Intracranial TumorPhase 2INVIVONCT04597801
Comparison of Fluorescein-INtra-VItal Microscopy Versus Conventional Frozen Section Diagnosis for intraOperative Histopathological Evaluation
A Phase 2 study testing Alcon in people with Intracranial Tumor, run by Technical University of Munich at 3 sites in Germany.
Trial summary
With the appliance of the in-vivo microscopy after Fluorescein staining, the investigators hypothesize that the preliminary in-vivo histopathological diagnostic accuracy is not inferior to conventional frozen section analysis accuracy when using the final histopathological result as gold standard. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Intracranial Tumor
- What is being tested?
- Alcon
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 210 participants
- Where
- 3 sitesGermany
- Study dates
- 30 Dec 2020to 3 Aug 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years
- Signed informed consent
- Suspected intracranial tumor revealed by cranial magnetic resonance imaging (according to clinical routine) scheduled for resection with intraoperative frozen section evaluation
Who cannot join
- Known allergic or suspected allergic reactions to fluorescein sodium
- Liver disease, CHILD B or C
- Patients under medication with beta-blockers, digoxin, chinidin and probenecid as well as inhibitors of glucuronidation, such as immunosuppressants, when the medication must not be discontinued perioperatively
- Patients with relevant congenital limitations of glucuronidation performance (e.g. Rotor syndrome, Gilbert-Meulengracht syndrome, Crigler-Najjar syndrome)
- Patients with terminal renal failure requiring hemodialysis
- Inability to provide informed consent
- Pregnancy (incl. positive pregnancy test)
- Women of childbearing age must be non-lactating and surgically sterile or using a highly effective method of birth control and have a negative pregnancy test. Acceptable methods of birth control with a low failure rate (i.e. less than 1% per year) when used consistently and correct are such as implants, injectables, combined oral contraceptives, hormonal intrauterine devices (IUDs), sexual abstinence or vasectomized partner.
Trial locations and contacts
3 sites in 1 country.
Germany3 sites
Universitätsklinikum Mannheim
Mannheim, 68167
Technische Universität München, Klinik und Poliklinik für Neurochirurgie
München, 81675
Universitätsklinikum Regensburg
Regensburg, 93053
About this study
Official title: Comparison of Fluorescein-INtra-VItal Microscopy Versus Conventional Frozen Section Diagnosis for intraOperative Histopathological Evaluation (INVIVO)
With the appliance of the in-vivo microscopy after Fluorescein staining, the investigators hypothesize that the preliminary in-vivo histopathological diagnostic accuracy is not inferior to conventional frozen section analysis accuracy when using the final histopathological result as gold standard.
Read the detailed description
In neurosurgery, intraoperative histopathological frozen section analysis (cryosection) offers a crucial tool for the rapid assessment of tumor entity and dignity and the creation of tumor-free resection margins. The method, however, remains unreliable and time-consuming, sometimes prolonging surgical times and demonstrating diagnostic accuracy for frozen section in glioma ranging from 78.4% to 95% in comparison to the final histopathology, depending on the technique used.2,3 To combat these shortcomings, another promising adjunct was developed in the form of intraoperative dye-dependent in-vivo microscopy, for which there has been little scientific evidence so far, with only a few recent studies exploring its utility, safety and general applicability. The theoretical idea of the technique in principle is to allow for histopathological assessment of tumor tissue in-vivo without the need for time-consuming fixation and transport of resected tissue biopsies, aiming for a so-called in-situ digital biopsy and thereby substantially improving operative precision and surgical times. It stands to reason that the benefit in visualization provided by fluorescein staining may further be driven through in-vivo microscopy. Altogether, with the use of fluorescein sodium in in-vivo microscopy, the operating surgeon may in the future inspect supposedly malignant fluorescent tissue first-hand, evaluate it for tumorous cells in real-time and adjust their resection strategy in a far more immediate fashion.
- Conditions
- Intracranial Tumor
- Being tested
- Alcon
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlconDrug
Also called Fluorescein sodium
Fluorescein sodium is administered intravenously with a bolus injection of 5 mg per kg of bodyweight 20-40 minutes prior to the planned tumor resection.
| Study group | Role | What they receive |
|---|---|---|
| Fluorescein sodium | Experimental | A single dose of fluorescein sodium is applied before brain tumor resection. 20-40 minutes prior to the planned tumor resection, a bolus of 5 mg per kg body weight is administered intravenously, staining tumor tissue with fluorescent dye to visualize tumor cells. Receives: Drug: Alcon |
What is being measured
The primary outcome is the main question the study is designed to answer.
Significance: The diagnostic accuracies of the individual methods used for preliminary intraoperative histopathological diagnosis (D1:fluorescein sodium with in-vivo microscopy versus D2: preliminary frozen section assessment)
The primary objective of the clinical trial is to compare the significance of intravenously applied fluorescein as staining agent for assessment of brain tissue texture via in-vivo confocal microscopy with the conventional intraoperative histological frozen section analysis of identical brain tissue samples in the same patient. Both methods will be compared in terms of their accuracy using the standard of practice, the final pathological diagnosis (immunochemistry/molecular pathology).
Measured: 14 days
Secondary outcomes (2)
Incidence of adverse events during surgery and until end of follow-up period (Safety Assessment)
To assess the safety of the Investigational Medicinal Product (IMP) as staining agent for in-vivo confocal microscopy by documentation of adverse events during surgery and until end of follow-up period.
Measured: 24 days
Analysis of surgical time span (comparison of the time span to conduct the assessment of brain tissue texture with fluorescein intervention with the time span to conduct assessment of conventional intraoperative frozen section intervention.
Analysis of surgical time span: comparison of the time span to conduct the assessment of brain tissue texture with fluorescein intervention with the time span to conduct assessment of conventional intraoperative frozen section intervention.
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2020
- Study start30 Dec 2020
- Primary completion17 Jun 2022
- Study completion3 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intracranial TumorStudies of the same condition, open and under way.
- More trials run by Technical University of MunichThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 210 participants (actual)
Sponsor and investigators
- Lead sponsor
- Technical University of Munich
- Sponsor type
- University, hospital or other
- Collaborators
- Carl Zeiss Meditec AG
- Responsible party
- Sponsor
- Investigators
- Jens PD Gempt, MD, Study chair, Technische Universität München, Klinik und Poliklinik für Neurochirurgie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04597801
- Sponsor's protocol ID
- INV-GEM-0200-I
- Acronym
- INVIVO
- Status last verified
- Apr 2022
- First submitted
- 14 Sep 2020
- Last updated
- 10 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPDs will not be shared
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Fluorescein-INtra-VItal Microscopy Versus Conventional Frozen Section Diagnosis for intraOperative Histopathological Evaluation (INVIVO)
- ClinicalTrials.gov ID
- NCT04597801
- Acronym / sponsor ID
- INVIVO / INV-GEM-0200-I
- Conditions
- Intracranial Tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 210 participants (actual)
- Lead sponsor
- Technical University of MunichUniversity, hospital or other
- Collaborators
- Carl Zeiss Meditec AG
- Study start
- 30 Dec 2020 (actual)
- Primary completion
- 17 Jun 2022 (actual)
- Study completion
- 3 Aug 2022 (actual)
- First posted
- 22 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
With the appliance of the in-vivo microscopy after Fluorescein staining, the investigators hypothesize that the preliminary in-vivo histopathological diagnostic accuracy is not inferior to conventional frozen section analysis accuracy when using the final histopathological result as gold standard.
Detailed description
In neurosurgery, intraoperative histopathological frozen section analysis (cryosection) offers a crucial tool for the rapid assessment of tumor entity and dignity and the creation of tumor-free resection margins. The method, however, remains unreliable and time-consuming, sometimes prolonging surgical times and demonstrating diagnostic accuracy for frozen section in glioma ranging from 78.4% to 95% in comparison to the final histopathology, depending on the technique used.2,3 To combat these shortcomings, another promising adjunct was developed in the form of intraoperative dye-dependent in-vivo microscopy, for which there has been little scientific evidence so far, with only a few recent studies exploring its utility, safety and general applicability. The theoretical idea of the technique in principle is to allow for histopathological assessment of tumor tissue in-vivo without the need for time-consuming fixation and transport of resected tissue biopsies, aiming for a so-called in-situ digital biopsy and thereby substantially improving operative precision and surgical times. It stands to reason that the benefit in visualization provided by fluorescein staining may further be driven through in-vivo microscopy. Altogether, with the use of fluorescein sodium in in-vivo microscopy, the operating surgeon may in the future inspect supposedly malignant fluorescent tissue first-hand, evaluate it for tumorous cells in real-time and adjust their resection strategy in a far more immediate fashion.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Fluorescein sodium | Experimental | Drug: AlconA single dose of fluorescein sodium is applied before brain tumor resection. 20-40 minutes prior to the planned tumor resection, a bolus of 5 mg per kg body weight is administered intravenously, staining tumor tissue with fluorescent dye to visualize tumor cells. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age ≥18 years
- Signed informed consent
- Suspected intracranial tumor revealed by cranial magnetic resonance imaging (according to clinical routine) scheduled for resection with intraoperative frozen section evaluation
Key exclusion criteria (8 listed)
- Known allergic or suspected allergic reactions to fluorescein sodium
- Liver disease, CHILD B or C
- Patients under medication with beta-blockers, digoxin, chinidin and probenecid as well as inhibitors of glucuronidation, such as immunosuppressants, when the medication must not be discontinued perioperatively
- Patients with relevant congenital limitations of glucuronidation performance (e.g. Rotor syndrome, Gilbert-Meulengracht syndrome, Crigler-Najjar syndrome)
- Patients with terminal renal failure requiring hemodialysis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlconAlso: Fluorescein sodiumFluorescein sodium is administered intravenously with a bolus injection of 5 mg per kg of bodyweight 20-40 minutes prior to the planned tumor resection. | Drug | Fluorescein sodium |
Primary outcome
Significance: The diagnostic accuracies of the individual methods used for preliminary intraoperative histopathological diagnosis (D1:fluorescein sodium with in-vivo microscopy versus D2: preliminary frozen section assessment)
Time frame: 14 days
The primary objective of the clinical trial is to compare the significance of intravenously applied fluorescein as staining agent for assessment of brain tissue texture via in-vivo confocal microscopy with the conventional intraoperative histological frozen section analysis of identical brain tissue samples in the same patient. Both methods will be compared in terms of their accuracy using the standard of practice, the final pathological diagnosis (immunochemistry/molecular pathology).
2 secondary outcomes
Incidence of adverse events during surgery and until end of follow-up period (Safety Assessment)
Time frame: 24 days
Analysis of surgical time span (comparison of the time span to conduct the assessment of brain tissue texture with fluorescein intervention with the time span to conduct assessment of conventional intraoperative frozen section intervention.
Time frame: 14 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2022.
- Individual participant dataSharing planned: No. IPDs will not be shared
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jens PD Gempt, MD study chair
Technische Universität München, Klinik und Poliklinik für Neurochirurgie
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Alcon in people with Intracranial Tumor, run by Technical University of Munich at 3 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Significance: The diagnostic accuracies of the individual methods used for preliminary intraoperative histopathological diagnosis (D1:fluorescein sodium with in-vivo microscopy versus D2: preliminary frozen section assessment) (time frame: 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Nov 2022.