The Correlation of Surgical Colorectal Cancer Specimen Pathology With the Fluorescence of Photodynamic Diagnostics (PDD)

The Correlation of Surgical Colorectal Cancer Specimen Pathology With the Fluorescence of Photodynamic Diagnostics (PDD): a Clinical Pilot Study

This will be a pilot study involving 5 patients diagnosed with colorectal carcinoma and treated with pre-operative chemotherapy and external beam radiation therapy at the Jewish General Hospital, whom will very soon undergo surgery. Participants will be sensitized by the instillation of a 250 mL enema containing 1.6 mmol of HAL. The enema will be administered with a plastic tube with an inflatable blocking balloon to prevent leakage of the enema. Fluorescence sigmoidoscopy will be performed with white light then blue excitation light after retention of the enema for 60 minutes, followed by a rest time of up to 30 minutes before rectoscopy. Red fluorescence should be induced by illumination with blue light. Pictures with and without fluorescence will be taken. The patients will undergo a colectomy (partial or complete) within the next 2-3 days and the surgical specimens will be collected for further fluorescence microscopy studies and pathological correlation of fluoresce with malignant pathology/histology as the gold standard. The total concentration of porphyrins in the patients' urine and serum will be recorded before sensitization, immediately after sensitization (instillation of the enema), and approximately 24 hours after sensitization. The patients' pre-and-post operative liver function tests will be measured. Adverse events will be reported by direct questioning of all patients with regards to photosensitivity and gastrointestinal symptoms (nausea, vomiting), and by measuring blood pressure and heart rate. Our objectives and endpoints are: 1) to determine if fluorescence with photodynamic diagnostics is selective for colorectal cancer, 2) to determine if photodynamic diagnostics has the potential to improve the detection of malignant cell after neoadjuvant chemotherapy and radiation, and 3) to determine if photodynamic diagnostics can provide an accurate depiction of the extent of disease burden not visible with normal white light sigmoidoscopy to the naked human eye.

Study Overview

• Status: Withdrawn
• Conditions: Colorectal Cancer; Photodynamic Diagnosis
• Intervention / Treatment: Drug: Cysview

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients older than 18 years of age with diagnosed colorectal cancer.
• Colorectal cancer patients treated with Chemotherapy and external beam radiation therapy

Exclusion Criteria:

• 1) Liver cirrhosis
• 2) Acute or chronic hepatitis
• 3) Elevated liver function tests of unknown etiology with elevation of transaminases of more than 3 times normal levels
• 4) Known porphyria
• 5) Pregnancy
• 6) Expected lack of compliance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Blue Light Cystoscopy with Cysview®; The enema will be administered to participant. Fluorescence sigmoidoscopy will be performed with white light then blue excitation light after retention of the enema for 60 minutes, followed by a rest time of up to 30 minutes before rectoscopy. Post-operative surgical specimens will be collected for further fluorescence microscopy studies and pathological correlation of fluoresce with malignant pathology/histology as the gold standard.

Drug: Cysview; 250 mL enema containing 1.6 mmol of hexaminolevulinate; Other Names: hexaminolevulinate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fluorescence with photodynamic diagnostics (PDD) in colorectal cancer	To observe red fluorescence wirh PDD when lesions are illuminate with blue fluorescence during fluorescence sigmoidoscopy.	9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detect malignant lesions	Using the images of fluorescence sigmoidoscopy, detect malignant lesions after neoadjuvant chemotherapy and radiation.	9 months

Other Outcome Measures

Outcome Measure	Time Frame
Accurate depiction of the extent of disease burden by correlating pre-and post surgical results after neoadjuvant chemotherapy and radiation.	9 months

Collaborators and Investigators

• Sponsor: Dr. Te Vuong
• Collaborators: KARL STORZ Endoscopy-America, Inc.

Publications and helpful links

General Publications

• Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015 Mar;65(2):87-108. doi: 10.3322/caac.21262. Epub 2015 Feb 4.
• Endlicher E, Gelbmann CM, Knuchel R, Furst A, Szeimies RM, Golder SK, Scholmerich J, Lottner C, Messmann H. Hexaminolevulinate-induced fluorescence endoscopy in patients with rectal adenoma and cancer: a pilot study. Gastrointest Endosc. 2004 Sep;60(3):449-54. doi: 10.1016/s0016-5107(04)01723-7.
• Mayinger B, Neumann F, Kastner C, Degitz K, Hahn EG, Schwab D. Early detection of premalignant conditions in the colon by fluorescence endoscopy using local sensitization with hexaminolevulinate. Endoscopy. 2008 Feb;40(2):106-9. doi: 10.1055/s-2007-967019. Epub 2008 Jan 16.
• Mayinger B, Neumann F, Kastner C, Haider T, Schwab D. Hexaminolevulinate-induced fluorescence colonoscopy versus white light endoscopy for diagnosis of neoplastic lesions in the colon. Endoscopy. 2010 Jan;42(1):28-33. doi: 10.1055/s-0029-1243804. Epub 2010 Jan 11.
• Pietzak EJ. The Impact of Blue Light Cystoscopy on the Diagnosis and Treatment of Bladder Cancer. Curr Urol Rep. 2017 May;18(5):39. doi: 10.1007/s11934-017-0685-8.

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2018
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): April 1, 2019

Study Registration Dates

• First Submitted: August 30, 2017
• First Submitted That Met QC Criteria: September 1, 2017
• First Posted (Actual): September 5, 2017

Study Record Updates

• Last Update Posted (Actual): September 18, 2019
• Last Update Submitted That Met QC Criteria: September 17, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: PDD; Fluorescence Sigmoidoscopy; Photodynamic Diagnosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 17-140

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No