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

NCT02113202 | Completed Phase 1 DMC

• 2 other identifiers: NL45148.042.132013-002490-22
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Adenomatous Polyposis Coli

Keywords

Optical imaging; Fluorescence endoscopy; Near infrared fluorescence; Familial Adenomatous Polyposis; IRDye800CW; Vascular Endothelial Growth Factor A; Gastrointestinal endoscopy

Outcome Measures

Primary Outcomes (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.

  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).

  At surveillance endoscopy

Secondary Outcomes (3)

• Meassure the mean fluorescent intensity of the polyps during fluorescence endoscopy, resect the polyps and score VEGF intensity after immunohistochemistry for VEGF.

  Two years

• Number of participants with Serious Adverse Events as a measure of safety and Tolerability.

  Up to 1 week after administration

• 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.

  Two years

Study Arms (3)

Tracer dose: 4.5 mg

EXPERIMENTAL

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; Device: Near infrared fluorescence endoscopy platform

Tracer dose: 10 mg

EXPERIMENTAL

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; Device: Near infrared fluorescence endoscopy platform

Tracer dose: 25 mg

EXPERIMENTAL

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; Device: Near infrared fluorescence endoscopy platform

Interventions

Bevacizumab-IRDye800CW DRUG

Intravenous administration of a 4.5 mg, 10 mg or 25 mg of Bevacizumab-IRDye800CW 3 days prior to the fluorescence endoscopy procedure.

Also known as: Beva-800CW, Bevacizumab-800CW, Avastin-800CW (Roche)

Tracer dose: 10 mg; Tracer dose: 25 mg; Tracer dose: 4.5 mg

Near infrared fluorescence endoscopy platform DEVICE

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.

Tracer dose: 10 mg; Tracer dose: 25 mg; Tracer dose: 4.5 mg

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

MeSH Terms

Conditions

Adenomatous Polyposis Coli

Condition Hierarchy (Ancestors)

Adenomatous Polyps; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Polyposis; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2014
• First Posted: April 14, 2014
• Study Start: March 1, 2014
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: October 27, 2023

Record last verified: 2023-10

Locations

NL (1)