Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Esophageal Neoplasms

Barrett Esophagus

Gastrointestinal Diseases

Esophageal Diseases

Precancerous Conditions

Esophageal Cancer

* IV-administration of EMI-137: all patients will receive 0.13 mg/kg of the fluorescent tracer EMI-137 intravenously.
* Molecular Fluorescence Endoscopy: approximately 2,5 hours after tracer administration, Molecular Fluorescence Endoscopy will be performed with additional measurements of fluorescence signals.

Intravenous administration of 0.13 mg/kg of the fluorescent tracer EMI-137 approximately 2.5 hours prior to the endoscopy procedure.

IV-administation of EMI-137

A flexible fluorescence fiber-bundle is attached to a fluorescence camera platform to enable the detection of fluorescence signals. The fluorescence fiber-probe is inserted through the standard working-channel of the standard clinical endoscope. Fluorescence imaging will be performed prior to and post the endoscopic resection, during the same endoscopy procedure.

Molecular Fluorescence Endoscopy platform

W.B. Nagengast, MD, PhD, PharmD

G.M. van Dam, MD, PhD

To improve detection of esophageal (pre)malignant lesions during surveillance endoscopy of patients at risk of developing malignancies, for example in Barrett's Esophagus (BE), there is a need for better endoscopic visualization and the ability for targeted biopsies. Optical molecular imaging of neoplasia associated biomarkers could form a promising technique to accommodate this need. It is known that the biomarker c-Met is overexpressed in dysplastic and neoplastic areas in BE segments versus normal tissue and has proven to be a valid target for molecular imaging.

Edinburgh Molecular Imaging Ltd (EMI) has developed a fluorescent tracer specifically targeting c-Met by labeling a small peptide to a fluorescent fluorophore: 'EMI-137'. The investigators hypothesize that when EMI-137 is administered intravenously, it accumulates in c-Met expressing high grade dysplasia (HGD) and esophageal adenocarcinoma (EAC), enabling (early) cancer visualization using a newly developed fluorescent fiber-bundle. This hypothesis will be tested in the current pilot intervention study.

Molecular Fluorescence Endoscopy of (Pre)Malignant Esophageal Lesions

Molecular Fluorescence Endoscopy for the Detection of (Pre)Malignant Lesions in Barrett's Esophagus Using a Fluorescent Tracer 'EMI-137' Targeting c-Met: a Single-center Feasibility and Safety Study

Calculation of the in vivo tumor-to-background ratio (\> 1.5) based on fluorescence intensities in (pre)malignant lesions compared to surrounding healthy esophageal tissue.

University Medical Center Groningen

Carcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Bevacizumab

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

A non-randomized, non-blinded, prospective, feasibility study.

* IV-administration of 4.5 mg of the fluorescent tracer bevacizumab-800CW to a total of 5 patients with locally advanced esophageal cancer. The optimal dose will be expanded to include 30 patients.
* Molecular fluorescence endoscopy: 2-3 days after administration, molecular fluorescence endoscopy will be performed with additional measurements of fluorescence signals.

A non-randomized, non-blinded, prospective, feasibility study.

* IV-administration of 10 mg of the fluorescent tracer bevacizumab-800CW to a total of 3 patients with locally advanced esophageal cancer. The optimal dose will be expanded to include 30 patients.
* Molecular fluorescence endoscopy: 2-3 days after administration, molecular fluorescence endoscopy will be performed with additional measurements of fluorescence signals.

A non-randomized, non-blinded, prospective, feasibility study.

* IV-administration of 25 mg of the fluorescent tracer bevacizumab-800CW to a total of 3 patients with locally advanced esophageal cancer. The optimal dose will be expanded to include 30 patients.
* Molecular fluorescence endoscopy: 2-3 days after administration, molecular fluorescence endoscopy will be performed with additional measurements of fluorescence signals.

Intravenous administration of 4.5, 10 or 25 mg of Bevacizumab-IRDye800CW prior to the endoscopic procedure

Bevacizumab-IRDye800CW

A flexible fluorescence fiber-bundle is attached to a fluorescence camera platform to enable the detection of fluorescence signals. The fluorescence fiber-probe is inserted through the standard working channel of the standard clinical endoscope. Fluorescence imaging will be performed prior to and post the chemoradiotherapy.

W. B. Nagengast, MD, PhD, PharmD

G. M. van Dam, MD, PhD

For locally advanced esophageal cancer (EC), neoadjuvant chemoradiotherapy (nCRT) for 5 weeks followed by esophagectomy and lymphadenectomy, if necessary, is standard of care. It is reported that the pathological complete response (pCR) rate after nCRT ranges from 16% to 43%, with a median of 26.5%. According to current clinical guidelines, patients who achieved pCR still go for surgery even though those patients who achieved pCR may not benefit from surgery. Besides, about 50% of EC patients may have post-operative complications including pneumonia, anastomotic leakage, recurrent laryngeal nerve paralysis, which lead to low health-related quality of life (HQoL).

The golden standard to test the pathological response is by pathological assessment of the surgical specimen and thus after surgery. Theoretically, if pCR after nCRT can be predicted accurately before surgery by advanced imaging techniques, patients could have a wait-and-see. The wait-and-see procedure includes regular follow-up and salvage surgery if recurrence is present. Therefore, molecular fluorescence endoscopy (FME) using near-infrared fluorescence (NIRF) tracer bevacizumab-800CW targeting vascular endothelial growth factor combined with high-definition white light (HD-WL) endoscopy is expected to be a promising technique to monitor pCR and fill the gap.

Fluorescence Endoscopy of Esophageal Carcinoma

Fluorescence Molecular Endoscopy of Locally Advanced Esophageal Carcinoma Using Bevacizumab-800CW to Evaluate Dose Response After Neoadjuvant Chemoradiotherapy: a Single-center Feasibility Study.

To determine the sensitivity of the marker bevacizumab-800CW in discriminating between tumorous and non-tumorous tissue prior to and post neoadjuvant chemoradiotherapy, to identify patients who benefit from the chemoradiotherapy.

Monitoring vital signs (blood pressure, heart frequency and temperature) and/or (serious) adverse events that are related to the administration of bevacizumab-800CW

Correlate the H/E images to the fluorescent images made with multiple ex vivo imaging modalities.

Multi-diameter single-fiber reflectance with single-fiber fluorescence (MDSFR/SFF) spectroscopy can measure the fluorescence signal quantitatively, both in vivo and ex vivo.

CLE is a confocal laser endomicroscopy system which enables in vivo microscopic images of the tissue

Imaging of the distribution of bevacizumab-800CW with a fluorescence microscoop.

Both the images and specific measurements are used to calculate the fluorescence intensity (TBR \& intrinsic fluorescence) and a difference between the before and after intensity is calculated.

Nervous System Diseases

Gland and Hormone Related Diseases

Adenoma

Pituitary Diseases

Neuroendocrine Tumors

Pituitary Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Hypothalamic Diseases

Brain Diseases

Central Nervous System Diseases

Endocrine System Diseases

Endocrine Gland Neoplasms

Hypothalamic Neoplasms

Supratentorial Neoplasms

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Neuroendocrine Tumor

IV-administration of 4.5 mg of the fluorescent tracer bevacizumab-800CW to 3 patients with a pituitary neuroendocrine tumor (PitNET) with a Knosp grade of 3 or 4. The optimal dose will be expanded to include 6 patients.

IV-administration of 10 mg of the fluorescent tracer bevacizumab-800CW to 3 patients with a pituitary neuroendocrine tumor (PitNET) with a Knosp grade of 3 or 4. The optimal dose will be expanded to include 6 patients.

IV-administration of 25 mg of the fluorescent tracer bevacizumab-800CW to 3 patients with a pituitary neuroendocrine tumor (PitNET) with a Knosp grade of 3 or 4. The optimal dose will be expanded to include 6 patients.

Intravenous administration of 4.5, 10 or 25 mg of Bevacizumab-IRDye800CW prior to endoscopic transsphenoidal surgery

A flexible fluorescence fiber-bundle is attached to a fluorescence camera platform to enable the detection of fluorescence signals. The fluorescence fiber-probe is inserted through the standard working channel of the Surgvision explorer endoscope. During surgery, three imaging moments are defined in which the fluorescence molecular endoscopy system will detect the fluorescent signal

There is a need for improved visualization of presence and extent of pituitary neuroendocrine tumor (PitNET) tissue during transsphenoidal surgery (TSS), especially in tumors invading the cavernous sinus (CS). Optical molecular imaging of PitNET associated biomarkers is a promising technique to accommodate this need. Vascular Endothelial Growth Factor (VEGF-A) is overexpressed in PitNET tissue compared to normal pituitary tissue and has proven to be a valid target for molecular imaging. Bevacizumab is an antibody that binds VEGF-A. By conjugating a fluorescent dye to this antibody, the fluorescent tracer molecule bevacizumab-800CW is created, which binds to VEGF-A. The investigators hypothesize that bevacizumab-800CW accumulates in PitNET tissue, enabling visualization using a molecular fluorescence endoscopy system. In this pilot intervention study the investigators will determine the feasibility of using microdoses (4.5, 10 and 25 mg) of bevacizumab-800CW to detect PitNET tissue intraoperatively.

The study is a non-randomized, non-blinded, prospective, single center, pilot dose-finding study.

Detection of PitNET Tissue During TSS Using Bevacizumab-800CW

Detection of Pituitary Neuroendocrine Tumor (PitNET) Tissue During Endoscopic Transsphenoidal Surgery Using Bevacizumab-800CW

To determine the sensitivity of the marker bevacizumab-800CW in discriminating between tumorous and non-tumorous tissue during endoscopic transsphenoidal surgery of pituitary neuroendocrine tumors (PitNETs) defined as the tumor to background ratio and intrinsic fluorescence

Data collection as a measure of safety and tolerability regarding administration of bevacizumab-800CW

Correlate the H/E images to the fluorescent images made with multiple ex vivo imaging modalities

Multi-diameter single-fiber reflectance with single-fiber fluorescence (MDSFR/SFF) spectroscopy can measure the fluorescence signal quantitatively, both in vivo and ex vivo

Imaging of the distribution of bevacizumab-800CW with a fluorescence microscope

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Molecular Fluorescence Endoscopy of (Pre)Malignant Esophageal Lesions	NCT03205501	Barrett Esophag... Esophageal Canc... Dysplasia in Ba...	IV-administatio... Molecular Fluor...	18 Years -	University Medical Center Groningen
Molecular Fluorescence Endoscopy of (Pre)Malignant Esophageal Lesions	NCT03205501	Barrett Esophag... Esophageal Canc... Dysplasia in Ba...	IV-administatio... Molecular Fluor...	18 Years -	University Medical Center Groningen
Fluorescence Endoscopy of Esophageal Carcinoma	NCT03558724	Esophageal Canc...	Bevacizumab-IRD... Molecular Fluor...	18 Years -	University Medical Center Groningen
Fluorescence Endoscopy of Esophageal Carcinoma	NCT03558724	Esophageal Canc...	Bevacizumab-IRD... Molecular Fluor...	18 Years -	University Medical Center Groningen
Detection of PitNET Tissue During TSS Using Bevacizumab-800CW	NCT04212793	Pituitary Tumor Pituitary Adeno... Pituitary Macro...	Bevacizumab-IRD... Molecular Fluor...	18 Years -	University Medical Center Groningen
Molecular Fluorescence Endoscopy of (Pre)Malignant Esophageal Lesions	NCT03205501	Barrett Esophag... Esophageal Canc... Dysplasia in Ba...	IV-administatio... Molecular Fluor...	18 Years -	University Medical Center Groningen

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