms
- Pancreatic Neoplasms
Other Study ID Numbers
- 18-010370
- NCI-2021-02676 (Registry Identifier: CTRP (Clinical Trials Reporting Program))
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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