Intravital Microscopy in Human Solid Tumors

Solid Tumor, Adult Clinical Trial

Official title:

Intravital Microscopy (IVM) in Human Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03823144
• Other study ID #: 18-010370
• Secondary ID: NCI-2021-02676
• Status: Completed
• Phase: N/A
• Start date: February 28, 2019
• Est. completion date: December 31, 2023

Study information

• Verified date: January 2024
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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: 1. Compare the microscopic observation of the tumor-associated vessels with normal tissue (e.g. peritoneal surface or normal brain tissue) in each individual subject. 2. Correlate the microscopic observations of the tumor-associated vessels with pathologic grade of tumor. 3. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age = 18 years of age.

2. ECOG Performance Status of = 2.

3. Measurable tumor by direct visualization requiring surgical resection in the OR.

4. Tumor types of origin include gastric, pancreatic, hepatobiliary, colorectal, and sarcoma. Tumors may be primary or metastatic to solid or hollow intra-abdominal organs.

5. Subject must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent.

6. 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:

1. 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.

2. Renal dysfunction as defined as a GFR < 45.

3. Liver dysfunction as defined by Child-Pugh score > 5, or LFT's 1.5x above normal range.

4. Any known allergy or prior reaction to fluorescein or a positive skin prick test to fluorescein.

5. Pregnant or nursing female subjects, determined preoperatively with a urine pregnancy test.

6. Unwilling or unable to follow protocol requirements.

7. 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).

8. Any condition that excludes surgery as the standard of care (e.g. high disease burden where alternative treatments like systemic chemotherapy would be preferred).

Related Conditions & MeSH terms

• Brain Neoplasms
• Carcinoma
• Clinical Stage IV Gastric Cancer AJCC v8
• Colorectal Neoplasms
• Gastric Carcinoma
• Malignant Solid Neoplasm
• Metastatic Colorectal Carcinoma
• Metastatic Gastric Carcinoma
• Metastatic Sarcoma
• Neoplasms
• Pancreatic Neoplasms
• Postneoadjuvant Therapy Stage IV Gastric Cancer AJCC v8
• Resectable Colorectal Carcinoma
• Resectable Pancreatic Carcinoma
• Resectable Sarcoma
• Sarcoma
• Solid Tumor, Adult
• Stage IV Colorectal Cancer AJCC v8
• Stomach Neoplasms

Intervention

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

Drug:
• Fluorescein Sodium Injection
Given IV as part of IVM procedure

Locations

Country	Name	City	State
United States	Mayo Clinic Florida	Jacksonville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

References & Publications (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. — View Citation

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. — View Citation

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 multicent — View Citation

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. — View Citation

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 — View Citation

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. — View Citation

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 — View Citation

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. — View Citation

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 cytoreduct — View Citation

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 pe — View Citation

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. — View Citation

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. — View Citation

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 — View Citation

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 — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1. Tumor vessel identification (# tumor vessels visualized per high power field)	Identify and measure vessels associated with solid tumors	12-15 minutes
Primary	2. Tumor vessel density (# tumor vessels per square cm area observed)	Determine vessel density per 10x field	12-15 minutes
Primary	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
Primary	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	5. Post-operative comparison of the microvasculature of tumor with normal tissue	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
Secondary	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).	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
Secondary	Post-operative correlation of the microscopic observation of the tumor microvasculature tumor-specific and overall survival.	The investigators will determine if there is a correlation between the microscopic observation of the tumor microvasculature tumor-specific and overall survival.	5 years

External Links

•   Mayo Clinic Clinical Trials