ISRCTN ISRCTN10645335
DOI https://doi.org/10.1186/ISRCTN10645335
ClinicalTrials.gov number NCT03517852
Secondary identifying numbers 17-009823
Submission date
06/10/2020
Registration date
25/11/2020
Last edited
13/12/2024
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aims
This study will investigate the tumor-associated vessels 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 treatment, based on the functionality of the vessels.

Who can participate?
Patients who are undergoing surgery for peritoneal carcinomatosis

What does the study involve?
During surgery (CRS-HIPEC), a microscope will be used to directly observe the blood vessels associated with the tumor implants lining the peritoneum (abdominal lining). Intravenous (IV) dyes will be administered through catheters connected to veins in order to help enhance the microscopic observations. These dyes include a substance called fluorescein and indocyanine green, which are two generally safe and frequently used dyes for a variety of surgical procedures. Because there can be allergic reactions to fluorescein (less than 5% of cases), participants will be asked to undergo allergic skin testing to fluorescein before joining the study. This consists of a skin-prick test with a small drop of fluorescein to determine if they will have an allergic reaction. Various measurements of tumor vessels and blood flow through the vessels will be recorded.

What are the possible benefits and risks of participating?
It is not known if participation in this observational study will help or not. Possible help may include identifying tumor characteristics that may someday predict response or guide treatment in the future. Microscopic findings observed during the CRS-HIPEC may have a predictive value of PC response or recurrence. This would potentially result in improved prognostic information for you and other study participants. There is no guarantee of improved outcome for taking part in this study. Future patients may be helped from the results and information gained from this study. It is hoped that information gained in this study will aid in the understanding of cancer and help in the development of new approaches to its treatment.
It is anticipated that there will be minimal-to-no increased risk of adding a microscopic observation to the surgical procedure (CRS-HIPEC). There are, however, inherent risks to CRSHIPEC itself. Studies have shown the complications for which patients undergoing CRS-HIPEC are at risk, including: leaking from any bowel reconnections (only in the case that bowel removal is considered part of the procedure), prolonged recovery time of bowel function (known as an ileus), and/or a decrease in blood counts (such as white blood cells, known as neutropenia) that would be temporary. However, this study is unlikely to increase these risks.
Use of fluorescein may not be recommended in patients with a history of allergic hypersensitivity to fluorescein. Adverse reactions have been reported to occur in 5% or less of patients and are typically mild, including itching or hives. Adverse reactions to indocyanine green have been reported to be even lower with the incidences of mild, moderate and severe reactions to be 0.15%, 0.2% and 0.05%, respectively. Indocyanine green can cause an allergic reaction in patients who are allergic to iodine-based IV contrast dye, typically given during a CT scan. Participants who have an allergic reaction to iodine-based IV contrast dye will not be eligible to participate in this study.

Where is the study run from?
Mayo Clinic Florida (USA)

When is the study starting and how long is it expected to run for?
May 2018 to December 2024

Who is funding the study?
Mayo Clinic Florida Focused Research Teams (USA)

Who is the main contact?
Dr Emmanuel Gabriel
gabriel.emmanuel@mayo.edu

Study website

Contact information

Ms Mauricia Buchanan
Public

Mayo Clinic
4500 San Pablo Road
Jacksonville
32224
United States of America

Phone +1 (0)904 953 6691
Email buchanan.mauricia@mayo.edu
Dr Emmanuel Gabriel
Scientific

Mayo Clinic
4500 San Pablo Road
Jacksonville
32224
United States of America

Phone +1 (0)904 953 2523
Email Gabriel.Emmanuel@mayo.edu

Study information

Study designObservational single-arm pilot study
Primary study designObservational
Secondary study designCase series
Study setting(s)Hospital
Study typeDiagnostic
Participant information sheet https://clinicaltrials.gov/ProvidedDocs/52/NCT03517852/ICF_000.pdf
Scientific titleIntravital microscopy in patients with peritoneal carcinomatosis
Study acronymIVM PC
Study objectivesThis is an observational study. The purpose of this study is to evaluate the microscopic characteristics of the blood vessels associated with tumors that grow along the peritoneum. This type of study is investigational, and it is expected that the use of a special microscope will help visualize tumor-associated blood vessels and blood flow. This may lead to valuable information for physicians in the treatment of patients with this condition.
Ethics approval(s)Approved 04/03/2018, Mayo Clinic Institutional Review Board (Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, USA: +1 (0)866 273 4681; IRBE@mayo.edu), ref: 17-009823
Health condition(s) or problem(s) studiedPeritoneal carcinomatosis
InterventionDuring surgery (CRS-HIPEC), a microscope will be used to directly observe the blood vessels associated with the tumor implants lining the peritoneum (abdominal lining). Intravenous (IV) dyes will be administered through catheters connected to veins in order to help enhance the microscopic observations. These dyes include a substance called fluorescein and indocyanine green, which are two generally safe and frequently used dyes for a variety of surgical procedures. Because there can be allergic reactions to fluorescein (less than 5% of cases), participants will be asked to undergo allergic skin testing to fluorescein prior to enrollment in the study (as listed above). This consists of a skin-prick test with a small drop of fluorescein to determine if they will have an allergic reaction. Various measurements of tumor vessels and blood flow through the vessels will be recorded.
Intervention typeProcedure/Surgery
Primary outcome measure1. Identify and measure number of vessels associated with peritoneal tumor implants using intravital microscopy at the time of surgery (vessels visualized per high power field)
2. Tumor vessel density (tumor vessels per square cm area observed) as above
3. Number of tumor vessels with fluorescent dye uptake and number of tumor vessels without dye uptake)
4.Tumor blood flow (velocity, mm/sec) of the vessels and tissue penetration of fluorescent dyes as markers of vessel permeability using intravital microscopy at the time of surgery
Secondary outcome measures1. Diameters, vessel density, detection of intravital dye and flow rates of the microvasculature of peritoneal carcinomatosis compared with normal tissue using intravital microscopy at the time of surgery
2. Pathologic features of the tumor implants (i.e. tumor grade) measured by the investigators at the time of the final pathology report (5-7 days after surgery)
3. Overall survival at 1 and 2 years
Overall study start date08/05/2018
Completion date31/12/2024

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants30
Total final enrolment50
Key inclusion criteria1. Age ≥18 years of age
2. Have an ECOG Performance Status of ≤2
3. Have measurable disease in the peritoneum by direct visualization (visible lesion typically >0.5 cm in maximal diameter)
4. Carcinomatosis that meets indications for CRS-HIPEC
5. 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
6. A negative skin-prick test to fluorescein
Key exclusion criteria1. 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 the normal range
4. Any known allergy or prior reaction to fluorescein or ICG 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)
8. Any condition that excludes CRS-HIPEC as the standard of care for the patient
Date of first enrolment15/08/2018
Date of final enrolment31/12/2019

Locations

Countries of recruitment

  • United States of America

Study participating centre

Mayo Clinic Florida
4500 San Pablo Road
Jacksonville
32224
United States of America

Sponsor information

Mayo Clinic
Hospital/treatment centre

4500 San Pablo Road
Jacksonville
32224
United States of America

Phone +1 (0)866 273 4681
Email IRBE@mayo.edu
Website https://www.mayo.edu/research/centers-programs/cancer-research/cancer-clinical-trials/cancer-clinical-trials

Funders

Funder type

Hospital/treatment centre

Mayo Clinic Florida Focused Research Teams

No information available

Results and Publications

Intention to publish date31/12/2020
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryAvailable on request, Stored in repository
Publication and dissemination planPlanned publication in a high-impact peer-reviewed journal.
IPD sharing planCurrent individual participant data (IPD) sharing statement as of 06/01/2022:
The datasets generated during and/or analysed during the current study will be stored in a non-publically available repository and will be available on request from the study contact.

Previous individual participant data (IPD) sharing statement:
The datasets generated during and/or analysed during the current study will be stored in a non-publically available repository.

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article 02/03/2021 06/01/2022 Yes No

Editorial Notes

13/12/2024: The total final enrolment was changed from 30 to 50.
05/12/2023: Contact details updated.
06/01/2022: The following changes have been made:
1. Publication reference added.
2. The overall trial end date has been changed from 31/12/2019 to 31/12/2024 and the plain English summary has been updated accordingly.
3. The individual participant data (IPD) sharing statement has been updated and the IPD sharing summary "Available on request" has been added.
08/10/2020: Trial’s existence confirmed by Mayo Clinic IRB