Clinical trial NCT05498051: Fluorescent Sentinel Lymph Node Identification in Colon Carcinoma Using Submucosal Bevacizumab-800CW.
Official title: A Pilot Study to Assess the Safety and Feasibility of Fluorescent Sentinel Lymph Node Identification in Colon Carcinoma Using Submucosal Bevacizumab-800CW.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Colonic Neoplasms
Sentinel Lymph Node
Fluorescence
Colorectal Neoplasms
Keywords: Sentinel lymph node
Colon cancer
Fluorescence
bevacizumab-800CW
bevacizumab-IRdye
Lead sponsor: Meander Medical Center
Sponsor class: OTHER
First posted: 2022-08-11
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a single-centre, open-label, non-randomized cohort safety and feasibility study.
Primary purpose: TREATMENT

Brief summary: This prospective study aims to assess the safety and feasibility of lymph node identification using bevacizumab-800CW in patients with cT1-3N0-2 tumours, using peritumoral submucosal injections

Detailed description: The current gold standard for the treatment of colon carcinoma consists of the surgical en-bloc resection of the colonic segment including the adjacent mesocolon containing the draining lymph nodes. Analysis of these lymph nodes is important, since lymph node status is one of the most important prognostic factors determining the use of adjuvant chemotherapy. Although patients with tumour stage I and II do not have lymph node metastases, 15-20% develop recurrent disease. Several studies suggest that ultrastaging techniques such as immunohistochemistry (IHC) or reverse transcriptase polymerase chain reaction (RT-PCR) using multilevel slicing results in upstaging of 14-18% of patients, due to newly found (micro)metastasis. Furthermore, several studies indicate that these micrometastases are correlated with a significantly poorer prognosis, subsequently suggesting that this subgroup of patients might benefit of adjuvant chemotherapy. Therefore, the most recent Dutch guidelines advice the use of adjuvant chemotherapy in this "upstaged" group, although evidence is still lacking.

However, ultrastaging techniques are labour-intensive and costly, and therefore not suitable for analyses of all lymph nodes that have been collected during segmental colectomy. Sentinel lymph node (SLN) identification in colon carcinoma has been proposed to overcome this problem by identifying the first order draining lymph node(s) of the tumour, which have the highest chance of containing metastatic tumour cells. Several studies aimed at SLN identification in colon carcinoma have been published, however, early studies using radio-guided or blue-dye guided SLN identification, showed relatively high rates of false negatives with consequent low sensitivity rates. Since mesocolon is rather fatty tissue, visualization of conventional dyes is difficult. Indocyanine green (ICG), which can be visualized using near infrared (NIR), has been put forward since it is known to penetrate relatively deep into living tissue.

Nevertheless, results of SLN identification using ICG remain unsatisfying with high false-negative rates and low sensitivity. Most likely this is due to the fact that these studies also included large cT3-cT4 tumours and patients with massive lymph node involvement. Which are factors known to interfere with lymph drainage patterns. Furthermore, subserosal injections were frequently used, while it is suggested that submucosal injections might result in better sensitivity of the procedure. In the FLUOR-SLN-ICG pilot study, we successfully conducted SLN identification in patients with ICG.

Recently, more research is conducted in tumour-targeted tracers as they have many advantages compared to ICG. For example, tumour-targeted tracers can be preoperatively administered which aid logistics, binds to tumour and metastases, thus allowing more time for uptake in patients with larger tumours and lymph node metastases. These properties may result in increased accuracy and would be more broadly applicable compared to ICG. Furthermore, tumour-targeted tracers can also be administrated intravenously and potentially identify lymph node metastases without having to perform a colonoscopy. However, administration via colonoscopy of tumour-targeted tracers for the detection of lymph node metastases in colon carcinoma has not been performed yet, and intravenous administration would be a step after administration via colonoscopy.

Therefore this prospective study aims to assess the safety and feasibility of lymph node identification using bevacizumab-800CW in patients with cT1-3N0-2 tumours, using peritumoral submucosal injections.

Eligibility criteria: Inclusion Criteria:

* Oral and written informed consent (IC)
* Aged 18 years and older
* Patients with pathologically confirmed and/or suspected cT1-3N0-2M0 colon carcinoma.

Exclusion Criteria:

* Distant metastasis
* Suspicion of cT4 disease based on pre-operative assessment
* Metastatic or T4 disease discovered during intraoperative staging
* Pregnancy, lactation or a planned pregnancy during the course of the study
* Previous colon surgery, excluding appendectomy.
* Contra-indication for laparoscopic/robotic surgery
* Inadequately controlled hypertension with or without current antihypertensive medication.
* Within 6 months prior to inclusion: myocardial infarction, TIA, CVA, pulmonary embolism, unstable angina pectoris, or uncontrolled chronic hepatic failure.
* Regarding Bevacizumab: Hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies. Or an allergy for it's components (Trehalose dehydrate, sodium phosphate, polysorbate 20, water for injections)

Primary outcomes:
measure: Identification rate of SLN(s) or lymph node metastases
timeFrame: During surgery
measure: Safety of SLN identification
timeFrame: Measured till 90 days after surgery
Secondary outcomes:
measure: Amount of fluorescence in lymph node metastases compared to lymph node without metastases
timeFrame: 3 months (after fluorescence measurement)
measure: false-negative SLNs
timeFrame: 3 months (after pathological examination)
measure: true-negative SLNs
timeFrame: 3 months (after pathological examination)
measure: sensitivity
timeFrame: 3 months (after pathological examination)
measure: upstaged patients
timeFrame: 3 months (after pathological examination)
measure: aberrant lymph node status
timeFrame: 3 months (after pathological examination)
measure: accuracy
timeFrame: 3 months (after pathological examination)
measure: negative predictive value
timeFrame: 3 months (after pathological examination)
measure: number of SLNs identified
timeFrame: 3 months (after pathological examination)
Other outcomes:
Locations:
city: Amersfoort
country: Netherlands
facility: Meander Medisch Centrum
state: Utrecht
Study officials:
affiliation: Meander Medisch Centrum
name: Esther Consten, prof. dr.
role: PRINCIPAL_INVESTIGATOR
References: