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Molecular Fluorescence Endoscopy in Patients With Familial Adenomatous Polyposis, Using Bevacizumab-IRDye800CW (FLUOFAP)

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ClinicalTrials.gov Identifier: NCT02113202
Recruitment Status : Completed
First Posted : April 14, 2014
Last Update Posted : January 11, 2016
Sponsor:
Information provided by (Responsible Party):
dr. W.B. Nagengast, MD, University Medical Center Groningen

Brief Summary:
There is a need for better visualization of polyps during surveillance endoscopy in patients with hereditary colon cancer syndromes like Familial Adenomatous Polyposis (FAP) and Lynch Syndrome (LS), to improve the adenoma detection rate. Optical molecular imaging of adenoma associated biomarkers is a promising technique to accommodate this need. The biomarker Vascular Endothelial Growth Factor (VEGF) is overexpressed in adenomatous colon tissue versus normal tissue and has proven to be a valid target for molecular imaging. The University Medical Center Groningen (UMCG) developed a fluorescent tracer by labeling the VEGF-targeting humanized monoclonal antibody bevacizumab, currently used in anti-cancer therapy, with the fluorescent dye IRDye800CW. The investigators hypothesize that when bevacizumab-IRDye800CW is administered to patients, it accumulates in VEGF expressing adenomas, enabling adenoma visualization using a newly developed near-infrared (NIR) fluorescence endoscopy platform (NL43407.042.13). This hypothesis will be tested in this feasibility study, next to the determination of the optimal tracer dose.

Condition or disease Intervention/treatment Phase
Adenomatous Polyposis Coli Drug: Bevacizumab-IRDye800CW Device: Near infrared fluorescence endoscopy platform Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Visualization of a VEGF-targeted Near-Infrared Fluorescent Tracer in Patients With Familial Adenomatous Polyposis During Fluorescence Endoscopy A Single Center Pilot Intervention Study
Study Start Date : March 2014
Actual Primary Completion Date : October 2015
Actual Study Completion Date : October 2015


Arm Intervention/treatment
Experimental: Tracer dose: 4.5 mg
Patients receive three days before the fluorescence endoscopy procedure (with the near infrared fluorescence endoscopy platform) 4.5 mg of the fluorescent tracer bevacizumab-IRDye800CW.
Drug: Bevacizumab-IRDye800CW
Intravenous administration of a 4.5 mg, 10 mg or 25 mg of Bevacizumab-IRDye800CW 3 days prior to the fluorescence endoscopy procedure.
Other Names:
  • Beva-800CW
  • Bevacizumab-800CW
  • Avastin-800CW (Roche)
Device: Near infrared fluorescence endoscopy platform
A flexible fiber-bundle is attached with its proximal end to a camera which can detect near infrared fluorescent light. The distal end is inserted into the working channel of a clinical video endoscope, which is used for the surveillance endoscopy procedure.
Experimental: Tracer dose: 10 mg
Patients receive three days before the fluorescence endoscopy procedure (with the near infrared fluorescence endoscopy platform) 10 mg of the fluorescent tracer bevacizumab-IRDye800CW.
Drug: Bevacizumab-IRDye800CW
Intravenous administration of a 4.5 mg, 10 mg or 25 mg of Bevacizumab-IRDye800CW 3 days prior to the fluorescence endoscopy procedure.
Other Names:
  • Beva-800CW
  • Bevacizumab-800CW
  • Avastin-800CW (Roche)
Device: Near infrared fluorescence endoscopy platform
A flexible fiber-bundle is attached with its proximal end to a camera which can detect near infrared fluorescent light. The distal end is inserted into the working channel of a clinical video endoscope, which is used for the surveillance endoscopy procedure.
Experimental: Tracer dose: 25 mg
Patients receive three days before the fluorescence endoscopy procedure (with the near infrared fluorescence endoscopy platform) 25 mg of the fluorescent tracer bevacizumab-IRDye800CW.
Drug: Bevacizumab-IRDye800CW
Intravenous administration of a 4.5 mg, 10 mg or 25 mg of Bevacizumab-IRDye800CW 3 days prior to the fluorescence endoscopy procedure.
Other Names:
  • Beva-800CW
  • Bevacizumab-800CW
  • Avastin-800CW (Roche)
Device: Near infrared fluorescence endoscopy platform
A flexible fiber-bundle is attached with its proximal end to a camera which can detect near infrared fluorescent light. The distal end is inserted into the working channel of a clinical video endoscope, which is used for the surveillance endoscopy procedure.



Primary Outcome Measures :
  1. Number of fluorescent adenomatous polyps during surveillance endoscopy using the near-infrared fluorescence endoscopy platform in patients with Familial Adenomatous Polyposis (FAP), after administration of the fluorescent tracer bevacizumab-IRDye800CW. [ Time Frame: At surveillance endoscopy ]
    The main objective of this study is to determine the sensitivity of the fluorescent tracer bevacizumab-IRDye800CW and the near-infrared fluorescence endoscopy platform in identifying adenomatous polyps during surveillance endoscopy in patients with Familial Adenomatous Polyposis (FAP).


Secondary Outcome Measures :
  1. Meassure the mean fluorescent intensity of the polyps during fluorescence endoscopy, resect the polyps and score VEGF intensity after immunohistochemistry for VEGF. [ Time Frame: Two years ]
    In this outcome meassure, it is determined if there is a correlation between the observed mean fluorescence intensity of a polyp and the VEGF expression in the same polyp, as determined with immunohistochemistry and eventually RNA/DNA analysis. In other words, does the mean fluorescence intensity reflect the VEGF expression of the polyp?

  2. Number of participants with Serious Adverse Events as a measure of safety and Tolerability. [ Time Frame: Up to 1 week after administration ]
    Collection of safety data regarding administration of Bevacizumab-IRDye800CW (adverse events (AE), serious adverse events (SAE) and suspected unexpected serious adverse reactions (SUSAR)).

  3. Measure the mean fluorescent intensity of adenomas and compare this between the three different dosing groups to determine the best tracer dose for the fluorescence endoscopy procedure. [ Time Frame: Two years ]
    The goal of this outcome measure, is to determine the optimal tracer dose (4.5, 10 or 25 mg) of bevacizumab-IRDye800CW for the molecular-guided fluorescence endoscopy procedure to visualize adenomas. The fluorescence intensity of adenomas will be measured in vivo during fluorescence endoscopy and ex vivo (e.g. using confocal fluorescence microscopy, spectroscopy). This will be compared between the three subgroups (patients with different time intervals between tracer injection and endoscopy procedure) to determine the best time interval between tracer injection and endoscopy procedure.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with genetically or clinically proven Familial Adenomatous Polyposis. Genetically proven: Adenomatous Polyposis Coli (APC)-mutation identified. Clinically proven: more than 100 colorectal polyps at diagnosis
  • Age 18 to 70 years
  • Written informed consent
  • Adequate potential for follow-up

Exclusion Criteria:

  • Medical or psychiatric conditions that compromise the patient's ability to give informed consent
  • Proctocolectomy
  • MutYH mutation
  • Concurrent uncontrolled medical conditions
  • Pregnant or lactating women. Documentation of a negative pregnancy test must be available for woman of childbearing potential. Woman of childbearing potential are pre-menopausal women with intact reproductive organs and women less than two years after menopause.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02113202


Locations
Netherlands
University Medical Center Groningen
Groningen, Netherlands, 9713 GZ
Sponsors and Collaborators
University Medical Center Groningen
Investigators
Principal Investigator: Wouter B Nagengast, PharmD MD PhD University Medical Center Groningen
Principal Investigator: Jan Jakob Koornstra, MD PhD University Medical Center Groningen
Principal Investigator: Jan H Kleibeuker, MD, senior full professor University Medical Center Groningen

Responsible Party: dr. W.B. Nagengast, MD, PharmD MD PhD, University Medical Center Groningen
ClinicalTrials.gov Identifier: NCT02113202     History of Changes
Other Study ID Numbers: NL45148.042.13
2013-002490-22 ( EudraCT Number )
First Posted: April 14, 2014    Key Record Dates
Last Update Posted: January 11, 2016
Last Verified: January 2016

Keywords provided by dr. W.B. Nagengast, MD, University Medical Center Groningen:
Optical imaging
Fluorescence endoscopy
Near infrared fluorescence
Familial Adenomatous Polyposis
IRDye800CW
Vascular Endothelial Growth Factor A
Gastrointestinal endoscopy

Additional relevant MeSH terms:
Colorectal Neoplasms
Nasopharyngeal Neoplasms
Adenomatous Polyposis Coli
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Adenomatous Polyps
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplastic Syndromes, Hereditary
Intestinal Polyposis
Genetic Diseases, Inborn
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents