Early Feasibility Study of Endoscopic Optical Coherence Tomography for Screening and Diagnosis of Colorectal Precancerous and Malignant Polyps
Phase: NA
Conditions: Colon Cancer, Rectal Cancer, Cancer of the Rectum, Cancer of the Colon, Precancerous Polyp, Malignant Polyp
Sponsor: Washington University School of Medicine

Protocol Title: 
Early feasibility study of endoscopic optical coherence tomography for 
screening and diagnosis of colorectal precancerous and malignant polyps 
 
NCT#: 
NCT05179837 
 
Version: 
05/31/2023 

Version 05/31/2023 
 
page 1 of 27 
 
 
Early feasibility study of endoscopic optical coherence tomography for screening and 
diagnosis of colorectal precancerous and malignant polyps 
 
Washington University School of Medicine 
Division of Gastroenterology 
660 South Euclid Avenue, Campus Box 8124 
St. Louis, MO  63110 
 
Protocol #: 202103151 
Version Date: 31 May 2023 
 
 
Principal Investigator: 
Vladimir Kushnir, M.D. 
Phone: (314) 362-3685 
E-mail: vkushnir@wustl.edu  
 
Sub-Investigators 
 
 
 
Modality 
Quing Zhu, Ph.D. 
 
 
 
Biomedical Engineering  
Vladimir Lamm, M.D. 
 
 
Gastroenterology 
Esther Lu (Jingxia Liu), M.S, Ph.D.  
Biostatistics  
 
Study Device: 
 
Optical coherence tomography (OCT) probe 
NCT#: 
Pending 
Funded by: 
Departmental funds 
 
 
 
 
CONFIDENTIAL 
The information contained in this document is regarded as confidential and, except to the extent necessary to 
obtain informed consent, may not be disclosed to another party unless law or regulations require such 
disclosure.  Persons to whom the information is disclosed must be informed that the information is 
confidential and may not be further disclosed by them 
 
 
 

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STATEMENT OF COMPLIANCE 
The trial will be carried out in accordance with International Conference on Harmonisation Good 
Clinical Practice (ICH GCP) and the following:  
 
• United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 
CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812)  
 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the Institutional Review Board (IRB) for review and approval.  Approval of both 
the protocol and the consent form must be obtained before any participant is enrolled.  Any 
amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study.  In addition, all changes to the consent form will be IRB-approved; a 
determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form. 
 
 
 
 
 
 
 
 

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Table of Contents 
 
PROTOCOL SUMMARY .............................................................................................................. 4 
1.0 
INTRODUCTION .............................................................................................................. 6 
1.1 
Study Rationale ............................................................................................................... 6 
1.2 
Background ..................................................................................................................... 6 
1.3 
Study Design ................................................................................................................... 8 
1.4 
Risk/Benefit Assessment ................................................................................................ 8 
2.0 
OBJECTIVES AND ENDPOINTS .................................................................................. 10 
3.0 
STUDY POPULATION ................................................................................................... 10 
3.1 
Inclusion Criteria .......................................................................................................... 10 
3.2 
Exclusion Criteria ......................................................................................................... 10 
3.3 
Inclusion of Women and Minorities ............................................................................. 10 
4.0 
REGISTRATION PROCEDURES .................................................................................. 10 
4.1 
Confirmation of Patient Eligibility ............................................................................... 11 
4.2 
Patient Registration in the Siteman Cancer Center OnCore Database ......................... 11 
4.3 
Assignment of UPN ...................................................................................................... 11 
4.4 
Screen Failures .............................................................................................................. 11 
5.0 
STUDY PROCEDURES .................................................................................................. 11 
5.1 
Recruitment ................................................................................................................... 11 
5.2 
Study Procedures .......................................................................................................... 12 
5.3 
Definitions of Evaluability ............................................................................................ 13 
6.0 
REGULATORY AND REPORTING REQUIREMENTS .............................................. 13 
6.1 
WU PI Reporting Requirements ................................................................................... 13 
6.2 
Exceptions to Expedited Reporting .............................................................................. 14 
7.0 
DATA SUBMISSION SCHEDULE ................................................................................ 14 
7.1 
Adverse Event Collection in the Case Report Forms ................................................... 14 
8.0 
SCHEDULE OF ACTIVITIES......................................................................................... 15 
9.0 
DATA AND SAFETY MONITORING ........................................................................... 15 
10.0 
STATISTICAL CONSIDERATIONS.............................................................................. 16 
10.1 
Study Design ................................................................................................................. 16 
10.2 
Endpoints ...................................................................................................................... 16 
10.3 
Sample Size Calculation ............................................................................................... 16 
10.4 
Accrual .......................................................................................................................... 17 
10.5 
Statistical Analyses ....................................................................................................... 17 
10.6 
Early Stopping Rules .................................................................................................... 17 
11.0 
REFERENCES ................................................................................................................. 19 
12.0 
FIGURES .......................................................................................................................... 21 
APPENDIX A: Definitions for Adverse Event Reporting ........................................................... 24 
APPENDIX B: Reporting Timelines ............................................................................................ 26 
 
 

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PROTOCOL SUMMARY 
 
Title: 
Early feasibility study of endoscopic optical coherence tomography 
for screening and diagnosis of colorectal precancerous and malignant 
polyps.  
Study Description: 
Colorectal cancer arises from the mucosal layer of the colon.  Current 
screening is performed by flexible endoscopy, which involves visual 
inspection of the mucosal lining of the colon and rectum with an 
optical camera mounted on the endoscope, with abnormal areas 
being biopsied.  This method is somewhat limited in that there are 
no readily available surface pattern or morphological classification 
systems with adequate sensitivity or specificity to evaluate extent of 
submucosal invasion (deep, superficial, or none). Optical coherence 
tomography (OCT) using pattern recognition is a high-resolution 
imaging modality.  There is currently an unmet need to predict depth 
of invasion for colonic tumors to decide on applicability of 
endoscopic (endoscopic submucosal dissection or endoscopic 
mucosal resection) vs. surgical therapy.  Our hypothesis is that OCT 
will have a higher diagnostic accuracy for determining depth of 
submucosal invasion compared to existing modalities.  We will first 
aim to assess the procedural feasibility and safety of using an OCT 
probe during routine colonoscopy with an early feasibility study. 
This study will identify appropriate modifications to the device and 
help with development of subsequent clinical study protocols.  The 
eventual goal is to assess the diagnostic accuracy of OCT imaging 
for predicting depth of invasion of colonic tumors. 
Objectives: 
Primary Objective:  
To demonstrate the procedural feasibility of OCT during routine 
colonoscopy.   
 
Secondary Objective:  
• To describe the safety of the OCT probe during routine 
colonoscopy. 
• To evaluate the quality of OCT images using a machine 
learning algorithm. 
• To explore the diagnosis agreement between OCT imaging 
and pathology when a lesion is biopsied.   
Endpoints: 
Primary Endpoint:  
Whether a lesion can be adequately evaluated with OCT within 5 
minutes during a standard of care colonoscopy.      
 
Secondary Endpoints:  
• Adverse events related to OCT imaging during routine 
colonoscopy.  
• Whether OCT image is successfully captured using machine 
learning algorithm.  

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• Weighted kappa 
Study Population: 
Fifty-four adults undergoing standard of care colonoscopy for the 
evaluation of colonic polyps will be enrolled in this study. 
Phase: 
N/A 
Description of Sites / 
Facilities Enrolling: 
This study will enroll patients at Washington University School of 
Medicine. 
Description 
of 
Study 
Intervention: 
The OCT probe (Section 12, Figure 1) is attached to an 
approximately 3-meter wire that is attached to the OCT fiber probe 
system setup. This setup consists of a power supply unit, and a 
control platform that controls fiber probe rotation and retraction.  The 
OCT probe will be advanced through the colonoscope instrument 
channel (Section 12, Figure 2).  
Study Duration: 
12 months (enrollment) + 1 day (participation) + 2 days (follow-up) 
+ 6 months (analysis) 
Participant Duration: 
3 days 
 
 
 
 
 
 
 
 
 
 
 
 

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1.0 
INTRODUCTION 
 
1.1 
Study Rationale 
 
Endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) are 
used to treat superficial colorectal neoplasms but are contraindicated by deeply invasive 
colorectal cancer. Estimating depth of invasion is crucial to guiding treatment strategies. 
Current methods for estimating this depth are not readily available, expensive, or lack 
accuracy. There have been no in vivo studies using optical coherence tomography to 
differentiate between different types of polyps.  We would like to determine the procedural 
feasibility and safety of using an optical coherence tomography (OCT) probe for evaluation 
of colonic polyps during routine colonoscopy.  
 
If this feasibility study is successful we will then plan a study of patients with large complex 
polyps referred for EMR or ESD to Washington University, where we would evaluate the 
accuracy of the OCT probe for determining depth of submucosal invasion. 
 
1.2 
Background 
 
1.2.1 Colonoscopy Polyp Detection Rate and Adenoma Detection Rate  
 
Guidelines support performance targets for adenoma detection rate of 25% for a 
mixed gender population (20% in women and 30% in men). Polyp detection rate 
(PDR) and adenoma detection rate (ADR) increase with age, with one study 
showing a  PDR/ADR ratio of 16.9%/6.3% for patients in their 20s, 33%/14.0% for 
patients in their 30s, 43.5%/28.7% for patients in their 40s, 54.3%/38.4% for 
patients in their 50s, 61.2%/46.2% for patients in their 60s, 68.7%/55.8% for 
patients in their 70s, and 65.9%/56.1% for patients in their 80s (P < 0.001) [1]. 
Polyp detection rate is relevant for patient selection. Because we want to maximize 
the chance that a patient will have a polyp (hyperplastic, adenoma, etc.) that OCT 
can image, inclusion criteria will include age 40 years or older.    
 
1.2.2 Diagnostic Accuracy of Depth of Invasion  
 
Being able to differentiate between deep (> 1mm) and superficial (<1 mm) 
submucosal is a crucial branch point in clinical decision making. Deep submucosal 
invasion carries an 8-23% risk of lymph node metastasis. These lesions should be 
referred to surgery. On the other hand, if a lesion has superficial submucosal 
invasion and the endoscopist completes "en bloc" resection with EMR or ESD, then 
this is considered curative. While NICE 3 classification (Section 12, Figure 3) has 
up to a 94% accuracy for lesions with deep submucosal invasion, there are no 
readily available surface pattern or morphological classification systems with 
adequate sensitivity or specificity for superficial submucosal invasion [2]. 
Increasing diagnostic accuracy for lesions with superficial submucosal invasion 
would aid in the decision-making process of whether or not to refer a patient with 
a suspicious polyp to colorectal surgery or for endoscopic therapy. 

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Current options for estimation of invasion depth include gross features on 
endoscopy, narrow band imaging, magnifying chromoendoscopy, endoscopic 
ultrasonography, endocytoscopy, and confocal laser endomicroscopy. The only 
modality in widespread use is narrow band imaging, which does not require the use 
of magnification or dye spray. 
 
Narrow band imaging using the NICE classification is limited in identifying 
superficial submucosal invasion. JNET (Section 12, Figure 4) was formed to help 
better differentiate between low grade intramucosal neoplasia and superficial 
submucosal invasion. This classification has an accuracy of <80% for lesions with 
superficial submucosal invasion and requires magnifying chromoendoscopy, which 
is not readily available [3]. Endoscopic ultrasonography is comparable to 
magnifying chromoendoscopy with neither modality having sufficient diagnostic 
accuracy for depth of invasion [4]. 
 
1.2.3 Optical Coherence Tomography (OCT) 
 
In prior work, several research groups have demonstrated promising results that 
suggest OCT, an established high resolution imaging modality [5,6,7], may address 
the shortcomings of traditional camera endoscopy in the upper gastrointestinal tract 
[8,9,10] or large intestine [11,12,13]. OCT has been shown to accurately 
differentiate abnormal from normal tissue in multiple organs as an “optical biopsy” 
tool [14,15,16] in both murine and human colorectal models [17,18,19,20]. 
However, clinical application of the technology is complicated by the large volume 
of data generated and the subtle qualitative differences between normal and 
abnormal tissue. 
 
 
The success of convolutional neural networks (CNN) in computer vision tasks has 
popularized deep learning for CAD imaging [21,22,23]. CNNs have successfully 
been applied to OCT images for ophthalmological, esophageal, and cardiac 
diseases [24,25,26]. Moreover, CNN has also been applied to colon cancer 
diagnostics in an image classification [27,28,29]. 
 
The Zhu lab reported the use of pattern-recognition OCT(PR-OCT) in 
differentiating normal from neoplastic colorectal tissue (Section 12, Figure 5). 
Using RetinaNet, a novel neural network architecture for pattern recognition tasks, 
a dentate structural pattern was used as a structural marker of normal specimens 
and in PR-OCT prediction. This method leverages the recent advancement in object 
detection, which localizes and classifies the diagnostic features at real-time, and 
achieves an accurate classification result. This initial study demonstrated the 
feasibility of using PR-OCT as an "optical biopsy" tool to assist physicians in real-
time for mucosal neoplasms screening [30]. 
 
The current OCT system developed by Zhu et al has so far been tested on a limited 
number of specimens in an ex-vivo study using specimens collected after surgical 

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resection (16 normal, 2 adenomatous polyps, 4 treated areas (2 complete 
responders, 2 non-responders). Using OCT and training this input with deep 
learning, the Zhu lab achieved a sensitivity and specificity of 100% and 99.7%, 
respectively for normal vs cancerous tissue in an ex-vivo model. 
 
Currently, there are limited studies that focus on determining sensitivity and 
specificity of OCT for evaluation of different types of polyps. Further, there are no 
studies using this technology in real time for colorectal cancer screening. 
 
1.3 
Study Design 
 
1.3.1 Overall Design 
 
This is a one-arm non-blinded study to investigate the feasibility of an OCT probe 
for the patients undergoing routine screening or surveillance colonoscopy. Time 
added to length of overall procedure will serve as a surrogate endpoint towards 
evaluating ease of procedure for the endoscopist and endoscopy staff. We expect to 
find polyps in the enrolled patients. One polyp per patient will be imaged. A 
population of patients undergoing routine colonoscopy on the 8th floor of Center 
for Advanced Medicine will be targeted. The duration of each patient’s 
participation will last from the time of screening to 48 hours after the colonoscopy 
to evaluate for adverse events.  
 
Patients will be screened for the study prior to undergoing routine colonoscopy. 
The OCT probe system setup will be placed in a pre-determined room in the GI 
endoscopy suite on 8th floor of Center for Advanced Medicine. Once a polyp is 
found (hyperplastic, adenoma, or malignant appearing), the OCT probe will be 
advanced through the channel of the colonoscope. Image capture is expected to take 
around 3 minutes. We will have a goal of imaging one polyp per patient. If no 
polyps are found then the OCT probe will be used to image an area of normal 
colonic mucosa.   
 
1.3.2 Scientific Rationale for Study Design 
 
Our goal is to assess feasibility of using OCT probe during routine colonoscopy. 
Therefore, we are going to screen patients 40 years of age or older for inclusion in 
this study because these patients have a higher chance of having polyps that can be 
imaged. Because we are assessing the feasibility of a new device, there will be no 
blinding or randomization. The secondary objective of correlating OCT images 
with pathology is exploratory in nature.   
 
1.4 
Risk/Benefit Assessment 
 
1.4.1 Known Potential Risks 
 
Known potential risks include added procedure sedation time as a result of OCT 

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imaging. We expect each polyp to be imaged within the span of 3 minutes and do 
not expect adding more than 5 minutes to total procedure time. Risk of infection 
and bleeding is <1% in standard of care colonoscopy. We don’t expect the OCT 
probe to increase these risks. A table of common adverse events during a routine 
colonoscopy (with rates in percentages) is presented below.  Adverse event rates in 
this study will be compared to the historic AE rates from this table. 
 
Adverse Events 30 days After Outpatient Screening or Follow-Up Colonoscopy 
[31] 
 
 
Screening  
Surveillance  
No 
Polypectomy  
Polypectomy 
Death  
0.03% 
0.06% 
0.02% 
0.05% 
Perforation 
0.04% 
0.12% 
0.03% 
0.07% 
Hemorrhage 
0.27% 
0.38% 
0.08% 
0.50% 
Diverticulitis 
0.18% 
0.22% 
0.18% 
0.20% 
Abdominal pain 2.64% 
2.21% 
2.62% 
2.56% 
Any serious 
adverse event* 
0.47% 
0.68% 
0.27% 
0.74% 
Hospitalizations 1.11% 
1.61% 
0.94% 
1.43% 
Emergency 
Department or 
Urgent Care 
Visit 
2.26% 
3.01% 
2.23% 
2.47% 
 
*Serious adverse events include perforation, hemorrhage, or diverticulitis.  
 
1.4.2 Known Potential Benefits 
 
There is no direct benefit to the patient. We hope that this feasibility study will 
answer the question of whether or not this OCT probe is feasible in routine 
colonoscopy. This may lead to another study of assessing the diagnostic accuracy 
of the OCT probe.  
 
1.4.3 Assessment of Potential Risks and Benefits 
 
OCT is an older technology used by many research groups and commercially in eye 
clinics. The probe is made by Dr. Zhu’s lab. We anticipate that the potential benefits 
outweigh the minimal risks.  
 
 

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2.0 
OBJECTIVES AND ENDPOINTS 
 
Objectives 
Endpoints 
Primary 
To demonstrate the procedural feasibility of 
OCT during routine colonoscopy  
Whether a lesion can be adequately evaluated 
with OCT within 5 minutes during a standard of 
care colonoscopy.      
 
Secondary 
To describe safety of OCT probe during 
routine colonoscopy 
Adverse events related to OCT imaging during 
routine colonoscopy 
To evaluate the quality of OCT images using 
a machine learning algorithm.  
Whether OCT image is successfully captured 
using machine learning algorithm 
To explore the diagnosis agreement between 
OCT imaging and pathology when a lesion is 
biopsied. 
Weighted kappa 
  
 
3.0 
STUDY POPULATION 
 
3.1 
Inclusion Criteria 
 
1. Undergoing standard of care colonoscopy for the evaluation of colonic polyps. 
 
2. At least 40 years of age. 
 
3. Ability to understand and willingness to sign an IRB approved written informed 
consent document (or that of legally authorized representative, if applicable). 
 
3.2 
Exclusion Criteria 
 
1. Pregnant and/or breastfeeding. 
 
2. Unable to tolerate sedation. 
 
3.3 
Inclusion of Women and Minorities 
 
Both men and women and members of all races and ethnic groups are eligible for this trial. 
 
 
4.0 
REGISTRATION PROCEDURES 
 
Patients must not start any protocol intervention prior to registration through the Siteman 
Cancer Center. 
 
The following steps must be taken before registering patients to this study: 

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1. Confirmation of patient eligibility 
2. Registration of patient in the Siteman Cancer Center database 
3. Assignment of unique patient number (UPN) 
 
4.1 
Confirmation of Patient Eligibility 
 
Confirm patient eligibility by collecting the information listed below: 
 
1. the registering MD’s name 
2. Patient’s race, sex, and DOB 
3. Three letters (or two letters and a dash) for the patient’s initials 
4. Copy of signed consent form 
5. Completed eligibility checklist, signed and dated by a member of the study team 
6. Copy of appropriate source documentation confirming patient eligibility 
 
4.2 
Patient Registration in the Siteman Cancer Center OnCore Database 
 
All patients must be registered through the Siteman Cancer Center OnCore database. 
 
4.3 
Assignment of UPN 
 
Each patient will be identified with a unique patient number (UPN) for this study.  All data 
will be recorded with this identification number on the appropriate CRFs. 
 
4.4 
Screen Failures 
 
Screen failures are defined as participants who consent to participate in the clinical trial 
but are not subsequently entered in the study.  A minimal set of screen failure information 
is required to ensure transparent reporting of screen failure participants, to meet the 
Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities.  Minimal information includes demography, 
screen failure details, eligibility criteria, and any serious adverse event (if applicable).   
 
 
5.0 
STUDY PROCEDURES 
 
5.1 
Recruitment 
 
Adult patients scheduled to undergo a routine colonoscopy for screening or surveillance of 
colon polyps, evaluation of GI bleeding, post-colon cancer resection surveillance, or 
reassessment of prior colon polyp will be screened for the study. Patients will be identified 
as candidates for the study from the BJH Surgery schedule the day before they come in. 
One of the investigators or a research assistant will discuss the study with potential 
participants in the pre-endoscopy area.  Those subjects who qualify for the study based on 
eligibility criteria will be invited to participate.  The consent process will take place in the 

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pre-endoscopy area. Those patients who wish to participate will sign the informed consent 
document and proceed to colonoscopy. 
 
5.2 
Study Procedures 
 
After consent, the endoscopist will perform a standard of care colonoscopy. We will enroll 
54 participants in the study and expect approximately 40 of these participants to have 
polyps. If a polyp is found, then OCT will be used to image that polyp. Patients with polyps, 
regardless of number found, will have either one tubular adenoma (NICE type 2) imaged 
OR one hyperplastic polyp (NICE type 1) imaged. These polyps can be distinguished 
endoscopically using the NICE classification (see Section 12, Figure 1). If no polyps are 
found, then one area of normal mucosa will be imaged. We will have a goal of imaging an 
equal number of tubular adenomas and hyperplastic polyps. We will have a running log of 
the number of imaged tubular adenomas and hyperplastic polyps imaged to ensure that 
equal amounts of each type are imaged. If on the rare chance a malignant appearing colonic 
tumor (NICE type 3) is found, this and no other polyps will be imaged with OCT.  
 
Duration of using OCT probe as well as duration of the colonoscopy will be kept by 
endoscopy staff with a stopwatch. Initiation of colonoscopy will be time 00:00.  There will 
then be time marks for initiation of OCT imaging, end of OCT imaging, and end of 
colonoscopy.  In this way, the exact duration of OCT and the full duration of colonoscopy 
with OCT will be captured. 
 
Duration of OCT imaging will be from the time of guiding the OCT probe through the 
colonoscope to imaging, and withdrawal of OCT probe. The maximum time allotted to 
obtain OCT imaging will be 10 minutes.  Any OCT imaging that reaches the 10-minute 
mark will be stopped so that routine colonoscopy can resume.  A log of total procedure 
duration is kept for every standard of care colonoscopy.  
 
When a polyp or area of normal mucosa to be examined with OCT is identified, the location 
of the area imaged will be documented (sigmoid, descending colon, transverse colon, 
ascending colon, cecum, etc.) by a registered nurse.  The OCT catheter probe will be guided 
through the instrument channel of the colonoscope with the colonoscope still in the patient. 
This will take under approximately 5 seconds. The OCT probe will then be moved to make 
contact with the mucosa.  The probe will then take several hundred high-resolution images 
of the lesion, with an expected duration of 2-3 minutes.  During this time, the endoscopist 
will maintain view of the lumen and/or polyp. After completion of OCT imaging, the OCT 
probe will be removed, which will take approximately under 5 seconds.  Colonoscopy will 
then resume to complete a full routine examination.  
 
All procedures will be performed by a gastroenterologist experienced in advanced imaging 
techniques or by a fellow under direct supervision.  
 
There will be a toxicity assessment at baseline and at the observation period after 
colonoscopy.  Patients will also be contacted by phone approximately 48 hours after 
colonoscopy to collect information on any AEs experienced. 

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The standard of care pathology report for any area biopsied will be accessed from the 
medical record when available in order to compare the pathological findings with the 
diagnosis determined by OCT imaging. 
 
5.3 
Definitions of Evaluability 
 
A patient must have had at least one colonic polyp or area of normal mucosa selected for 
OCT imaging in order to be evaluable for the feasibility endpoint.  Any patient who does 
not have any area of mucosa imaged by OCT (either due to poor bowel prep, anesthesia 
complications, etc.), will be considered inevaluable for the feasibility endpoint and will be 
replaced. 
 
All patients who undergo colonoscopy using the OCT probe are evaluable for toxicity and 
evaluation of imaging quality.  Patients are evaluated for AEs from time of colonoscopy 
until 48 hours after colonoscopy. 
 
 
6.0 
REGULATORY AND REPORTING REQUIREMENTS 
 
The entities providing oversight of safety and compliance with the protocol require reporting as 
outlined below.  Please refer to Appendix A for definitions and Appendix B for a grid of reporting 
timelines. 
 
Adverse events will be tracked from time of colonoscopy through 48 hours after end of 
colonoscopy.  All adverse events must be recorded on the toxicity tracking case report form (CRF) 
with the exception of: 
• Baseline adverse events, which shall be recorded on the medical history CRF 
 
Refer to the data submission schedule in Section 7 for instructions on the collection of AEs in the 
EDC. 
 
Reporting requirements for Washington University study team may be found in Section 6.1. 
 
6.1 
WU PI Reporting Requirements 
 
6.1.1 Reporting to the Human Research Protection Office (HRPO) at 
Washington University 
 
Reporting will be conducted in accordance with Washington University IRB 
Policies. 
 
Pre-approval of all protocol exceptions must be obtained prior to implementing the 
change. 
 

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6.1.2 Reporting to the Quality Assurance and Safety Monitoring 
Committee (QASMC) at Washington University 
 
The PI (or designee) is required to notify the QASMC of any unanticipated 
problems involving risks to participants or others occurring at WU or any BJH or 
SLCH institution that has been reported to and acknowledged by HRPO.  
(Unanticipated problems reported to HRPO and withdrawn during the review 
process need not be reported to QASMC.) 
 
QASMC must be notified within 10 days of receipt of IRB acknowledgment via 
email to qasmc@wustl.edu.  Submission to QASMC must include the myIRB form 
and any supporting documentation sent with the form. 
 
6.2 
Exceptions to Expedited Reporting 
 
Events that do not require expedited reporting as described in Section 6.1 include: 
• planned hospitalizations 
• hospitalizations < 24 hours 
• respite care 
• events related to disease progression 
 
Events that do not require expedited reporting must still be captured in the EDC. 
 
 
7.0 
DATA SUBMISSION SCHEDULE 
 
Case report forms with appropriate source documentation will be completed according to the 
schedule listed in this section. 
 
Case Report Form 
Submission Schedule 
Original Consent Form 
Prior to registration 
On-Study Form 
Medical History Form 
Prior to colonoscopy 
Colonoscopy Procedure Form 
OCT Data Form 
Following colonoscopy 
Toxicity Form 
Baseline 
Post-colonoscopy observation period 
48 hours following colonoscopy 
 
7.1 
Adverse Event Collection in the Case Report Forms 
 
All adverse events that occur beginning with colonoscopy (minus exceptions defined in 
Section 6.0) must be captured in the Toxicity Form.  Baseline AEs should be captured on 
the Medical History Form. 
 
 

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8.0 
SCHEDULE OF ACTIVITIES 
 
 
Screening 
Colonoscopy 
48 hours after 
colonoscopy 
Informed consent 
X 
 
 
Pregnancy test1 
 
X 
 
Colonoscopy 
 
X 
 
AE monitoring 
 
X 
X 
1. Women of childbearing potential only 
 
 
9.0 
DATA AND SAFETY MONITORING 
 
In compliance with the Washington University Institutional Data and Safety Monitoring Plan, the 
Principal Investigator will provide a Data and Safety Monitoring (DSM) report to the Washington 
University Quality Assurance and Safety Monitoring Committee (QASMC) semi-annually 
beginning six months after accrual has opened (if at least one patient has been enrolled) or one 
year after accrual has opened (if no patients have been enrolled at the six-month mark). 
 
The Principal Investigator will review all patient data at least every six months, and provide a 
semi-annual report to the QASMC. This report will include: 
• HRPO protocol number, protocol title, Principal Investigator name, data coordinator 
name, regulatory coordinator name, and statistician 
• Date of initial HRPO approval, date of most recent consent HRPO approval/revision, 
date of HRPO expiration, date of most recent QA audit, study status, and phase of study 
• History of study including summary of substantive amendments; summary of accrual 
suspensions including start/stop dates and reason; and summary of protocol exceptions, 
error, or breach of confidentiality including start/stop dates and reason 
• Study-wide target accrual and study-wide actual accrual 
• Protocol activation date 
• Average rate of accrual observed in year 1, year 2, and subsequent years 
• Expected accrual end date 
• Objectives of protocol with supporting data and list the number of participants who 
have met each objective 
• Early stopping rules with supporting data and list the number of participants who have 
met the early stopping rules 
• Summary of toxicities 
• Abstract submissions/publications 
• Summary of any recent literature that may affect the safety or ethics of the study  
 
The study principal investigator and Research Patient Coordinator will monitor for serious 
toxicities on an ongoing basis. Once the principal investigator or Research Patient Coordinator 
becomes aware of an adverse event, the AE will be reported to the HRPO and QASMC according 
to institutional guidelines. 
 
 

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10.0 
STATISTICAL CONSIDERATIONS 
 
10.1 
Study Design  
 
This is a one-arm non-blinded study to investigate the feasibility of an OCT probe for 
patients undergoing routine screening or surveillance colonoscopy. The primary objective 
is to demonstrate the procedural feasibility of OCT during routine colonoscopy. Secondary 
objectives aim to describe the safety of the OCT probe, evaluate the quality of OCT images 
using a machine learning algorithm, and explore the diagnosis agreement between OCT 
imaging and pathology when a lesion is biopsied. OCT imaging through a catheter directed 
probe during routine colonoscopy will be measured by the duration of the entire procedure 
as well as duration of the OCT procedure itself. 
 
10.2 
Endpoints 
 
Primary endpoint is whether a lesion can be adequately evaluated with OCT within 5 
minutes during a standard of care colonoscopy. If the proportion of the patients whose 
procedure length using an OCT probe during routine colonoscopy is within 5 minutes is 
greater than 75%, then the feasibility is defined in this study.  
 
Secondary endpoints include: 
• AEs related to OCT imaging during routine colonoscopy 
• Whether OCT image is successfully captured using machine learning algorithm, 
coded as “good” or “noisy”. The OCT imaging catheter will be calibrated before 
each patient study to ensure that the catheter system is working properly. In an in 
vivo study of the catheter, we expect some images will be distorted due to patient 
movement, sub-optimal contact with the mucosa, etc. The machine learning 
algorithm will judge image quality based on number of colonic crypts visualized 
(see Section 12, Figure 5). We hypothesize that the proportion of good OCT images 
is greater than 90%. 
• Weighted Kappa.  Clinical pathology is the gold standard for diagnosis.  Diagnosis 
from both OCT and clinical pathology will be assigned as normal mucosa, 
hyperplastic polyp, tubular adenoma, sessile serrated adenoma, or colorectal 
cancer.  Based on ex vivo data from Dr. Zhu’s lab, we hypothesize that there will 
be an over 80% agreement rate in this feasibility study.  
 
10.3 
Sample Size Calculation  
 
The sample size calculation is based on the primary endpoint of feasibility only. The 
primary hypothesis is that the proportion of the patients who have OCT imaging which 
adds 5 minutes or less to the duration of standard of care colonoscopy is greater than 75%. 
The null hypothesis for feasibility is 75% and the alternative hypothesis is 90%.  H0: 
p<75% Ha: p>75% (expect it to be 90% in clinical practice). A sample size of 54 patients 
achieves 80.1% power to detect a difference of 15% using a two-sided exact test at a 
significance level of 5% with the assumption that the proportion is 75%. 
 

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10.4 
Accrual  
 
We perform screening and surveillance colonoscopies in about 10-15 patients per day at 
Barnes Jewish Hospital with similar characteristics and estimate approximately 5-10 
patients/day may be eligible for and will participate in this trial. We anticipate enrolling 
our goal of 54 patients in about 3-4 weeks.   
 
10.5 
Statistical Analyses  
 
10.5.1 Patient Disposition  
 
The number of patients discontinued, the reasons for discontinuation, and the 
duration of OCT imaging administered will be summarized by patient and by 
reason for discontinuation.  
 
10.5.2 Protocol Deviations  
 
All significant deviations will be summarized by patient and by type of deviation.  
 
10.5.3 Demographics and Baseline Characteristics  
 
Subject demographic and clinical characteristics will be summarized to 
characterize the population. Descriptive summaries will include means, standard 
deviations, medians, ranges for continuous variables and frequency and percentage 
for categorical variables. They are presented by total and each arm, respectively.  
 
10.5.4 Endpoint Analysis  
 
Proportions of the patients whose procedure length using an OCT probe during 
routine colonoscopy is within 5 minutes and who have good OCT images, as judged 
by a machine learning algorithm, will be provided. Their associated 95% 
confidence intervals (CIs) will be calculated assuming a binomial distribution. The 
descriptive statistics will be presented including frequency, type, and severity of 
AEs related to OCT imaging during routine colonoscopy. Weighted kappa and 95% 
CI will be computed for the agreement between OCT imaging and pathology for 
all enrolled patients.  All analyses will be conducted using SAS (SAS Institute, 
Cary, NC) at the two-sided 5% significance level. 
 
10.6 
Early Stopping Rules 
 
Toxicity, defined as study-related grade 3-5 SAEs, will be reviewed on a continuous basis. 
Early stopping will be based on the toxicity rate (TR) using the repeated significance 
testing of Pocock boundary with 80% power and 0.05 overall Type I error. We assume that 
no more than 5% is acceptable and a maximum-tolerated TR is 30%. The study will be 
halted if a study-related grade 3-5 SAE occurs in the first 2 patients, or 2 of the first 8 
patients, or 3 of the first 15 patients, or 4 of the first 24 patients, or 5 of the first 34 patients, 

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or 6 of the first 45 patients. R function-toxbdry was used for calculations. 
 
 
 

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11.0 
REFERENCES 
 
1. Bae T, Ha Y, Kim C, et al. Distribution of the colonoscopic adenoma detection rate 
according to age: is recommending colonoscopy screening for koreans over the age of 50 
safe?. Ann Coloproctol. 2015;31(2):46-51. doi:10.3393/ac.2015.31.2.46 
2. Shaukat A, Kaltenbach T, Dominitz JA, et al. Endoscopic Recognition and Management 
Strategies for Malignant Colorectal Polyps: Recommendations of the US Multi-Society Task 
Force on Colorectal Cancer. Am J Gastroenterol 2020; 115:1751-1767. 
3. Sumimoto K, Tanaka S, Shigita K, et al. Diagnostic performance of Japan NBI Expert Team 
classification for differentiation among noninvasive, superficially invasive, and deeply 
invasive colorectal neoplasia. Gastrointest Endosc 2017; 86:700-709.  
4. Lee BI, Matsuda T. Estimation of Invasion Depth: The First Key to Successful Colorectal 
ESD. Clin Endosc 2019; 52: 100-106.  
5. Huang D, Swanson EA, Lin CP, et al. Optical coherence tomography. Science 1991; 254: 
1178–1181. 
6. Chen CL, Wang RK. Optical coherence tomography based angiography. Biomed opt express 
2017;8: 1056–1082. 
7. Pahlevaninezhad H, Khorasaninejad M, Huang YW, et al. Nano-optic endoscope for high-
resolution optical coherence tomography in vivo. Nat photonics 2018;12: 540. 
8. Gora MJ, Quénéhervé L, Carruth RW, et al. Tethered capsule endomicroscopy for 
microscopic imaging of the esophagus, stomach, and duodenum without sedation in humans 
(with video). Gastrointest endosc. 2018;88: 830–840. 
9. van der Sommen F, Curvers WL, Nagengast WB. Novel developments in endoscopic 
mucosal imaging. Gastroenterology 2018; 154:1876–1886. 
10. Ahsen OO, Lee HC, Liang K, et al. Ultrahigh-speed endoscopic optical coherence 
tomography and angiography enables delineation of lateral margins of endoscopic mucosal 
resection: a case report. Therap Adv Gastroenterol 2017: 10:931–936. 
11. Kirtane TS, Wagh MS. Endoscopic optical coherence tomography (OCT): advances in 
gastrointestinal imaging. Gastroenterol Res Pract 2014;2014: 376367.  
12. Gora MJ, Suter MJ, Tearney GJ, Li X. Endoscopic optical coherence tomography: 
technologies and clinical applications. Biomed Opt Express 2017; 8:2405–2444. 
13. Welge WA, Barton JK. In vivo endoscopic Doppler optical coherence tomography imaging 
of the colon. Lasers Surg Med 2017; 49:249–257. 
14. Panta P, Lu CW, Kumar P, et al. Optical Coherence Tomography: Emerging In Vivo Optical 
Biopsy Technique for Oral Cancers. In: Panta P. (eds) Oral Cancer Detection. Springer, 
Cham.  
15. Freund JE, Faber DJ, Bus MT, et al. Grading upper tract urothelial carcinoma with the 
attenuation coefficient of in-vivo optical coherence tomography. Lasers Surg Med 2019; doi: 
10.1002/lsm.23079. 
16. Hariri LP, Mino-Kenudson M, Lanuti M, et  a;. Diagnosing lung carcinomas with optical 
coherence tomography. Ann Am Thorac Soc 2015; 12:193–201. 
17. Zagaynova E, Gladkova N, Shakhova N, et al. Endoscopic OCT with forward-looking probe: 
clinical studies in urology and gastroenterology. J Biophotonics 2008; 1:114–128. 
18. Adler DC, Zhou C, Tsai TH, et al. Three-dimensional endomicroscopy of the human colon 
using optical coherence tomography. Opt Express 2009; 17:784–796. 

Version 05/31/2023 
 
page 20 of 27 
19. Li Y, Zhu Z, Chen JJ, et al. Multimodal endoscopy for colorectal cancer detection by optical 
coherence tomography and near-infrared fluorescence imaging. Biomed Opt Express. 2019; 
10:2419–2429. 
20. Mavadia-Shukla J, Fathi P, Liang W, et al. High-speed, ultrahigh-resolution distal scanning 
OCT endoscopy at 800 nm for in vivo imaging of colon tumorigenesis on murine models. 
Biomed Opt Express 2018; 9:3731–3739. 
21. Esteva A, Kuprel B, Novoa RA, et al. Dermatologist-level classification of skin cancer with 
deep neural networks. Nature 2017; 542:115. 
22. Lu Y, Yu Q, Gao Y, et al. Identification of metastatic lymph nodes in MR imaging with faster 
region-based convolutional neural networks. Cancer Res 2018; 78: 5135-5143. 
23. Litjens G, Kooi T, Bejnordi BE, et al. A survey on deep learning in medical image analysis. 
Med Imaage Anal 2017; 42:60–88. 
24. Lee CS, Baughman DM, Lee AY. Deep learning is effective for classifying normal versus 
age-related macular degeneration OCT images. Ophthalmol Retina 2017; 1:322–327. 
25. Kermany DS, Goldbaum M, Cai W, et al. Identifying medical diagnoses and treatable 
diseases by image-based deep learning. Cell 2018; 172:1122–1131. 
26. Abdolmanafi A, Duong L, Dahdah N, et al. Deep feature learning for automatic tissue 
classification of coronary artery using optical coherence tomography. Biomed Opt Express 
2017;8:1203–1220. 
27. Chen PJ, Lin MC, Lai MJ, et al. Accurate classification of diminutive colorectal polyps using 
computer-aided analysis. Gastroenterology 2018; 154:568– 575. 
28. Sirinukunwattana K, e Ahmed Raza S, Tsang YW, et al. Locality sensitive deep learning for 
detection and classification of nuclei in routine colon cancer histology images. IEEE Trans 
Med Imaging 2016; 35:1196– 1206. 
29. Urban G, Tripathi P, Alkayali T, et al. Deep learning localizes and identifies polyps in real 
time with 96% accuracy in screening colonoscopy. Gastroenterology 2018;155(4): 1069-
1078. 
30. Zeng Y, Xu S, Chapman WC Jr, et al. Real-time colorectal cancer diagnosis using PR-OCT 
with deep learning. Theranostics 2020;10:2587-2596.  
31. Rutter CM, Johnson E, Miglioretti DL, et al. Adverse events after screening and follow-up 
colonoscopy. Cancer causes control 2012;23:289-296.  
 
 
 
 
 
 
 
 

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12.0 
FIGURES  
 
 
 
Figure 1. The OCT fiber probe laser focusing structure is depicted in Fig. 2. It is composed of a 
lead-in single mode fiber (SMF), a no-core fiber (NCF) for laser expansion, and a segment of 
gradient index (GRIN) fiber for laser focusing. The diameter of the GRIN fiber can be changed to 
realize different resolutions and working distances. The working distance is defined as the distance 
between the laser focus and the GRIN fiber end-face. In our experiments, GRIN fiber with a 230 
um diameter is used to realize a resolution of around 25 um and a working distance of around 1.8 
mm in air. The lengths of the GRIN fiber and NCF are 1300 um and 400 um, respectively.  
 
 
 
 
Figure 2. Colonoscope instrument channel.  
 

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Figure 3. NICE classification.  
 
 
 
 
 
Figure 4. JNET classification.  
 

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Figure 5. OCT imaging of normal colon tissue and colon cancer on left, corresponding pathology 
on right. 
 

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APPENDIX A: Definitions for Adverse Event Reporting 
 
A. Adverse Events (AEs) 
 
As defined in 21 CFR 312.32: 
 
Definition: any untoward medical occurrence associated with the use of a drug in humans, 
whether or not considered drug-related. 
 
Grading: the descriptions and grading scales found in the revised NCI Common Terminology 
Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for all toxicity reporting.  A 
copy of the CTCAE version 5.0 can be downloaded from the CTEP website. 
 
Attribution (relatedness), Expectedness, and Seriousness: the definitions for the terms 
listed that should be used are those provided by the Department of Health and Human Services’ 
Office for Human Research Protections (OHRP).  A copy of this guidance can be found on 
OHRP’s website: 
http://www.hhs.gov/ohrp/policy/advevntguid.html 
 
B. Suspected Adverse Reaction (SAR) 
 
As defined in 21 CFR 312.32: 
 
Definition: any adverse event for which there is a reasonable possibility that the drug caused 
the adverse event.  “Reasonable possibility” means there is evidence to suggest a causal 
relationship between the drug and the adverse event.  “Suspected adverse reaction” implies a 
lesser degree of certainty about causality than adverse reaction, which means any adverse event 
caused by a drug. 
 
C. Life-Threatening Adverse Event / Life Threatening Suspected Adverse Reaction  
 
As defined in 21 CFR 312.32: 
 
Definition: any adverse drug event or suspected adverse reaction is considered “life-
threatening” if, in the view of the investigator, its occurrence places the patient at immediate 
risk of death. It does not include an adverse event or suspected adverse reaction that, had it 
occurred in a more severe form, might have caused death. 
 
D.  Serious Adverse Event (SAE) or Serious Suspected Adverse Reaction 
 
As defined in 21 CFR 312.32: 
 
Definition:  an adverse event or suspected adverse reaction is considered “serious” if, in the 
view of the investigator, it results in any of the following outcomes: 
o Death 
o A life-threatening adverse event 

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o Inpatient hospitalization or prolongation of existing hospitalization 
o A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
o A congenital anomaly/birth defect 
o Any other important medical event that does not fit the criteria above but, based upon 
appropriate medical judgment, may jeopardize the subject and may require medical or 
surgical intervention to prevent one of the outcomes listed above 
 
E. Protocol Exceptions 
 
Definition: A planned change in the conduct of the research for one participant. 
 
F. Deviation 
 
Definition: Any alteration or modification to the IRB-approved research without prospective 
IRB approval.  The term “research” encompasses all IRB-approved materials and documents 
including the detailed protocol, IRB application, consent form, recruitment materials, 
questionnaires/data collection forms, and any other information relating to the research study. 
 
A minor or administrative deviation is one that does not have the potential to negatively impact 
the rights, safety, or welfare of participants or others or the scientific validity of the study. 
 
A major deviation is one that does have the potential to negatively impact the rights, safety, or 
welfare of participants or others or the scientific validity of the study. 
 

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APPENDIX B: Reporting Timelines 
 
Expedited Reporting Timelines 
Event 
HRPO 
QASMC 
Unanticipated problem 
involving risk to 
participants or others 
Report within 10 working days.  If the event results 
in the death of a participant enrolled at 
WU/BJH/SLCH, report within 1 working day. 
Report via email after 
IRB acknowledgment 
Major deviation 
Report within 10 working days.  If the event results 
in the death of a participant enrolled at 
WU/BJH/SLCH, report within 1 working day. 
 
A series of minor 
deviations that are being 
reported as a continuing 
noncompliance 
Report within 10 working days.   
 
Protocol exception 
Approval must be obtained prior to implementing the 
change 
 
Complaints 
If the complaint reveals an unanticipated problem 
involving risks to participants or others OR 
noncompliance, report within 10 working days.  If 
the event results in the death of a participant enrolled 
at WU/BJH/SLCH, report within 1 working day.  
Otherwise, report at the time of continuing review. 
 
Breach of confidentiality Within 10 working days. 
 
Incarceration 
If withdrawing the participant poses a safety issue, 
report within 10 working days.   
 
If withdrawing the participant does not represent a 
safety issue and the patient will be withdrawn, report 
at continuing review. 
 
 
Routine Reporting Timelines 
Event 
HRPO 
QASMC 
Adverse event or SAE 
that does not require 
expedited reporting 
If they do not meet the definition of an 
unanticipated problem involving risks to 
participants or others, report summary 
information at the time of continuing review 
Adverse events will be 
reported in the toxicity 
table in the DSM report 
which is typically due 
every 6 months. 
Minor deviation 
Report summary information at the time of 
continuing review. 
 
Complaints 
If the complaint reveals an unanticipated problem 
involving risks to participants or others OR 
noncompliance, report within 10 working days.  If 
the event results in the death of a participant 
enrolled at WU/BJH/SLCH, report within 1 
working day.  Otherwise, report at the time of 
continuing review. 
 
Incarceration 
If withdrawing the participant poses a safety 
issue, report within 10 working days.   
 
 

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Routine Reporting Timelines 
Event 
HRPO 
QASMC 
If withdrawing the participant does not represent a 
safety issue and the patient will be withdrawn, 
report at continuing review.