Clinical trial NCT06292845: Ex Vivo Tumor Visualization and Resection Margin Assessment Using Topically Applied Fluorescent Imaging Agents
Official title: Ex Vivo Tumor Visualization and Resection Margin Assessment Using Topically Applied Fluorescent Imaging Agents
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Solid Tumor, Adult
Keywords: Fluorescence imaging
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
First posted: 2024-03-05
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: This is a proof-of-principle study, that uses freshly resected human solid tumor specimens to assess the performance of topically applied fluorescent imaging agents for the detection of tumor tissue and close / tumor-positive resection margins ex vivo. Surgery will be performed in conformity with hospital protocol. The study will not interfere with the standard clinical care.

Detailed description: Surgical excision remains an integral part of curative-intent treatment for most solid tumors. The goal of surgical resection is to completely remove all tumor tissue. A tumor-positive or inadequate surgical resection margin, defined as cancer cells at or near (depending on tumor type) the edge of the resection specimen, has major prognostic implications and often necessitates additional treatments. These additional treatments are in turn associated with increased morbidity, complication risks, and healthcare costs.

To achieve a complete resection of the tumor, surgeons rely on visual inspection and palpation, sometimes assisted by localization or pathology techniques such as implanted (radioactive/magnetic) seeds and frozen section analysis. However, inadequate resection margin rates in solid tumors remain high, indicating current methods for intraoperative margin assessment are insufficient. They lack real-time feedback on the margin status of large tissue surface areas to guide additional resection.

A technique that could meet these requirements is tumor-targeted fluorescence imaging (FI). It combines the administration of a fluorescence imaging agent with the use of fluorescence light. This technique allows for real-time optical feedback by selectively highlighting tumor tissue that expresses certain molecular targets that bind the imaging agent or has certain characteristics that activate it.

Presently, the vast majority of fluorescence imaging agents under investigation for intraoperative tumor visualization and resection margin assessment have to be administered intravenously, hours or days prior to surgery. Very recently, new imaging agents have been designed that can be topically administered. Topically applied imaging agents allow for specimen-based (ex vivo) resection-margin assessment using FI, without the necessity to administer the probe to the patient. This approach offers several advantages: (I) ex vivo topical application on the resected specimen eliminates all toxicity risks, as the patient is not exposed to the imaging agent; (II) it is much more cost-effective. First of all, a lower imaging agent dose can be used because there is no systemic volume of distribution, and the probe is not metabolized and excreted. Secondly, toxicity testing and in-patient clinical trials are not required to use the ex vivo topical approach in clinical practice, which greatly reduces implementation time and costs; (III) the ex vivo topical approach is easier to implement in the current surgical workflow, and does not require the patient logistics needed for systemic administration.

In this proof-of-principle study, the investigators will investigate if topically applied fluorescent imaging agents can be used to visualize tumor tissue and detect inadequate resection margins ex vivo on freshly resected solid human tumors.

Eligibility criteria: Inclusion Criteria:

1. Patients with a biopsy-proven solid tumor, scheduled for surgery at the Erasmus Medical Center.
2. Signed and dated informed consent obtained before any study-related procedure is performed.

Exclusion Criteria:

1. Terminated surgical procedure.
2. No fresh specimen available.
3. Participation in a clinical trial for which the patient receives another fluorophore perioperatively.

Primary outcomes:
measure: Tumor-to-background ratio (TBR) of the fluorescence signal on the resection specimen surface and on 3-5 mm thick tissue slices.
timeFrame: through study completion, up to 3 years
Secondary outcomes:
measure: Imaging agent fluorescence signal intensity on close / tumor-positive resection planes compared with (wide) tumor-negative resection planes, as confirmed by histopathology
timeFrame: through study completion, up to 3 years
measure: Difference in tumor-to-background ratio (TBR) between different imaging time windows
timeFrame: through study completion, up to 3 years
measure: The concordance between the presence of tumor cells and fluorescence signal
timeFrame: through study completion, up to 3 years
measure: Depth of the fluorescence signal on 4-μm tissue slides
timeFrame: through study completion, up to 3 years
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: Erasmus University Medical Center
state: Zuid-Holland
Study officials:
References: