Visualization of Rectal Cancer During Endoscopy, Using a Fluorescent Tracer (RAPIDO-TRACT)
Device: NIR fluorescence endoscopy
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||Visualization of a VEGF-targeted Optical Fluorescent Imaging Tracer in Rectal Cancer During Flexible NIR Fluorescence Endoscopy|
- Sensitivity of the marker bevacizumab-IRDye800CW [ Time Frame: First endoscopic procedure before start radio-chemotherapy and second endoscopic procedure 3 weeks after start of radiochemotherapy ] [ Designated as safety issue: No ]
To determine the sensitivity of the marker bevacizumab-IRDye800CW measured by innovative molecular imaging flexible NIR fluorescence endoscopy, and optionally optoacoustic endoscopy, in identifying target expression and heterogeneity prior to the start, or during early treatment, of neoadjuvant radiochemotherapy, to identify patients who benefit from additional treatment targeting VEGF to increase pCR in future studies.
Research aim to assess primary objectives by evaluation of biopsy specimen:
- To assess accumulation of bevacizumab-IRDye800CW in rectal cancer tissue and surrounding tissue at baseline and following radiochemotherapy of patients included in the RAPIDO trial.
- Evaluation of tumor areas with high fluorescence and low fluorescence signal.
- To correlate the above to VEGF-levels determined by immuno-histochemistry.
- Correlation between bevacizumab-IRDye800CW uptake and pathological response (pCR) [ Time Frame: Endoscopic procedures before and after chemoradiation therapy, assesing of pathological respons after churgical intervention ] [ Designated as safety issue: No ]
- In vivo quantification of the NIR fluorescent signal of bevacizumab-IRDye800CW using the NIR fluorescence endoscope vs. ex vivo VEGF levels in biopsies [ Time Frame: Before start and after chemoradiation therapy ] [ Designated as safety issue: No ]
- To Perform correlate pathways analyses using RNA/DNA/protein analyses to NIR fluorescence data [ Time Frame: After surgery ] [ Designated as safety issue: No ]
- The ability of optoacoustic endoscopy to detect bevacizumab-IRDye800CW in deeper areas of the tumor [ Time Frame: Before start and after chemoradiation therapy ] [ Designated as safety issue: No ]
- Collection of safety regarding administration of Bevacizumab-IRDye800CW [ Time Frame: Participants will be followed the duration of the chemoradiation therapy till surgery ] [ Designated as safety issue: Yes ]To abtain information on safety aspectsof the tracer, side effects, adverse events (AE), serious adverse events (SAE) and suspected unexpected serious adverse reactions (SUSAR)
|Study Start Date:||October 2013|
|Estimated Study Completion Date:||January 2017|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Experimental: NIR endoscopy with Bevacizumab-IRDye800CW
In this non-randomized, non-blinded, prospective, feasibility study, bevacizumab-IRDye800CW will be administered to a total of 30 patients with proven locally advanced rectal cancer.
Intravenous administration of a microdose (4.5mg, subtherapeutic) of Bevacizumab-IRDye800CW prior to the endoscopic procedure
Other Names:Device: NIR fluorescence endoscopy
48-72 hours administration of Bevacizumab-IRDye800CW a flexible NIR fluorescence endoscopy will be performed via the rectum
Other Name: Sigmoid endoscopy using near infrared fluorescence
In this non-randomized, non-blinded, prospective, single center feasibility study, patients with locally advanced rectal cancer who are included in the RAPIDO study (NL36315.042.11) will undergo two times epi-illumination endoscopy (in other words flexible NIR fluorescence endoscopy).
The study consists of a total of five study procedure related visits:
- Visit 1: During a screening visit, eligibility will be evaluated and patient characteristics will be collected.
- Visit 2: During the second visit 4.5 mg of bevacizumab-IRDye800CW will be administered intravenously. The patient will then be observed for 1 hour post administration.
- Visit 3: First endoscopy will be performed at baseline (two days after tracer administration); before the start of chemoradiotherapy.
- Visit 4: After chemoradiotherapy patients will receive a second dose of 4.5 mg of bevacizumab-IRDye800CW (second tracer administration)
- Visit 5: A second flexible NIR fluorescence endoscopy procedure will be performed (two-three days after the second tracer injection), preferably right before surgery.
Optionally and when available, we will ask patients if they would like to undergo optoacoustic endoscopy. This is a form of endoscopic ultrasound which is able to detect bevacizumab-IRDye800CW up to 2 cm in depth. The procedure is comparable with NIR fluorescence endoscopy. If patients agree, after removal of the NIR fluorescence endoscope the optoacoustic endoscope will be introduced in the rectum of the patient for detection of bevacizumab-IRDye800CW in deeper areas of the tumor.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01972373
|Contact: Wouter B Nagengast, MD, PhD||+31 (0)50 email@example.com|
|Contact: Jolien JJ Tjalma, MD||+31 (0)50 firstname.lastname@example.org|
|University Medical Centre Groningen||Recruiting|
|Groningen, Netherlands, 9713 GZ|
|Contact: Wouter B Nagengast, MD, PhD +3150-3615755 email@example.com|
|Contact: Jolien JJ Tjalma, MD +3150-3610030 firstname.lastname@example.org|
|Sub-Investigator: Jolien JJ Tjalma, MD|
|Principal Investigator:||Wouter B Nagengast, MD, PhD||University Medical Center Groningen|
|Principal Investigator:||Geke AP Hospers, Prof. dr.||University Medical Center Groningen|
|Principal Investigator:||Boudewijn v. Etten, MD, PhD||University Medical Center Groningen|