Clinical trial NCT03558724: Fluorescence Endoscopy of Esophageal Carcinoma
Official title: Fluorescence Molecular Endoscopy of Locally Advanced Esophageal Carcinoma Using Bevacizumab-800CW to Evaluate Dose Response After Neoadjuvant Chemoradiotherapy: a Single-center Feasibility Study.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Esophageal Cancer
Keywords: Fluorescence
Endoscopy
Bevacizumab-800CW
Locally advanced esophageal cancer
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2018-06-15
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed description: See brief summary

Eligibility criteria: Inclusion Criteria:

* Locally advanced esophageal carcinoma (cT1b-4a N0-3 M0) in multi-disciplinary esophageal oncology meeting agreed on long course neoadjuvant chemoradiotherapy, followed by esophagectomy;
* Age ≥ 18 years;
* Written informed consent.

Exclusion Criteria:

* Patients with psychological diseases or medical issues who are not able to sign informed consent form;

  * Concurrent uncontrolled medical conditions;
  * Pregnancy or breast feeding. A negative pregnancy test must be available for women of childbearing potential (i.e. premenopausal women with intact reproductive organs and women less than two years after menopause);
  * Irradical endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) of primary tumor prior to start of neoadjuvant chemoradiotherapy
  * Received a different investigational drug within 30 days prior to the dose of bevacizumab-800CW;
  * History of infusion reactions to bevacizumab or other monoclonal antibodies;

Primary outcomes:
measure: Discrimination of tumorous and non-tumorous tissue based on in vivo and ex vivo fluorescence measurements from bevacizumab-800CW gained during fluorescence endoscopy procedure
timeFrame: Three days after tracer injection
measure: Safety of bevacizumab-800CW administration by monitoring vital signs and/or (serious) adverse events.
timeFrame: Up to 14 days after tracer injection
Secondary outcomes:
measure: The correlation of in vivo and ex vivo fluorescent signals to histopathological analysis results
timeFrame: Up to 1,5 year
measure: Quantification of the fluorescent signal by MDSFR/SFF spectroscopy
timeFrame: Up to 1,5 year
measure: To localization and distribution of bevacizumab-800CW fluorescent signal at cell level observed in vivo by confocal laser endomicroscopy (CLE)
timeFrame: Up to 1,5 year
measure: Assessment of the (sub)-cellular distribution of bevacizumab-800CW by ex vivo fluorescence microscopy
timeFrame: Up to 1,5 year
measure: The variation in fluorescence intensity between fluorescence molecular endoscopy before and after neoadjuvant chemoradiotherapy defined as the tumor to background ratio and intrinsic fluorescence.
timeFrame: Up to 1,5 year
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: University Medical Center Groningen
name: W. B. Nagengast, MD, PhD, PharmD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Center Groningen
name: G. M. van Dam, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Duan XF, Tang P, Yu ZT. Neoadjuvant chemoradiotherapy for resectable esophageal cancer: an in-depth study of randomized controlled trials and literature review. Cancer Biol Med. 2014 Sep;11(3):191-201. doi: 10.7497/j.issn.2095-3941.2014.03.005.
citation: Booka E, Takeuchi H, Nishi T, Matsuda S, Kaburagi T, Fukuda K, Nakamura R, Takahashi T, Wada N, Kawakubo H, Omori T, Kitagawa Y. The Impact of Postoperative Complications on Survivals After Esophagectomy for Esophageal Cancer. Medicine (Baltimore). 2015 Aug;94(33):e1369. doi: 10.1097/MD.0000000000001369.
citation: Raymond D. Complications of esophagectomy. Surg Clin North Am. 2012 Oct;92(5):1299-313. doi: 10.1016/j.suc.2012.07.007.