Intravital Microscopy (IVM) in Patients With Peritoneal Carcinomatosis (PC)

NCT03517852 | Completed

• 1 other identifier: 17-009823
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate the tumor-associated vasculature of patients with peritoneal carcinomatosis, or cancer that spreads along the inner abdominal lining. The investigators will use a technology known as intravital microscopy (IVM) in order to visualize in real-time the tumor-associated vessels of peritoneal disease. 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

Peritoneal Carcinomatosis

Outcome Measures

Primary Outcomes (4)

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

  Identify and measure vessels associated with peritoneal tumor implants

  15-20 minutes

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

  Determine vessel density per 10x field

  15-20 minutes

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

  Visualize vital dyes within the vessels \[fluorescein and indocyanine green (ICG)\]

  15-20 minutes

• Tumor blood flow (velocity, mm/sec)

  Calculate the blood flow velocity of the vessels and tissue penetration of fluorescent dyes as markers of vessel permeability.

  15-20 minutes

Secondary Outcomes (3)

• Post-operative comparison of the microvasculature of peritoneal carcinomatosis with normal tissue (peritoneum)

  15-20 minutes

• 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 peritoneal carcinomatosis during standard course of treatment (cytoreductive surgery with hyperthermic intraperitoneal chemotherapy, or CRS-HIPEC).

Device: Human Intravital Microscopy

Interventions

Human Intravital Microscopy DEVICE

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

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.
• Have an ECOG Performance Status of ≤ 2. Refer to Appendix C.
• Have measurable disease in the peritoneum by direct visualization (visible lesion typically \> 0.5 cm in maximal diameter).
• Carcinomatosis that meets indications for CRS-HIPEC.
• Subject must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure.
• A negative skin-prick test 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 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 ICG 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).
• Any condition that excludes CRS-HIPEC as the standard of care for the patient.

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Nagy JA, Chang SH, Dvorak AM, Dvorak HF. Why are tumour blood vessels abnormal and why is it important to know? Br J Cancer. 2009 Mar 24;100(6):865-9. doi: 10.1038/sj.bjc.6604929. Epub 2009 Feb 24.

  PMID: 19240721 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Peritoneal Neoplasms

Condition Hierarchy (Ancestors)

Abdominal Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases

Study Officials

• Emmanuel M Gabriel, M.D., Ph.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

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 and ICG in subjects with peritoneal carcinomatosis undergoing CRS-HIPEC.
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 13, 2018
• First Posted: May 8, 2018
• Study Start: August 15, 2018
• Primary Completion: July 23, 2019
• Study Completion: December 31, 2023
• Last Updated: January 19, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)