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Evaluation of the CONVIVO System

Primary Purpose

Glioblastoma, Glial Tumor, Brain Metastases

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
CONVIVO system
Conventional histologic evaluation
Sponsored by
Dartmouth-Hitchcock Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Glioblastoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Adult patients (age>18)
  • Adults presenting with suspected intracranial gliomas (including glioblastoma), cerebral metastasis, meningiomas, acoustic neuromas, and pituitary adenomas, who are surgical candidates
  • Adults able to provide informed consent.

Exclusion Criteria:

  • Pregnancy
  • Children (age <18 years)
  • Fluorescein sodium (FNa) allergy

Sites / Locations

  • Dartmouth-Hitchcock Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

CONVIVO system

Conventional histologic evaluation

Arm Description

During tumor resection, study investigators trained in the use of the system will determine when the CONVIVO imaging system will be used for in vivo¬ imaging. At this point 5 mg/kg of fluorescein will be administered intravenously by an anesthesia provider over one minute.Approximately 2-5 minutes following administration of FNa in situ imaging will be performed by the participating surgeon ensuring proper technique.

Following image acquisition, the tissue region imaged with the CONVIVO system will then be biopsied using biopsy forceps. This will be passed immediately off the surgical field as a research specimen and provided to a member of the research team to be prepared for conventional histologic evaluation. The specimen will be labeled with the deidentified subject and sample number. This sequence will then be repeated for each successive sample.

Outcomes

Primary Outcome Measures

Diagnostic performance of CONVIVO in discriminating between normal and abnormal tissue
Concordance between in vivo imaging with the CONVIVO system and conventional histologic assessment.The diagnostic performance of the CONVIVO system will be assessed with respect to classification as "normal" or "abnormal" tissue. The interpretation of intraoperative images obtained in situ will be tested against conventional histologic evaluation of targeted biopsies from imaged tissue. Pertinent tumors include all intracranial neoplasms including low and high grade glial neoplasms, glioneuronal tumors, cerebral metastasis, meningioma, schwannoma, and pituitary lesions.

Secondary Outcome Measures

Degree of concordance with histologic diagnosis
Degree of concordance between in vivo imaging with the CONVIVO system and conventional histologic assessment or frozen with respect to histologic diagnosis.
Sensitivity and Specificity of CONVIVO system
Sensitivity and specificity analysis of CONVIVO using area under the curve and receiver operating characteristics. Conventional histopathology will be the gold-standard.
Rate of uninterpretable or non-diagnostic imaging with the CONVIVO system.
Rate of uninterpretable or non-diagnostic imaging with the CONVIVO system. During the resection the PI or other investigators may image tissue that is ultimately not biopsied. For example at the end of resection if there is a region of interest that cannot be safely resected, the CONVIVO system can be used to image the tissue without obtaining a corresponding tissue specimen for histology. During image acquisition it will be noted and documented by the research team that there is not a corresponding tissue specimen.
Correlation between intra-operative confocal microscopy and co-registered MRI points.
MRI characteristics will include (i) the presence or absence of contrast enhancement; (ii) signal intensity on T2 weighted images; (iii) perfusion based and spectroscopy imaging; (iv) diffusion weighted sequences.
Correlation between visible yellow-light fluorescence (560 nm filter) and intraoperative confocal microscopy.
Following image coregistration, the 560 yellow light filter on the Kinevo microscope will be used to determine the visible fluorescence in the region that was interrogated and classified from 0 to 4 based upon the fluorescence intensity. This will be recorded by the research team. The degree of visible fluorescence will be graded as 0-no fluorescence, 1- weak intensity, 2-moderate intensity, 3-strong intensity.
Correlation between visible blue-light fluorescence and quantitative fluorescence measurements
If the participant has also received 5-ALA, the 400 nm blue light filter will then be selected and the visible fluorescence of PPIX will also be classified from 0 to 4 based upon the fluorescence intensity. The degree of visible fluorescence will be graded as 0-no fluorescence, 1- weak intensity, 2- moderate intensity, 3-strong intensity.
Extent of tumor resection
Extent of resection has been found to be associated with increased overall and progression free survival, with the greatest benefit occurring in the setting of a complete or gross total resection. Postoperative MRI is obtained as appropriate, as it relates to extent of resection.
Adverse events related to the administration of fluorescein
Record adverse events as reported by participant or observed by investigator related to the administration of fluorescein
Time to interpretation of imaging and histology
Time to pathologic interpretation of intraoperative imaging compared to conventional interpretation of histology.Currently, the frozen section provides intraoperative histopathological analysis of brain tumors. Though useful, this process is time consuming and requires the cutting, freezing, and staining of several biopsies.
Ability to discriminate between viable tumor and pseudoprogression or "treatment effect" using the CONVIVO system.
The WHO criteria for the diagnosis of Glioblastoma (GBM) - cell density, cellular pleomorphism, increased mitoses, microvascular proliferation and trpalisading or ischemic necrosis - were all detectable by Confocal EndoMicroscope (CEM). Identification of the infiltration zone or the center of the tumor was possible based upon assessments of cell density comparing the center and border specimens. Additional aspects, e.g. apoptotic figures in perinecrotic pseudopalisading tumor cells, and important histological structures such as giant cells, fibrillary tumor matrix and blood vessels were also visible with CEM. Typical features of CEM in patients with histologically proven meningioma were also seen.

Full Information

First Posted
November 4, 2021
Last Updated
August 29, 2023
Sponsor
Dartmouth-Hitchcock Medical Center
Collaborators
Carl Zeiss Meditec, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05139277
Brief Title
Evaluation of the CONVIVO System
Official Title
Clinical Investigation to Evaluate the CONVIVO System for Discrimination of Normal From Abnormal Tissue During Brain Tumor Resection
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 28, 2022 (Actual)
Primary Completion Date
June 2025 (Anticipated)
Study Completion Date
June 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dartmouth-Hitchcock Medical Center
Collaborators
Carl Zeiss Meditec, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No

5. Study Description

Brief Summary
The primary objective of this study is to evaluate the diagnostic performance of the CONVIVO confocal endomicroscope in discriminating between normal and abnormal tissue in vivo during brain tumor surgery. The interpretation of intraoperative images obtained in situ will be tested against conventional histologic evaluation of targeted biopsies from imaged tissue. The study team hypothesize that there will be a high degree of correlation between images obtained with the CONVIVO system and conventional histologic interpretation.
Detailed Description
The surgical resection of brain tumors is an integral component of modern neuro-oncology. . Extent of resection has been found to be associated with increased overall and progression free survival, with the greatest benefit occurring in the setting of a complete or gross total resection. Unfortunately, there are a number of obstacles unique to brain tumors that may limit the extent of resection. A number of advancements in neurosurgical oncology have emerged to improve the extent of tumor resection while decreasing operative morbidity and mortality. Confocal reflectance microscopy is a routine technique used to visualize tissues without fixation or staining used in classical histological techniques. Laser scanning confocal microscopy (LSCM) is an optical fluorescence imaging modality used for imaging thick in vivo and ex vivo tissues. Clinically available confocal endomicroscopy systems contain lasers with precise excitation wavelengths and dichroic filters for detecting appropriate emission wave lengths. The studies completed to date do not evaluate the ability of confocal microscopy to discriminate between normal and abnormal tissue at the margins during surgical resection. This is the first of such in vivo feasibility studies that aims to demonstrate this claim of the CONVIVO system. The images acquired with the CONVIVO system following administration of fluorescein will be compared to conventional histologic specimens from corresponding biopsies. This is a planned single center study. This study is designed to assess the diagnostic accuracy of the CONVIVO system compared with gold-standard histopathology in tissue that has already been identified for resection. The device will not be used to inform surgical decision making, nor will tissue that would not otherwise be resected be biopsied for research purposes. This study will rely on study investigators, all physicians at Dartmouth-Hitchcock, to identify subjects. Written consent is required for participation in the study.. There are no specific medical risks to patients associated with the use of CONVIVO. It is not anticipated that there are immediate or direct benefits to patients participating in this study. The CONVIVO imaging data acquired during the procedure will be initially stored on the device's hard drive and later securely uploaded to an encrypted Dartmouth-Hitchcock server. Patients will have the ability to maintain their privacy with minimal disruption or contact by the study team. Additionally, the PI or other investigators will have interactions with the patient as part of their routine clinical care. Participants are free to withdraw from participation in the study at any time upon request.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma, Glial Tumor, Brain Metastases, Meningioma, Schwannoma, Pituitary Tumor

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Adult patients (age>18) presenting with suspected intracranial gliomas (including glioblastoma), cerebral metastasis, meningiomas, acoustic neuromas, and pituitary adenomas, who are surgical candidates and provide informed consent.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CONVIVO system
Arm Type
Experimental
Arm Description
During tumor resection, study investigators trained in the use of the system will determine when the CONVIVO imaging system will be used for in vivo¬ imaging. At this point 5 mg/kg of fluorescein will be administered intravenously by an anesthesia provider over one minute.Approximately 2-5 minutes following administration of FNa in situ imaging will be performed by the participating surgeon ensuring proper technique.
Arm Title
Conventional histologic evaluation
Arm Type
Other
Arm Description
Following image acquisition, the tissue region imaged with the CONVIVO system will then be biopsied using biopsy forceps. This will be passed immediately off the surgical field as a research specimen and provided to a member of the research team to be prepared for conventional histologic evaluation. The specimen will be labeled with the deidentified subject and sample number. This sequence will then be repeated for each successive sample.
Intervention Type
Diagnostic Test
Intervention Name(s)
CONVIVO system
Intervention Description
Approximately 2-5 minutes following administration of FNa in situ imaging will be performed by the participating surgeon ensuring proper technique. Prior to entering the surgical field, the probe will be covered in a disposable sterile sheath that is manufactured with quality assurance for this purpose. The probe will gently be held against the tissue interface while imaging occurs. Again this will only be in regions that would normally be resected or sampled in routine clinical care. Following image acquisition, a neuropathologist present in the operating room, will review and capture each image.
Intervention Type
Other
Intervention Name(s)
Conventional histologic evaluation
Intervention Description
Following image acquisition, the tissue region imaged with the CONVIVO system will then be biopsied using biopsy forceps. This will be passed immediately off the surgical field as a research specimen and provided to a member of the research team to be prepared for conventional histologic evaluation. The specimen will be labeled with the deidentified subject and sample number. This sequence will then be repeated for each successive sample.
Primary Outcome Measure Information:
Title
Diagnostic performance of CONVIVO in discriminating between normal and abnormal tissue
Description
Concordance between in vivo imaging with the CONVIVO system and conventional histologic assessment.The diagnostic performance of the CONVIVO system will be assessed with respect to classification as "normal" or "abnormal" tissue. The interpretation of intraoperative images obtained in situ will be tested against conventional histologic evaluation of targeted biopsies from imaged tissue. Pertinent tumors include all intracranial neoplasms including low and high grade glial neoplasms, glioneuronal tumors, cerebral metastasis, meningioma, schwannoma, and pituitary lesions.
Time Frame
On day of Surgery, Day 0
Secondary Outcome Measure Information:
Title
Degree of concordance with histologic diagnosis
Description
Degree of concordance between in vivo imaging with the CONVIVO system and conventional histologic assessment or frozen with respect to histologic diagnosis.
Time Frame
On day of surgery, Day 0
Title
Sensitivity and Specificity of CONVIVO system
Description
Sensitivity and specificity analysis of CONVIVO using area under the curve and receiver operating characteristics. Conventional histopathology will be the gold-standard.
Time Frame
On day of surgery, Day 0
Title
Rate of uninterpretable or non-diagnostic imaging with the CONVIVO system.
Description
Rate of uninterpretable or non-diagnostic imaging with the CONVIVO system. During the resection the PI or other investigators may image tissue that is ultimately not biopsied. For example at the end of resection if there is a region of interest that cannot be safely resected, the CONVIVO system can be used to image the tissue without obtaining a corresponding tissue specimen for histology. During image acquisition it will be noted and documented by the research team that there is not a corresponding tissue specimen.
Time Frame
On day of surgery, Day 0
Title
Correlation between intra-operative confocal microscopy and co-registered MRI points.
Description
MRI characteristics will include (i) the presence or absence of contrast enhancement; (ii) signal intensity on T2 weighted images; (iii) perfusion based and spectroscopy imaging; (iv) diffusion weighted sequences.
Time Frame
On day of surgery, Day 0
Title
Correlation between visible yellow-light fluorescence (560 nm filter) and intraoperative confocal microscopy.
Description
Following image coregistration, the 560 yellow light filter on the Kinevo microscope will be used to determine the visible fluorescence in the region that was interrogated and classified from 0 to 4 based upon the fluorescence intensity. This will be recorded by the research team. The degree of visible fluorescence will be graded as 0-no fluorescence, 1- weak intensity, 2-moderate intensity, 3-strong intensity.
Time Frame
On day of surgery, Day 0
Title
Correlation between visible blue-light fluorescence and quantitative fluorescence measurements
Description
If the participant has also received 5-ALA, the 400 nm blue light filter will then be selected and the visible fluorescence of PPIX will also be classified from 0 to 4 based upon the fluorescence intensity. The degree of visible fluorescence will be graded as 0-no fluorescence, 1- weak intensity, 2- moderate intensity, 3-strong intensity.
Time Frame
On day of surgery, Day 0
Title
Extent of tumor resection
Description
Extent of resection has been found to be associated with increased overall and progression free survival, with the greatest benefit occurring in the setting of a complete or gross total resection. Postoperative MRI is obtained as appropriate, as it relates to extent of resection.
Time Frame
2 Days after surgery up to one month.
Title
Adverse events related to the administration of fluorescein
Description
Record adverse events as reported by participant or observed by investigator related to the administration of fluorescein
Time Frame
Day of surgery (Day 0), 2 Days after surgery up to one month.
Title
Time to interpretation of imaging and histology
Description
Time to pathologic interpretation of intraoperative imaging compared to conventional interpretation of histology.Currently, the frozen section provides intraoperative histopathological analysis of brain tumors. Though useful, this process is time consuming and requires the cutting, freezing, and staining of several biopsies.
Time Frame
Day of surgery (Day 0), and up to one week
Title
Ability to discriminate between viable tumor and pseudoprogression or "treatment effect" using the CONVIVO system.
Description
The WHO criteria for the diagnosis of Glioblastoma (GBM) - cell density, cellular pleomorphism, increased mitoses, microvascular proliferation and trpalisading or ischemic necrosis - were all detectable by Confocal EndoMicroscope (CEM). Identification of the infiltration zone or the center of the tumor was possible based upon assessments of cell density comparing the center and border specimens. Additional aspects, e.g. apoptotic figures in perinecrotic pseudopalisading tumor cells, and important histological structures such as giant cells, fibrillary tumor matrix and blood vessels were also visible with CEM. Typical features of CEM in patients with histologically proven meningioma were also seen.
Time Frame
Day of surgery (Day 0) and up to one month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adult patients (age>18) Adults presenting with suspected intracranial gliomas (including glioblastoma), cerebral metastasis, meningiomas, acoustic neuromas, and pituitary adenomas, who are surgical candidates Adults able to provide informed consent. Exclusion Criteria: Pregnancy Children (age <18 years) Fluorescein sodium (FNa) allergy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Linton T Evans, MD
Phone
603-650-5026
Email
Linton.T.Evans@hitchcock.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Linton T Evans, MD
Organizational Affiliation
Dartmouth-Hitchcock Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dartmouth-Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Linton T Evans, MD
Phone
603-650-5026
Email
linton.t.evans@hitchcock.org
First Name & Middle Initial & Last Name & Degree
Linton T Evans, MD

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
There are no plans at this time to share IPD.

Learn more about this trial

Evaluation of the CONVIVO System

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