Early Feasibility Study For Evaluation Of The TraceIT® Tissue Spacer For Creating Space Between The Duodenum And Pancreas In Patients With Localized Pancreatic Cancer Undergoing Radiation Therapy
Phase: NA
Conditions: Pancreatic Cancer
Sponsor: Boston Scientific Corporation

 
 
 
 
 
 
 
 
 
 
 
EARLY FEASIBILITY STUDY FOR EVALUATION OF THE TRACEIT® TISSUE SPACER 
FOR CREATING SPACE BETWEEN THE DUODENUM AND PANCREAS IN PATIENTS 
WITH LOCALIZED PANCREATIC CANCER UNDERGOING RADIATION THERAPY 
 
THE TIPS PILOT STUDY 
 
 
NCT03998566 
 
27MAR2019 

Augmenix Inc. 
 
CONFIDENTIAL 
 
 
 
 
 
EARLY FEASIBILITY STUDY FOR EVALUATION OF THE TRACEIT® TISSUE 
SPACER FOR CREATING SPACE BETWEEN THE DUODENUM AND PANCREAS IN 
PATIENTS WITH LOCALIZED PANCREATIC CANCER UNDERGOING RADIATION 
THERAPY 
 
THE TIPS PILOT STUDY 
 
 
 
Investigational Protocol 
AGX-17-001-US 
REV. C 
 
March 27, 2019 
Sponsor: 
Augmenix Inc. 
 
 
 
 
 
201 Burlington Road 
 
 
 
 
 
Bedford, MA 01730 USA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
This investigational plan contains confidential information for use by Investigators participating in the Augmenix, Inc. clinical 
evaluation of the TraceIT Tissue Spacer.  This document should be maintained in a secure location and should not be copied or made 
available for review by any unauthorized person or firm. 
 
 
TraceIT is a registered trademark of Augmenix, Inc.
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TraceIT Tissue Spacer (TIPS Pilot)  
 
 
 
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Protocol AGX-17-001-US 
Rev. C:  March 27, 2019  
TABLE OF CONTENTS 
 
1 
SUMMARY OF CHANGES ...................................................................................... 4 
2 
PROTOCOL SUMMARY ........................................................................................ 20 
3 
PRINCIPAL CONTACTS ........................................................................................ 27 
4 
INTRODUCTION .................................................................................................... 28 
4.1 
Report of Prior Investigations ........................................................................... 29 
4.1.1 Pre-Clinical and Clinical Investigations ....................................................... 29 
4.2 
Description of Investigational Device .............................................................. 30 
4.3 
Indication .......................................................................................................... 30 
5 
STUDY SCOPE AND DURATION ........................................................................ 31 
6 
PROTOCOL ............................................................................................................. 31 
6.1 
Study Objectives ............................................................................................... 31 
6.1.1 Safety Endpoints ........................................................................................... 32 
6.1.2 Effectiveness Endpoints ................................................................................ 32 
6.1.3 Additional Data Collection ........................................................................... 32 
6.2 
Selection and Training of Investigators ............................................................ 32 
6.3 
Subject Selection ............................................................................................... 32 
6.3.1 Inclusion Criteria .......................................................................................... 32 
6.3.2 Exclusion Criteria ......................................................................................... 33 
6.4 
Study Procedures and Data Collection ............................................................. 35 
6.4.1 Study Schematics .......................................................................................... 35 
6.4.2 Subject Enrollment........................................................................................ 38 
6.4.3 Informed Consent.......................................................................................... 38 
6.4.4 Screening/Baseline Assessments (within 45 days prior to planned TraceIT 
hydrogel injection) .................................................................................................... 38 
6.4.5 Fiducial Placement and TraceIT Tissue Spacer Injection ............................. 39 
6.4.6 RT Planning and Radiation Treatment ......................................................... 40 
6.4.7 Follow-up for Non-Injection Subjects .......................................................... 41 
6.4.8 Post-injection RT Planning (less than 28 days following Index Procedure) 41 
6.4.9 RT Initiation .................................................................................................. 42 
6.4.10 
Final RT Fraction ...................................................................................... 42 
6.4.11 
Week 2-6 Following Completion of RT (Restaging & Evaluation for 
Potential Resection) .................................................................................................. 42 
6.4.12 
Resected Subjects (at time of resection) ................................................... 42 
6.4.13 
Resected Subjects (Histopathology record) .............................................. 43 
6.4.14 
Additional Follow-up at Month 3 (± 14 days) and Month 6 (± 14 days) 
Post-Index Procedure ................................................................................................ 43 
6.4.15 
Long Term Follow-Up (Month 12 ± 28 days and Month 18 ± 28 days) .. 43 
6.5 
Subject Withdrawal ........................................................................................... 44 
7 
STATISTICAL ANALYSIS .................................................................................... 44 
7.1 
Sample Size Determination ............................................................................... 44 
7.2 
General .............................................................................................................. 44 
7.3 
Analysis Populations ......................................................................................... 45 
7.3.1 Intent-to-Treat Population (ITT) ................................................................... 45 
7.3.2 Modified Intent-to-Treat Population (MITT) ............................................... 45 
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Protocol AGX-17-001-US 
Rev. C:  March 27, 2019  
7.3.3 Per Protocol Population ................................................................................ 45 
7.3.4 No TraceIT Population ................................................................................. 45 
7.3.5 Safety Population .......................................................................................... 45 
7.4 
Subgroup Analyses ........................................................................................... 45 
7.5 
Subject Disposition ........................................................................................... 45 
7.6 
Planned Analyses .............................................................................................. 45 
7.6.1 Baseline Characteristics ................................................................................ 45 
7.6.2 Technical Success, TraceIT Injection and Device Use ................................. 46 
7.6.3 Radiotherapy Benefits ................................................................................... 46 
7.6.4 Change in Baseline in Quality of Life Measures .......................................... 46 
7.6.5 Other Outcome Measures ............................................................................. 46 
7.7 
Safety Analysis ................................................................................................. 46 
7.8 
Incomplete/Missing data ................................................................................... 47 
8 
RISK/BENEFIT ANALYSIS ................................................................................... 47 
8.1 
Risk/ Benefit Analysis ...................................................................................... 47 
8.2 
Risks of Study Procedures and Investigational Material .................................. 48 
8.3 
Potential Benefits to the Subject ....................................................................... 49 
8.4 
Minimization of Risks....................................................................................... 49 
9 
ADVERSE EVENTS ................................................................................................ 50 
9.1 
Definitions......................................................................................................... 50 
9.1.1 Recording and Reporting of Adverse Events ................................................ 51 
9.1.2 Clinical Events Committee ........................................................................... 52 
9.2 
Device Malfunctions ......................................................................................... 53 
10 GENERAL INFORMATION ................................................................................... 53 
10.1 
Termination of Study ........................................................................................ 53 
10.2 
Monitoring Procedures...................................................................................... 53 
10.3 
Modifications to the Protocol............................................................................ 54 
10.4 
Protocol Violations / Deviations ....................................................................... 54 
10.5 
Financial Disclosure .......................................................................................... 54 
10.6 
Record Retention .............................................................................................. 54 
11 REFERENCES ......................................................................................................... 56 
12 APPENDICES .......................................................................................................... 58 
12.1 
APPENDIX A – AJCC PANCREAS CANCER STAGING AND ZUBROD 
PERFORMANCE SCORE SCALE ............................................................................. 58 
APPENDIX B – COMMON TERMINOLOGY CRITERIA FOR ADVERSE 
EVENTS (CTCAE) ...................................................................................................... 60 
APPENDIX C - SAMPLE INFORMED CONSENT FORM........................................65 
APPENDIX D - INVESTIGATOR AGREEMENT AND 
CERTIFICATION……......76 
 
 
 
 
 
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TraceIT Tissue Spacer (TIPS Pilot)  
 
 
 
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Protocol AGX-17-001-US 
Rev. C:  March 27, 2019  
1 
SUMMARY OF CHANGES 
 
Protocol Revision 
Protocol Section 
Description of Change 
Reason for Changes 
REV A 
(October 10, 
2017) 
N/A 
Original issue 
Original issue 
 
REV B 
(December 5, 
2017) 
Inclusion Criteria: Protocol 
Summary; Sec. 6.3.1 
f. Serum creatinine: 1.5 times ULN changed to “f. Serum 
creatinine: < 1.5 times ULN” 
Editorial Correction: 
Missing < symbol 
Clinical Events Committee 
(CEC): Protocol Summary 
Removed “in each study arm” 
Editorial Correction: Will 
only have 1 study arm 
 
Inclusion Criteria: Protocol 
Summary; Sec. 6.3.1 
2. Biopsy-confirmed BRPC and LAPC in the head or 
neck of the pancreas that is able to be visualized via CT 
or other imaging modality (e.g., PET) with no evidence of 
distant metastasis (AJCC clinical stage IIA-III): 
a. Borderline resectable pancreatic carcinoma 
disease as defined by the NCCN guidelines as 
follows 
i. SMV and portal vein: Abutment, 
encasement, or occlusion of the short 
segment of vein, 
ii. Tumor abutment ≤ 180 degrees 
iii. Celiac Axis: Uninvolved celiac axis; 
short segment encasement or abutment of 
common hepatic that may be amenable to 
resection and reconstruction 
iv. No involvement of lymph nodes 
b. Locally advanced pancreatic carcinoma disease 
as defined: 
i. Major portal vein or superior 
mesenteric artery (SMA) thrombosis, 
NCCN guidelines 
clarification based on 
TIPS investigators’ input. 
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TraceIT Tissue Spacer (TIPS Pilot)  
 
 
 
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Protocol AGX-17-001-US 
Rev. C:  March 27, 2019  
ii. Circumferential encasement of the 
SMA or 
iii. Involvement of the aorta, celiac axis 
or proximal hepatic artery.  
 
Changed to  
 
2. Biopsy-confirmed BRPC or LAPC in the head or neck 
of the pancreas that is able to be visualized via CT or 
other imaging modality (e.g., PET) with no evidence of 
distant metastasis (AJCC clinical stage IIA-III) as defined 
by the NCCN guidelines:  
 
Post-Injection RT Planning: 
Protocol Summary; Sec. 6.4.1 
Table 2 and Figure 1; Sec. 
6.4.8, ICF 
5-10 days following Index Procedure changed to “less 
than 28 days following Index Procedure” 
Window can be wider to 
accommodate patient 
convenience. RT is 
typically completed in 5 
or 6 fractions and 
therefore longer duration 
between TraceIT 
administration and RT 
planning/initiation will 
not impact TraceIT 
performance (the 
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Protocol AGX-17-001-US 
Rev. C:  March 27, 2019  
hydrogel material is 
stable for 3 months). 
Selection and Training of 
Investigators: Sec. 6.2 
Only radiation oncologists who meet the credentials … 
changed to “Only radiation oncologists and physicists 
who meet the credentials…” 
Physicists may be sub-
Investigators for this 
study 
RT Planning: Protocol 
Summary; Sec 6.4.6; Sec 7.6.3 
Changed V33 dose constraint measurement to V35 for 
proximal duodenum, proximal stomach, small bowel and 
stomach.  
Should match ongoing 
Alliance trial in same 
subject population 
Table of Contents 
Updated “REFERENCES ……………. ERROR! 
BOOKMARK NOT DEFINED.” to “REFERENCES 
…………….. 47” 
Broken link in Table of 
Contents 
Protocol Rev C 
(March 2019) 
 
 
 
 
 
 
 
 
 
 
 
 
Study Title 
EARLY FEASIBILITY STUDY FOR EVALUATION OF THE 
TRACEIT® TISSUE SPACER FOR CREATING SPACE 
BETWEEN THE DUODENUM AND PANCREAS IN PATIENTS 
WITH BORDERLINE RESECTABLE OR LOCALLY 
ADVANCED PANCREATIC CANCER UNDERGOING A 
COURSE OF SBRT 
 
Changed to  
 
EARLY FEASIBILITY STUDY FOR EVALUATION OF THE 
TRACEIT® TISSUE SPACER FOR CREATING SPACE 
BETWEEN THE DUODENUM AND PANCREAS IN PATIENTS 
WITH LOCALIZED PANCREATIC CANCER UNDERGOING 
RADIATION THERAPY 
Clarification of resectable 
pancreatic cancer patient 
population and 
radiotherapy.  
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Protocol AGX-17-001-US 
Rev. C:  March 27, 2019  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol Summary- Study 
Design 
Multicenter prospective, single-arm early feasibility 
study.  Six (6) subjects with either borderline resectable 
or locally advanced pancreatic cancer (defined per 
NCCN guidelines) having completed induction 
chemotherapy and for whom a course of SBRT is 
indicated will be enrolled 
 
Changed to  
 
Multicenter prospective, single-arm early feasibility 
study.  Six (6) subjects with localized (resectable, 
borderline resectable or locally advanced) pancreatic 
cancer (defined per NCCN guidelines) having completed 
induction chemotherapy if required and for whom a 
course of radiotherapy (RT) is indicated will be 
enrolled.  
 
Clarification of resectable 
pancreatic cancer patient 
population and 
radiotherapy. 
Protocol Summary, Protocol 
SBRT (Stereotactic body radiation therapy)  
 
Changed to  
 
RT (Radiotherapy) 
Clarification of 
radiotherapy modalities 
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Protocol AGX-17-001-US 
Rev. C:  March 27, 2019  
Inclusion Criteria: Protocol 
Summary; Sec. 6.3.1  
2. Biopsy-confirmed BRPC and LAPC in the head or 
neck of the pancreas that is able to be visualized via CT 
or other imaging modality (e.g., PET) with no evidence of 
distant metastasis (AJCC clinical stage IIA-III) as defined 
by the NCCN guidelines:  
 
Changed to  
 
2. Biopsy-confirmed localized pancreatic cancer in the 
head or neck of the pancreas that is able to be visualized 
via CT or other imaging modality (e.g., PET) with no 
evidence of distant metastasis (AJCC clinical stage IIA-
III) as defined by the NCCN guidelines:  
Clarification of resectable 
pancreatic cancer patient 
population 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Protocol AGX-17-001-US 
Rev. C:  March 27, 2019  
Inclusion Criteria: Protocol 
Summary; Sec. 6.3.1  
3. Tumor is clearly delineable from duodenum with at 
least 1 mm of space visible and no invasion of the 
duodenum is seen at time of EUS performed for either 
diagnosis or fiducial placement. 
 
Changed to  
 
3. Tumor is clearly delineable from duodenum and no 
invasion of the duodenum is seen at time of EUS 
performed for either diagnosis or fiducial placement. 
 
Precise measurements are 
difficult with current 
visualization methods 
and an identifiable 
delineation is sufficient 
for enrollment.  
Inclusion Criteria: Protocol 
Summary; Sec. 6.3.1 
5. Radiotherapy or chemoradiotherapy for treatment of 
the disease is indicated with the intent for eventual 
surgical resection 
 
Changed to 
 
5. Radiotherapy or chemoradiotherapy for treatment of 
the disease is indicated  
 
LAPC by nature cannot 
always be surgically 
resected  
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TraceIT Tissue Spacer (TIPS Pilot)  
 
 
 
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Protocol AGX-17-001-US 
Rev. C:  March 27, 2019  
Exclusion Criteria: Protocol 
Summary; Sec. 6.3.2 
4. Presence of tumor invasion detected on EUS at 
time of biopsy  
 
Changed to  
 
4. Presence of tumor invasion of the duodenum 
detected on EUS at time of biopsy  
 
Clarification of location 
of tumor invasion 
Exclusion Criteria: Protocol 
Summary; Sec. 6.3.2 
6. Active gastroduodenal ulcer or watery diarrhea 
 
Changed to  
 
6. Active gastroduodenal ulcer or uncontrolled watery 
diarrhea 
 
Clarified to 
uncontrollable watery 
diarrhea as many patients 
are on chemotherapy 
during screening which 
can cause watery 
diarrhea. 
Exclusion Criteria: Protocol 
Summary; Sec. 6.3.2 
12. Pregnancy, breast-feeding, women of child-bearing 
age must use contraceptives. 
 
Changed to 
 
12. Women who are pregnant or breast-feeding; women 
of child-bearing age must use contraceptives 
Grammatical error 
Screening/Baseline: Protocol 
Summary 
Subjects who appear to meet the eligibility criteria will be 
consented for the study and will undergo screening. 
Information to be collected at this visit includes: 
 
Changed to  
 
Subjects who appear to meet the eligibility criteria will be 
consented for the study and will undergo screening. 
Information to be collected at screening and baseline 
includes: 
Clarification that the 
screening/baseline 
assessments can be done 
over several days and not 
at one visit.  
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Protocol AGX-17-001-US 
Rev. C:  March 27, 2019  
Protocol Summary: Week 2-6 
Following Completion of RT 
(Restaging & Evaluation for 
Potential Resection at time of 
CT) 
• 
CA-19-9 level Pancreaticoduodenectomy should 
be targeted to be performed 
 
Changed to 
 
• 
CA-19-9 level  
• 
Pancreaticoduodenectomy should be targeted to 
be performed 
Typographical error 
Section 4 
Adding: 
A recent study has shown that this outcome may be 
improved by adding a pre-operative neoadjuvant 
chemoradiotherapy for resectable patients.4 Neoadjuvant 
therapy has the advantage of reducing the risk of 
developing metastatic disease in 15 to 35% of patients.5   
 
Justification to include 
resectable pancreatic 
cancer patients 
Section 4.1.1 
Adding: Pre-clinical and clinical investigational studies 
Providing new 
information available for 
the device 
Table 1: TraceIT Tissue Spacer 
– Component Descriptions 
Adding 3mL configuration option  
Equivalent material in 
larger volume, allows for 
fewer dilution steps 
Section 5 
Six (6) subjects with a biopsy confirmed diagnosis of 
BRPC or LAPC (AJCC clinical stage IIA-III) having 
completed a course of induction chemotherapy and 
indicated for image-guided radiotherapy with SBRT 
will be recruited… 
 
Changed to  
 
Six (6) subjects with biopsy confirmed localized 
pancreatic cancer (AJCC clinical stage IA-III) having 
completed a course of induction chemotherapy and 
Clarification of 
radiotherapy modalities; 
removing reference to 
stereotactic RT to make 
protocol more consistent 
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Protocol AGX-17-001-US 
Rev. C:  March 27, 2019  
indicated for image-guided radiotherapy will be 
recruited… 
Section 5 
The study will be conducted at up to 3 investigational 
sites in the United States. Duration of participation for 
subjects is approximately 21 months.   
 
 
Changed to 
 
The study will be conducted at up to 4 investigational 
sites in the United States. Duration of participation for 
subjects is approximately 22 months.   
 
Opening study to more 
sites due to lack of 
enrollment at current 
sites. Increasing the time 
for participation to 
account for longer 
fractionation schedule 
Section 6.2 
All investigators that will use the investigational device 
will undergo training per the TraceIT Tissue Spacer 
Instructions for Use prior to initial use. Additionally, 
training for injections will be performed via a cadaver lab 
and/or the use of phantoms.   
Changed to 
 
All investigators that will use the investigational device 
will undergo training per the TraceIT Tissue Spacer 
Instructions for Use prior to initial use. Additionally, 
training for injections will be performed via an animal 
lab, a cadaver lab and/or the use of phantoms.   
 
Adding additional 
appropriate method for 
Investigator training 
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Protocol AGX-17-001-US 
Rev. C:  March 27, 2019  
Section 6.4.1 
The schematic of the trial is presented in Table 2, Table 
3, and  Figure . 
Changed to  
The schematic of the trial is presented in Table 2, Table 
3, and  Figure 1. 
Typographical error 
 
Section 6.4.2 
After the informed consent has been signed, each subject 
will be entered on a screening/enrollment log, which 
will be submitted regularly to the Sponsor.  Once a 
subject is consented, a unique 5-digit subject 
identification number which includes the 2-digit site 
number plus a sequential 3-digit subject number starting 
at 001 (e.g., 01-001) will be assigned. 
 
Changed to  
Each subject will be assigned a screening number and 
will be entered on a screening log, which will be 
submitted regularly to the Sponsor. After the informed 
consent has been signed, a unique 5-digit subject 
identification number which includes the 2-digit site 
number plus a sequential 3-digit subject number starting 
at 001 (e.g., 01-001) will be assigned and subject is 
screened for eligibility criteria and considered 
enrolled in the study if all eligibility criteria is met.    
  
Clarification of 
enrollment definition 
Section 6.4.2  
A subject is considered enrolled in the study at the time 
of the informed consent.  
Changed to 
Clarification of 
enrollment definition 
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Protocol AGX-17-001-US 
Rev. C:  March 27, 2019  
A subject is considered enrolled in the study after 
screening has been completed and the subject meets 
eligibility criteria. 
Section 6.4.5.1 
The subject is to be positioned in the supine position and 
an endoscopic ultrasound (EUS) will be used to identify 
the duodenum and HOP interface.   
Changed to 
The subject is to be positioned in the left-lateral position 
and an endoscopic ultrasound (EUS) will be used to 
identify the duodenum and HOP interface.   
Standard of care for the 
fiducial procedure is 
performed in left-lateral 
position 
 
Section 6.4.6 
The technique for delivering the external beam treatment 
will employ stereotactic body radiation therapy 
(SBRT) techniques using daily image guidance. 
Changed to 
 
The technique for delivering the external beam treatment 
will be employed per institutional standard guidelines. 
Clarification of radiation 
therapy 
Section 6.4.14 
6.4.14 Additional Follow-up at Month 3 (± 14 days) and 
Month 6 (± 14 days) and Post-Index Procedure 
Changed to 
6.4.14 Additional Follow-up at Month 3 (± 14 days) and 
Month 6 (± 14 days) Post-Index Procedure 
 
Typographical error 
Section 6.4.15 
6.4.15 Longer Term Follow-Up 
Following the 6 month visit, subjects will be followed 
through to 18 months in accordance with standard of care 
Updated to match study 
flow figure 
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Protocol AGX-17-001-US 
Rev. C:  March 27, 2019  
with at minimum clinical visits performed at Month 12 
and Month 18 (± 28 days for each visit) 
Changed to 
6.4.15 Long Term Follow-Up (Month 12 and 
Month 18 ± 28 days for each visit) 
The following assessments will be performed at the 12-
and 18-Month Post-Index Procedure visit: 
• 
Physical Examination: including sitting blood 
pressure, pulse, temperature, weight, 
anticoagulation status, Zubrod Performance 
Score. 
• 
Assessment of duodenal focused Adverse Events 
documented using NCI CTCAE 
• 
Other Adverse Events per NCI CTCAE 
• 
EORTC-QLQ-C30 and QLQ-PAN26 
• 
Changes in concomitant medications used to treat 
intestinal symptoms 
 
Section 7.4 
Data may be presented separately for BRPC and LAPC 
subjects as well as resected and unresected subjects. 
Details will be provided in the statistical analysis plan 
Changed to  
Data may be presented separately for localized 
(resectable, BRPC and LAPC) subjects as well as 
resected and unresected subjects. Details will be provided 
in the statistical analysis plan 
Inclusion of resectable 
pancreatic cancer patient 
population and external 
beam radiotherapy 
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Protocol AGX-17-001-US 
Rev. C:  March 27, 2019  
Section 7.5 
The number of subjects signing the informed consent and 
the number of screening failures (consented but not 
treated subjects) and the number of secondary screening 
failures will be presented.   
Changed to 
The number of subjects signing the informed consent and 
the number of primary screening failures (consented but 
not treated subjects) and the number of secondary 
screening failures (Duodenal invasion seen at time of 
index procedure) will be presented.   
Further clarification on 
primary and secondary 
screen failures 
Section 7.7 
All adverse events occurring at the time of TraceIT 
Tissue Spacer injection or attempted injection and up 
through and including the 6 month visit will be recorded 
and listed. Thereafter, only information concerning 
duodenal toxicity or events deemed related to the 
TraceIT Tissue Spacer will be collected.  
Changed to  
All adverse events occurring at the time of initiation of 
fiducial marker placement or attempted injection and up 
through and including the 18-month visit will be 
recorded and listed. 
Further clarification on 
collection of Adverse 
Events 
Section 9.1.1 
All Adverse Events (AE) and intervening illnesses must 
be documented throughout the study.   
Changed to  
All Adverse Events (AE) must be documented throughout 
the study.   
Removing redundancy 
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Protocol AGX-17-001-US 
Rev. C:  March 27, 2019  
Section 9.1.1 
All adverse events, regardless of severity or relationship 
to investigational device, will be collected from the time 
of TraceIT hydrogel injection and through the 18-month 
visit. 
Changed to  
All adverse events, regardless of severity or relationship 
to investigational device, will be collected from the time 
of initiation of fiducial marker placement and through 
the 18-month visit. 
Further clarification of 
protocol for consistency 
Section 9.1.2 
The CEC will be charged with the following 
responsibilities: 
• 
Continuous review and validation of all adverse 
events that occur over the course of the study and the 
subsequent classification of these adverse events as 
related to the device, or procedure. 
Changed to  
The CEC will be charged with the following 
responsibilities: 
• 
Continuous review and validation of all adverse 
events that occur over the course of the study and the 
subsequent classification of these adverse events as 
related to the device, procedure, radiotherapy, or 
other. 
 
Further clarification of 
protocol for consistency 
Appendix C: Sample Informed 
Consent 
You will receive 5 treatments every other day over a 
period of about 2 weeks. 
Changed to  
Clarification of radiation 
therapy  
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Protocol AGX-17-001-US 
Rev. C:  March 27, 2019  
You will receive radiation therapy as per the 
institutional standard that will explained to you by 
your doctor. 
Appendix C: Sample Informed 
Consent 
You will receive radiation treatment for about 2 weeks. 
During this period, you will receive 5 treatments based on 
a schedule given to you by your doctor. 
Changed to  
You will receive radiation treatment for about 2 – 6 
weeks. During this period, you will receive radiation 
treatments based on a schedule given to you by your 
doctor. 
Clarification of radiation 
therapy 
Appendix C: Sample Informed 
Consent 
About 6 people will be in this study at up to 3 clinics in 
the United States. You will be in this study approximately 
1 year and 9 months beginning with your screening and 
continuing until your last study visit. 
Changed to 
About 6 people will be in this study at up to 4 clinics in 
the United States. You will be in this study approximately 
1 year and 10 months beginning with your screening and 
continuing until your last study visit. 
Opening study to more 
sites due to lack of 
enrollment at current 
sites. Increasing the time 
for participation to 
account for follow-up 
schedule 
Appendix C: Sample Informed 
Consent 
Adding to Risk section: The risks to an embryo, fetus and 
breastfeeding baby are not known at this time.  
 
Updating risk section per 
ICH E6 R2 compliance 
Appendix C: Sample Informed 
Consent 
Adding: Please indicate below whether you want us to 
notify your primary care physician or your specialist of 
your participation in this study. 
 
______ Yes, I want the study doctor to inform my primary 
care physician/specialist of my participation in this study.  
Updating consent 
document per ICH E6 R2 
compliance 
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______ No, I do not want the study doctor to inform my 
primary care physician/specialist of my participation in this 
study. 
 
Appendix C: Sample Informed 
Consent 
You will be given a copy of this consent document to 
keep. 
 
Changed to 
 
You will be given a copy of signed consent document to 
keep. 
 
Updating ICF to clarify 
that subject will be given 
a copy of the signed 
consent document 
Appendix D 
Investigator Agreement and Certification 
Moved from Page 2 to 
Appendix for ease of use 
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2 
PROTOCOL SUMMARY 
Title: 
Early Feasibility Study for Evaluation of the TraceIT Tissue Spacer for 
Creating Space Between the Duodenum and Pancreas in Patients with 
Localized Pancreatic Cancer Undergoing a Course of Radiation Therapy: 
The TIPS Pilot Study 
 
Device: 
TraceIT Tissue Spacer consists of a pre-filled glass syringe containing the 
absorbable radiopaque cross-linked polyethylene glycol (PEG) hydrogel 
spacer and a delivery mechanism (syringe and needle) packaged in a single 
use kit.  
 
Indication: 
TraceIT Tissue Spacer is a radiopaque hydrogel material intended to 
temporarily position the duodenum away from the pancreas in subjects 
undergoing RT for treatment of pancreatic cancer and in creating this space 
it is the intent of TraceIT Tissue Spacer to reduce the radiation dose 
delivered to the duodenum during radiotherapy. 
 
When used as a spacer, the TraceIT hydrogel radiographically marks the 
area for radiotherapy planning and localization. 
 
Study Objective: 
To evaluate the feasibility, radiotherapy benefits, and safety when using 
TraceIT Tissue Spacer to create space between the pancreas and duodenum.  
 
Study Design: 
Multicenter prospective, single-arm early feasibility study.  Six (6) subjects 
with localized (resectable, borderline resectable or locally advanced) 
pancreatic cancer (defined per NCCN guidelines) having completed 
induction chemotherapy if required and for whom a course of radiotherapy 
(RT) is indicated will be enrolled.  
 
Enrolled subjects will undergo placement of intrapancreatic fiducial 
markers and peri-duodenal administration of TraceIT hydrogel within the 
same endoscopic ultrasound transduodenal procedure. The hydrogel will be 
distributed in small volumes (generally ~1 to 2 mL and up to a total of 20 
mL) at several areas along the proximal portion of the duodenum in the 
areas closest to the head of the pancreas (HOP).   
 
RT simulation planning will be performed prior to and following TraceIT 
placement for evaluation and comparison of duodenal dose / dose 
distribution and to assess differences in RT dosing parameters. The pre- and 
post-TraceIT injection simulation planning will be performed using the 
identical technique and similar set-up, and with appropriate respiratory 
motion control (e.g., feedback-guided inspiratory breath-hold gating, end 
expiratory gating during free breathing or abdominal compression as 
appropriate).  
 
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In accordance with standard medical practice, within 2-6 weeks after 
completion of therapy, subjects will be restaged to determine whether they 
may progress to surgery. If surgical resection is attempted and successful, 
pathological data will be recorded within the study eCRF. 
 
All subjects will be evaluated at minimum 3 and 6 months post-TraceIT 
administration. An MR will be performed at the 6 month visit to evaluate 
for TraceIT presence.  Throughout the duration of the study, subjects will 
be clinically evaluated and assessed for duodenal adverse events using the 
grading of the NCI Common Terminology Criteria for Adverse Events 
(CTCAE v4).  Quality of life data will be collected using the EORTC QLQ-
PAN26 and QLQ-C30 questionnaires. 
 
Additional longer-term follow-up clinic visits will be performed in 
accordance with standard of care, at minimum, 12 and 18 months. 
Safety Endpoints: 
Subjects will be monitored for adverse events and radiotherapy (RT) 
toxicity (using CTCAE v4) and in particular for the safety endpoint defined 
as “TraceIT administration procedure-related events which result in a delay 
in initiation of RT” as reviewed and adjudicated by a Clinical Events 
Committee. 
 
Effectiveness 
Endpoints: 
Effectiveness endpoints of interest for this study are as follows: 
• 
Feasibility: Feasibility will be defined to be Technical Success; i.e., 
the ability to place TraceIT and create space between the duodenum 
and HOP. 
• 
Radiotherapy Benefits: Will be assessed via comparison of pre- and 
post-TraceIT administration RT plans with consideration of the 
following: ability to maintain safe duodenal dose constraints, 
percent/volume of GTV/PTV receiving prescription dose and 
overall duodenal dose/ dose distribution. 
Additional data collection will include: 
• 
Incidence of resection  
• 
Histology of duodenal tissues when resection is performed 
• 
Incidence of acute (within 3 months) and late (>3 months) duodenal 
toxicity (for unresected subjects)  
• 
Theoretical dose escalation from post-TraceIT treatment plan  
• 
TraceIT persistence (at 6-months post-treatment in nonresected 
subjects) 
• 
Change from baseline in EORTC QoL (QLQ-C30) and QLQ-
PAN26  
• 
Comparability of visualization of the fiducial marker and TraceIT 
hydrogel using a standardized visualization score 
• 
Progression free and overall survival through follow-up 
 
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Protocol AGX-17-001-US 
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Inclusion Criteria: 
 
Subjects must meet all of the following criteria to be eligible for 
participation in the study: 
 
1. Age ≥18 years old 
2. Biopsy-confirmed localized pancreatic cancer in the head or neck of 
the pancreas that is able to be visualized via CT or other imaging 
modality (e.g., PET) with no evidence of distant metastasis (AJCC 
clinical stage IA-III) as defined by the  NCCN guidelines:  
 
3. Tumor is clearly delineable from duodenum and no clear evidence 
of invasion of the duodenum is seen at time of EUS performed for 
either diagnosis or fiducial placement. 
4. Subject is able to comply with motion management guidelines 
5. Radiotherapy or chemoradiotherapy for treatment of the disease is 
indicated  
6. In Investigator’s opinion, medically fit to undergo endoscopy for 
fiducial marker implantation and TraceIT administration 
7. Subjects Screening/Baseline laboratory testing must meet the 
following laboratory value criteria: 
a. White blood cell count: ≥ 3.0 x 109/L 
b. Absolute neutrophil count (ANC): ≥ 1.5 x 109/L  
c. Platelets: ≥ 100 x 109/L 
d. Total bilirubin: ≤ 2.0 times upper limit of normal (ULN) 
e. AST and ALT: ≤ 3.0 times institutional upper normal limit 
f. Serum creatinine: < 1.5 times ULN  
g. INR: < 1.5 
h. Serum pregnancy: Negative 
i. 
Hemoglobin: ≥ 8.0 g/dl 
8. Zubrod Performance Status 0-2 
9. Subject or authorized representative, has been informed of the 
nature of the study and has provided written informed consent, 
approved by the appropriate Institutional Review Board (IRB) of 
the respective clinical site 
10. Life expectancy of at least 9 months 
 
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Protocol AGX-17-001-US 
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Exclusion Criteria 
Subjects who meet any of the following criteria are not eligible for 
participation in the study: 
 
1. Patients for whom radiotherapy is contraindicated 
2. Previous thoracic or abdominal radiotherapy 
3. Any GI abnormality that would interfere with the ability to access 
the injection site  
4. Presence of tumor invasion of the duodenum detected on EUS at 
time of biopsy  
5. Previous Whipple procedure or other resection of pancreatic tumor 
prior to screening 
6. Active gastroduodenal ulcer or uncontrolled watery diarrhea 
7. History of Chronic Renal Failure 
8. Documented history of uncontrolled diabetes (i.e., symptomatic 
hyperglycemia that cannot be medically managed, fasting blood 
glucose level above 300 mg/dL, and/or frequent swings between 
hyperglycemia and hypoglycemia) 
9. Currently enrolled in another investigational drug or device trial 
that clinically interferes with this study 
10. Unable to comply with the study requirements or follow-up 
schedule 
11. Any condition or comorbidity that the Investigator believes would 
interfere with the intent of the study or would make participation 
not in the best interest of the subject 
12. Women who are pregnant or breast-feeding; women of child-
bearing age must use contraceptives 
 
Screening/Baseline: 
(within 45 days 
prior to planned 
TraceIT hydrogel 
injection) 
Subjects who appear to meet the eligibility criteria will be consented for the 
study and will undergo screening. Information to be collected at screening 
and baseline includes: 
 
• 
Demographic information: date of birth, weight and height, race 
• 
Disease documentation: tumor location, initial resectability status, 
tumor staging, largest pre-treatment dimension of tumor (cm) 
• 
Medical/Surgical History/Current status: concomitant medical 
conditions, prior medical conditions, prior surgeries, prior therapies 
(e.g., induction chemotherapy) 
• 
Physical Examination: including sitting blood pressure, pulse, 
temperature, weight, anticoagulation status, Zubrod Performance 
Score 
• 
Laboratory testing for hematology plus platelets, creatinine, 
AST/ALT and bilirubin and baseline serum carbohydrate antigen 
(CA) 19-9 
• 
Pregnancy test for women of child-bearing potential. 
• 
EORTC-QLQ-C30 and QLQ-PAN26 
• 
Assessment of baseline duodenal symptoms per NCI CTCAE 
• 
Baseline concomitant medications 
 
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Protocol AGX-17-001-US 
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Initial RT Planning 
& Documentation  
Subjects who appear to meet the inclusion criteria and do not present with 
any of the exclusion criteria will undergo a CT for baseline RT Planning.  
 
The initial minimum target dose will be 33 Gy in 5 fractions (or an 
equivalent biologically effective dose if >5 fractions is being delivered). CT 
simulation will be performed with immobilization.  
 
Target dose constraints for OAR include: 
 
Organs at Risk 
(OAR) 
Dose Constraint* 
Proximal 
duodenum, 
proximal stomach 
and small bowel 
V15Gy<9cc, V20Gy<3 cc, and 
V35Gy<1cc 
A duodenal maximum dose of ≤32 Gy 
should initially be attempted 
Stomach  
V12Gy<50%, V35Gy<1cc 
Liver 
V12Gy<50% 
Combined Kidneys V12Gy<75%; 
Spinal Cord 
V8Gy<1 cc 
*or biologically equivalent dose constraints for >5 fractions 
 
Radiographic tumor-vessel interface will be documented. 
 
Other dosimetric data to be collected include: V5 (volume (cc) of the 
duodenum receiving 5 Gy or more), V10, V15, V20, V25, V30, V35, V40, 
duodenal mean/maximum doses, GTV/PTV minimum/mean/maximum 
doses as well as GTV/PTV volume, and total duodenal volume. 
 
Index Procedure: 
Fiducial 
Placement/ 
TraceIT Hydrogel 
Injection  
• 
Ability to access injection site and inject TraceIT material 
• 
Average duodenal space measurements on CT measured at 3 points 
along the head of the pancreas 
• 
TraceIT Injection Procedure Duration 
• 
Ease of Device Use 
• 
Device malfunctions 
• 
Adverse Events per NCI CTCAE ver. 4.0 
 
Follow-up for Non-
Injection Subjects 
(30 days +7 days or 
until resolution/ 
stabilization of an 
adverse event if 
applicable) 
A “Non-Injection” Subject is a subject who was intended to be treated with 
TraceIT, but in whom TraceIT was unable to be injected.  No further image 
collection is required for these subjects. 
• 
30 Day Visit to include: 
o Physical Assessment: including sitting blood pressure, pulse, 
temperature, and Zubrod Performance Score 
o Assessment of Intestinal Adverse Events documented using 
CTCAE criteria 
o Other Adverse Events per NCI CTCAE  
• 
Changes in concomitant medications used to treat intestinal 
symptoms 
 
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Protocol AGX-17-001-US 
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Post-injection RT 
Planning (less than 
28 days following 
Index Procedure) 
• 
Repeat CT Planning Imaging using the same number of beams and 
set-up as Pre-injection planning 
• 
Dosimetric data to be collected include: V5 (volume (cc) of the 
duodenum receiving 5 Gy or more), V10, V15, V20, V25, V30, 
V35, V40, duodenal mean/maximum doses, GTV/PTV 
minimum/mean/maximum doses as well as GTV/PTV volume, and 
total duodenal volume 
• 
Theoretical dose escalation (maximum dose to GTV while 
maintaining duodenal dose constraints) 
 
RT Initiation 
 
• RT must be initiated no later than (NLT) 28 days following TraceIT 
administration 
• RT should be initiated no sooner than (NST) 1 week from last 
chemotherapy dose 
 
Final RT Fraction 
• 
Physical Assessment (including vital signs, weight and Zubrod 
Performance score) 
• 
EORTC-QLQ-C30 and QLQ-PAN26 
• 
Assessment of duodenal focused Adverse Events documented using 
NCI CTCAE    
• 
Other Adverse Events per NCI CTCAE 
• 
Changes in concomitant medications used to treat intestinal 
symptoms 
 
Week 2-6 
Following 
Completion of RT 
(Restaging & 
Evaluation for 
Potential Resection 
at time of CT) 
• 
Physical Examination: including sitting blood pressure, pulse, 
temperature, weight, anticoagulation status, Zubrod Performance 
Score 
• 
CT for restaging (also will evaluate TraceIT Persistence) 
• 
Assessment of duodenal focused Adverse Events documented using 
NCI CTCAE    
• 
Other Adverse Events per NCI CTCAE 
• 
Changes in concomitant medications used to treat intestinal 
symptoms 
• 
CA-19-9 level  
• 
Pancreaticoduodenectomy should be targeted to be performed 
within 8 weeks after the completion of RT if applicable. 
 
Restaging and determination of resectability will be performed in 
accordance with the standard institutional practices. 
 
Resected Subjects 
(At time of 
resection) 
• 
Physical Examination: including sitting blood pressure, pulse, 
temperature, weight, anticoagulation status, Zubrod Performance 
Score  
• 
Assessment of duodenal focused Adverse Events documented using 
NCI CTCAE if available    
• 
Other Adverse Events per NCI CTCAE if available 
• 
Changes in concomitant medications used to treat intestinal 
symptoms 
 
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Resected Subjects 
(Histopathology 
record) 
• 
Incidence of complete or partial response (Path PR and Path CR) 
• 
Pathologic duodenal damage score rated by a local board-certified 
gastrointestinal surgical pathologist using the methods outlined by 
Verma et al.,1 where:  
o 1=no/minimal signs of mucosal damage: villi remain long 
and slender, epithelial cells have abundant eosinophilic 
cytoplasm with few mitotic figures, and the lamina propria 
have normal amounts of inflammatory cells including few 
or no neutrophils.  
o 2=moderate damage where villi are blunted or absent, 
epithelial cells have reactive/reparative, changes with 
basophilic cytoplasm, increase mitotic figures, and/or small 
erosions or focal ulcerations; the lamina propria show 
increased inflammation including eosinophils and 
neutrophils. 
o 3=severe damage with diffuse epithelial damage absent 
with or without extensive ulcerations and residual surviving 
epithelium displaying marked reactive/reparative changes; 
lamina propria replaced with granulation tissue and/or 
overlying fibrinoid inflammatory exudates with numerous 
neutrophils or marked damage.  
 
Additional Follow-
up at Month 3 (± 
14 days) and 
Month 6 (± 14 
days) Post-Index 
Procedure 
• 
Physical Examination: including sitting blood pressure, pulse, 
temperature, weight, anticoagulation status, Zubrod Performance 
Score 
• 
Unresected subjects only: MRI at Month 6 post-index procedure  
• 
Assessment of duodenal focused Adverse Events documented using 
NCI CTCAE    
• 
Other Adverse Events per NCI CTCAE 
• 
PAN26, EORTC-QLQ-C30 
• 
Changes in concomitant medications used to treat intestinal 
symptoms 
• 
Post-surgical complications in resected subjects  
 
Longer-Term 
Follow-up 
Following the 6-month visit, subjects will be followed through to 18 months 
in accordance with standard of care with at minimum clinical visits 
performed at Month 12 and Month 18 (± 28 days for each visit). 
 
Clinical Events 
Committee (CEC) 
A CEC will be appointed by Augmenix. Members of the CEC will include 
physicians with a specialty in treating patients with pancreatic cancer 
including a radiation oncologist and a gastroenterologist.  These physicians 
will be independent of the study Investigators and will be responsible for 
interim review and classification of adverse events observed and will 
review data related to the conduct and quality of the study. The CEC may 
make formal recommendations for protocol changes to mitigate risk of 
adverse events.  
 
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3 
PRINCIPAL CONTACTS 
 
Sponsor Contacts: 
 
 
 
Chelsea Reinhold 
 
 
 
 
 
 
Clinical Project Manager 
Augmenix, Inc. 
201 Burlington Road 
Bedford , MA 01730 
(781) 902-1624 (o) 
(781) 895-3236 (f) 
(203) 241-9779 (c) 
 
 
 
 
 
 
chelsea.reinhold@bsci.com 
 
 
 
 
 
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4 
 
INTRODUCTION 
Despite improvements in therapy, pancreatic adenocarcinoma remains a deadly disease with an 
extremely dismal prognosis. Indeed the disease is now the third leading cause of cancer-related 
death.2 The aggressive nature of this cancer is partly due to its late presentation and the intimate 
anatomic relationship between the pancreas and adjacent structures, namely the duodenum, 
stomach, liver, bile ducts, spleen, and the great vessels and their branches.3  
 
The only curative treatment for pancreatic cancer is surgical resection, most commonly by 
pancreato-duodenectomy or distal pancreatectomy (for pancreatic tail tumors). Resectable 
patients have markedly improved 5-year overall survival (OS) of approximately 20%. A recent 
study has shown that this outcome may be improved by adding a pre-operative neoadjuvant 
chemoradiotherapy for resectable patients.4 Neoadjuvant therapy has the advantage of reducing 
the risk of developing metastatic disease in 15 to 35% of patients.5 By contrast unresectable 
disease is associated with dismal 5-year OS rates of <5%. However, since the signs and 
symptoms of pancreatic cancer are not usually clinically apparent until the advanced stages, it has 
been reported that, overall, less than 20 to 25% of pancreatic tumors are amenable to resection at 
the time of diagnosis. 6,7 
 
Among patients with pancreatic cancer, a subset present with borderline resectable pancreatic 
cancer (BRPC), for which neoadjuvant therapy has an established role in obtaining a margin 
negative (R0) surgical resection and thus improving long term survival.8 Additionally, many 
patients present with locally advanced unresectable disease (LAPC) that with the proper 
neoadjuvant treatment could potentially be down-staged to resectable disease. In general, 
neoadjuvant treatment is becoming increasingly explored in hopes of improving the prognosis of 
pancreatic cancer by treating micrometastases, reducing tumor volume and increasing the 
likelihood of an R0 resection for both borderline resectable and locally advanced disease.8 
 
Thus, current guidelines for the management of patients with borderline resectable and locally 
advanced disease include single- or multi-agent chemotherapy or chemoradiation (CRT) in 
sequence with chemotherapy.7 Although results of studies comparing chemotherapy alone to 
CRT for patients with BR/LAPC have been mixed   10,11,12,13 in some series among patients with 
outright unresectable disease, 8% to 30% are converted to a resectable state following 
chemoradiotherapy. Patients with borderline resectable disease are likely to ultimately undergo 
resection, and thus there is a strong rationale for use of local therapy radiation in addition to 
chemotherapy in these patients.14 
 
The importance of local control or delaying local progression on improving morbidity and 
possibly mortality in patients with pancreatic cancer is supported by autopsy data demonstrating 
that 30% of patients die of locally destructive disease.15 It follows then that in the cases of 
BR/LAPC, advanced radiation therapy techniques using dose-escalation with intensity modulated 
radiotherapy (IMRT) and stereotactic body radiotherapy (SBRT) are potential strategies to 
improve local control. However, the tolerance of the surrounding GI tract has historically limited 
delivering higher doses of radiation therapy to the gross tumor.  
 
The majority of pancreatic tumors are in the head of the pancreas. The primary RT dose limiting 
structure for tumors in the head of the pancreas is the duodenum. The intimate relationship 
between the head of the pancreas and the duodenum puts this organ at risk for significant 
radiation toxicity, particularly in consideration that chemotherapy regimens used in conjunction 
with RT serve the purpose of increasing radiosensitivity, not just to the tumor, but normal GI 
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tissues as well. Potential complications include duodenal stricture, duodenitis, bleeding, 
obstructive jaundice, duodenal hemorrhage and diarrhea among others.16 Indeed, when delivering 
stereotactic doses of radiation in multiple fractions, as is the current convention, and when 
adhering to contemporary duodenal dose constraints, the rates of medically significant grade ≥3 
duodenal toxicity continues to be a problem reported in up to 15% of patients.17 
 
As radiation dose from stereotactic radiation drops off very quickly, displacement of the 
duodenum from the pancreas by only a few millimeters would be expected to significantly 
diminish duodenal toxicity. A similar product, SpaceOAR, was cleared by the FDA in 2015 
specifically for use to temporarily position the anterior rectal wall away from the prostate during 
radiotherapy for prostate cancer. In a prospective randomized (2:1), controlled multicenter study 
evaluating 222 men with clinical stage T1 or T2 prostate cancer, SpaceOAR use was associated 
with significant rectal dosimetric benefits and reduced rectal toxicity severity as well as a 
decrease in the proportion of patients experiencing declines in bowel quality of life. 18,19 Thus it is 
believed, that incorporation of application of the TraceIT Tissue Spacer into the regimen of 
radiotherapy treatment can allow for improvement in RT delivery in multiple aspects including: 
1) allowing for safe duodenal dose constraints to be achieved at the target prescription dose; 2) 
allow for an increase in tumor volume coverage while maintaining acceptable duodenal dose 
constraints or 3) allow for an individualized dose escalation prescription while maintaining 
acceptable duodenal dose constraints.  Space creation between the duodenum and HOP may also 
provide a benefit in reducing incidental radiation to the duodenum due to intra and interfraction 
motion. 
 
Success in any one of the parameters noted above would make TraceIT Tissue Spacer an 
important tool for the radiation oncologist as they plan and treat patients with cancer of the 
pancreatic head. 
 
4.1 
Report of Prior Investigations 
 
The TraceIT Tissue Spacer, which consists primarily of water and polyethylene glycol (PEG) is 
formulated with constituents that have a long history of safe use in implantable medical devices. 
Additionally, the materials used in the manufacture of the TraceIT Tissue Spacer have a history 
of use as FDA approved and cleared degradable implants used adjacent to sensitive tissues (e.g. 
neurological tissues) and the hydrogel material is currently commercially available to be used for 
tissue marking similar to a fiducial marker. Results of biocompatibility testing demonstrate that 
TraceIT Tissue Spacer meets the requirements specified for a permanent implant (defined as a 
device that remains implanted for greater than 30 days) as delineated in ISO 10993: Biological 
Evaluation of Medical Devices. The TraceIT Tissue Spacer has been found to meet its 
performance specifications. Once injected into the body, TraceIT Tissue Spacer has been found to 
be non-toxic, compatible with surrounding tissues and degrades within 7 months. These results 
are to be expected, since the product components (primarily water and PEG) were chosen for 
biocompatibility. The results demonstrate TraceIT Tissue Spacer hydrogel safety in clinically 
relevant models.  
 
4.1.1 Pre-Clinical and Clinical Investigations 
Pancreas-duodenum spacing was studied in human cadavers23 as a proof of concept study. Using 
the endoscopic ultrasound (EUS) approach, TraceIT Tissue Spacer was implanted in the 
pancreas-duodenum interface and adequate space was created.  The TraceIT Tissue Spacer 
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created adequate space to demonstrate dosimetric advantages, including: limiting radiation dose 
to the duodenum, enhanced coverage of the theoretical tumor and a potential for dose escalation. 
In a similar porcine study, TraceIT Tissue Spacer was also successfully placed in the pancreas-
duodenum interface using an EUS approach24. The hydrogel was clearly visible on computerized 
tomography (CT) and Cone-beam CT in all the animals that were successfully injected. A mild to 
moderate reactive inflammation isolated to the injection site was observed. Further, this porcine 
study showed that when TraceIT Tissue Spacer is injected directly into the pancreas, there was no 
evidence of pancreatitis or other adverse events. An equivalent injection was attempted into the 
duodenal wall to simulate improper injection. Though it was difficult to inject into the duodenal 
wall in the porcine model, when duodenal wall injection was successful, there was no evidence of 
local adverse events. Overall, the gel implants were tolerated well with no related adverse events.  
In a human clinical study, TraceIT hydrogel is being evaluated to access and mark the interface 
between the pancreas and duodenum using an EUS-guided approach in patients with pancreatic 
adenocarcinoma (ClinicalTrials.gov Identifier: NCT03307564). In this study, a small volume of 
hydrogel is injected to mark the interface. The visibility and safety of the hydrogel injection will 
be assessed.  
 
4.2 
Description of Investigational Device 
 
TraceIT Tissue Spacer consists of a pre-filled glass syringe containing the absorbable radiopaque 
cross-linked polyethylene glycol (PEG) hydrogel spacer and a delivery mechanism (syringe and 
needle) packaged in a single use kit.  
 
As shown in Table 1, the TraceIT Tissue Spacer consists of one prefilled glass syringe with endcap, 
one plastic receiving syringe and a luer-luer connector.  
Table 1:TraceIT Tissue Spacer -Component Descriptions 
 
Component 
Description 
Quantity 
Prefilled glass syringe 
with endcap 
 
 
A prefilled 1mL or 3mL 
glass syringe containing the 
radiopaque cross-linked 
hydrogel material with an 
endcap 
1 
Plastic receiving 
syringe 
 
 
A plastic 1mL or 3mL 
receiving syringe used to 
receive and deliver the 
radiopaque cross-linked 
hydrogel material 
1 
Luer-Luer connector 
 
 
Plastic component used to 
transfer the prefilled syringe 
material to the receiving 
syringe 
1 
 
4.3 
Indication 
 
The indication for use that will be utilized in this study is stated below. 
 
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TraceIT Tissue Spacer is a radiopaque hydrogel material intended to temporarily position the 
duodenum away from the pancreas in subjects undergoing RT for treatment of pancreatic 
cancer and in creating this space it is the intent of TraceIT Tissue Spacer to reduce the 
radiation dose delivered to the duodenum during radiotherapy. 
 
When used as a spacer, the TraceIT hydrogel radiographically marks the area for radiotherapy 
planning and localization.  
 
5 
STUDY SCOPE AND DURATION 
This is a multicenter, prospective, non-randomized, single arm, open-label early feasibility study. 
Six (6) subjects with biopsy confirmed localized pancreatic cancer (AJCC clinical stage IA-III) 
having completed a course of induction chemotherapy and indicated for image-guided 
radiotherapy will be recruited for this study and followed for a minimum of 6 months after 
injection of the TraceIT hydrogel. This visit serves as the end of the study for assessing device 
safety. Subjects will also be required to return for long-term follow-up for up to 18 months. 
 
Prior to enrollment, potential study candidates will undergo a thorough physical examination and 
documentation of medical/surgical history. A baseline Computed tomography (CT) simulation 
will be performed by Radiation Oncology department to generate a baseline RT plan. Subjects 
meeting the study eligibility criteria will undergo transduodenal injection of TraceIT Tissue 
Spacer under endoscopic ultrasound guidance performed by a participating endoscopist 
experienced with similar procedures.  As part of the subjects’ standard of care, a CT simulation 
scan will be acquired post TraceIT Tissue Spacer injection. A second radiation treatment plan 
will be generated using this CT simulation scan and the subject will begin RT for pancreatic 
cancer according to this post-injection plan. During the last fraction of RT, acute duodenal 
toxicity will be scored using CTCAE v4.0 criteria.   
 
Following the course of RT, subjects will be required to return for follow-up evaluations 2-6 
weeks after radiation therapy for a resectability assessment, followed by visits at 3, 6, 12 and 18 
months.  
 
The Sponsor will utilize a Clinical Events Committee (comprised of physicians experienced in 
treating pancreatic cancer) to provide ongoing review and adjudication of adverse events at an 
individual and aggregate level and to monitor emerging data with respect to device effectiveness. 
Any serious and/or unanticipated adverse events will be submitted for committee review within 
48 hours of the Sponsor’s receipt of notification of such events so that an evaluation of the 
risk/benefit assessment of the investigational treatment can be performed.  
 
The study will be conducted at up to 4 investigational sites in the United States. Enrollment is 
anticipated to take approximately 3 months. Duration of participation for subjects is 
approximately 22 months.   
 
6 
PROTOCOL 
6.1 
Study Objectives 
To evaluate the feasibility, radiotherapy benefits and safety when using TraceIT Tissue Spacer to 
create space between the pancreas and duodenum.  
 
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6.1.1 Safety Endpoints 
Subjects will be monitored for adverse events and RT toxicity (using CTCAE v4) and in 
particular for the safety endpoint defined as “TraceIT administration procedure-related events 
which result in a delay in initiation of RT” as reviewed and adjudicated by a Clinical Events 
Committee.  
6.1.2 Effectiveness Endpoints 
Effectiveness endpoints of interest for this study are as follows: 
 
• 
Feasibility: Feasibility will be defined to be Technical Success; i.e., the ability to place 
TraceIT and create space between the duodenum and HOP. 
• 
Radiotherapy Benefits: Will be assessed via comparison of pre- and post-TraceIT 
administration RT plans with consideration of the following: ability to maintain safe 
duodenal dose constraints, percent/volume of GTV/PTV receiving prescription dose and 
overall duodenal dose/dose distribution.  
 
6.1.3 Additional Data Collection 
Additional data collection will include but may not be limited to: 
 
• 
Incidence of resection 
• 
Progression free and overall survival 
• 
Incidence of acute (within 3 months) and late (>3 months) duodenal toxicity (for 
nonresected subjects) 
• 
Theoretical dose escalation from post-TraceIT treatment plan 
• 
TraceIT persistence (at 6-months post-treatment in nonresected subjects) 
• 
Change from baseline in EORTC QoL (QLQ-C30) and QLQ-PAN26 
• 
Comparability of visualization of the fiducial marker and TraceIT hydrogel using a 
standardized visualization score 
 
6.2 
Selection and Training of Investigators 
Only radiation oncologists and physicists who meet the credentials at their institution for planning 
and performing RT and endoscopists with prior experience with transduodenal procedures will be 
considered for participation as investigators in this study.  All investigators that will use the 
investigational device will undergo training per the TraceIT Tissue Spacer Instructions for Use 
prior to initial use. Additionally, training for injections will be performed via an animal lab, a 
cadaver lab and/or the use of phantoms.   
6.3 
Subject Selection 
6.3.1 Inclusion Criteria 
Subjects must meet all of the following criteria to be eligible for participation in the study: 
 
1. Age ≥18 years old 
2. Biopsy-confirmed localized pancreatic cancer in the head or neck of the pancreas that is 
able to be visualized via CT or other imaging modality (e.g., PET) with no evidence of 
distant metastasis (AJCC clinical stage IA-III) as defined by the NCCN guidelines:  
 
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3. Tumor is clearly delineable from duodenum and no clear evidence of invasion of the 
duodenum is seen at time of EUS performed for either diagnosis or fiducial placement. 
4. Subject is able to comply with motion management guidelines. 
5. Radiotherapy or chemoradiotherapy for treatment of the disease is indicated.  
6. In Investigator’s opinion, medically fit to undergo endoscopy for fiducial marker 
implantation and TraceIT administration. 
7. Subjects Screening/Baseline laboratory testing must meet the following laboratory value 
criteria: 
a. White blood cell count: ≥ 3.0 x 109/L 
b. Absolute neutrophil count (ANC): ≥ 1.5 x 109/L  
c. Platelets: ≥ 100 x 109/L 
d. Total bilirubin: ≤ 2.0 times upper limit of normal (ULN) 
e. AST and ALT: ≤ 3.0 times institutional upper normal limit 
f. Serum creatinine: < 1.5 times ULN e 
g. INR: < 1.5 
h. Serum pregnancy: Negative 
i. 
Hemoglobin: ≥ 8.0 g/dl 
8. Zubrod Performance Status 0-2 
9. Subject or authorized representative, has been informed of the nature of the study and has 
provided written informed consent, approved by the appropriate Institutional Review 
Board (IRB) of the respective clinical site. 
10. Life expectancy of at least 9 months 
 
6.3.2 Exclusion Criteria 
Subjects who meet any of the following criteria are not eligible for participation in the study: 
 
1. Patients for whom radiotherapy is contraindicated 
2. Previous thoracic or abdominal radiotherapy 
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3. Any GI abnormality that would interfere with the ability to access the injection site  
4. Presence of tumor invasion of the duodenum detected on EUS at time of biopsy  
5. Previous Whipple procedure or other resection of pancreatic tumor prior to screening 
6. Active gastroduodenal ulcer or uncontrolled watery diarrhea 
7. History of Chronic Renal Failure. 
8. Documented history of uncontrolled diabetes (i.e., symptomatic hyperglycemia that 
cannot be medically managed, fasting blood glucose level above 300 mg/dL, and/or 
frequent swings between hyperglycemia and hypoglycemia) 
9. Currently enrolled in another investigational drug or device trial that clinically interferes 
with this study. 
10. Unable to comply with the study requirements or follow-up schedule. 
11. Any condition or comorbidity that the Investigator believes would interfere with the 
intent of the study or would make participation not in the best interest of the subject. 
12. Women who are pregnant or breast-feeding; women of child-bearing age must use 
contraceptives
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6.4 
Study Procedures and Data Collection 
6.4.1 Study Schematics 
The schematic of the trial is presented in Table 2, Table 3, and  Figure 1 
 
Table 2:  Study Protocol Synopsis for Subjects Injected with TraceIT Tissue Spacer 
End of regulatory phase 
a Including date of birth, weight and height, race 
b Concomitant medical conditions, prior medical conditions, prior surgeries, prior therapies (e.g., induction chemotherapy)  
c Including sitting blood pressure, pulse, temperature, weight, anticoagulation status, Zubrod Performance Score 
d Including hematology plus platelets, creatinine, AST/ALT and bilirubin and baseline serum carbohydrate antigen (CA) 19-9 
e Including tumor location, initial resectability status, tumor staging, largest pre-treatment dimension of tumor (cm) 
 
 
 
 
Procedure 
Regulatory Phase: For Assessment of TraceIT Tissue Spacer Safety and Feasibility  
Screeni
ng/ 
Baseline 
Assessm
ent 
(within 
45 days 
prior to 
planned 
TraceIT 
hydrogel 
injection
) 
Initial RT 
Planning 
and 
Document
ation 
Index 
Procedu
re 
(Fiducial 
placemen
t/TraceIT 
injection) 
 
Post TraceIT 
injection RT 
Planning (less 
than 28 days after 
Index Procedure) 
Fina
l RT 
Frac
tion 
 
Week 2-6 
Following 
completio
n of RT 
(Restaging 
& 
Evaluatio
n for 
Potential 
Resection) 
Resect
ed 
Subjec
ts (at 
time of 
resecti
on) 
Additional 
Follow-up at 
3M, 6M, 
12M and 
18M Post 
Injection 
Demographic 
information a 
 
 
 
 
 
 
 
 
Med./Surg. 
History/Current statusb 
 
 
 
 
 
 
 
 
Physical Examc   
 
 
 
 
 
 
 
 
Laboratory Testing 
d 
 
 
 
 
 
 
 
Disease 
documentatione 
 
 
 
 
 
 
 
 
Pregnancy test for 
women of child 
bearing age 
 
 
 
 
 
 
 
 
EORTC-QLQ-C30, 
QLQ-PAN26 
 
 
 
 
 
 
 
 
CT Scan  
 
 
 
 
With visibility 
scoring 
 
  
 
 
MRI  
 
 
 
 
 
 
 
 (Month 6, 
unresected 
subjects only) 
Assessment duodenal 
symptoms (per NCI 
CTCAE) 
 
 
 
 
 
 
 
 
 
Concomitant Meds 
 
 
 
 
 
 
 
 
Adverse Events (per 
NCI CTCAE) 
 
 
 
 
 
 
 
 
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Table 3:  Study Protocol Synopsis for Non-Injection Subjects 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a Including date of birth, weight and height, race 
b Concomitant medical conditions, prior medical conditions, prior surgeries, prior therapies (e.g., induction chemotherapy)  
c Including sitting blood pressure, pulse, temperature, weight, anticoagulation status, Zubrod Performance Score 
d Including hematology plus platelets, creatinine, AST/ALT and bilirubin and baseline serum carbohydrate antigen (CA) 19-9 
e Including tumor location, initial resectability status, tumor staging, largest pre-treatment dimension of tumor (cm) 
 
 
 
 
 
 
Procedure 
Regulatory Phase: For Assessment of TraceIT Tissue Spacer Safety 
and Feasibility 
Screening/ 
Baseline 
Assessment 
(within 45 days 
prior to planned 
TraceIT hydrogel 
injection) 
Initial RT 
Planning 
and 
Document
ation 
Index 
Procedure 
(Fiducial 
placement/Trac
eIT injection) 
 
30 Days 
following Index 
Procedure (+7 
days or until 
resolution/ 
stabilization of an 
adverse event if 
applicable) 
Demographic 
information a 
 
 
 
 
Med./Surg. 
History/Current 
statusb 
 
 
 
 
Physical Examc   
 
 
 
 
Laboratory Testing 
d 
 
 
 
Disease 
documentatione 
 
 
 
 
Pregnancy test for 
women of child 
bearing age 
 
 
 
 
PAN26, EORTC-
QLQ-C30 
 
 
 
 
CT Scan  
 
 
 
 
MRI  
 
 
 
 
Assessment duodenal 
symptoms (per NCI 
CTCAE) 
 
 
 
 
 
 
Concomitant Meds 
 
 
 
 
Adverse Events (per 
NCI CTCAE) 
 
 
 
 
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 Figure 1: Study Procedural Flow Chart
Prescreening and Consent 
Patient agrees to participate and signs 
Informed Consent 
 
Screening/Baseline Assessments 
Demographics, Disease Documentation, Medical/Surgical history, Physical 
Exam, Zubrod Score, Laboratory Testing, CA-19-9, Pregnancy Test, EORTC-
QLQ-C30 and QLQ-PAN26 Questionnaires, Pre-existing duodenal 
symptoms, Concomitant medications
Index Procedure: 
Fiducial Placement/
TraceIT Hydrogel Injection
Subject is a Non-Injection Patient
 (Follow for 30 days + 7 days or until resolution/
stabilization of an adverse event if applicable)
Repeat CT for Post-Injection RT Planning 
(Less than 28 days following Index Procedure)
RT Treatment
CT for Restaging 
(Week 2-6)
SURGERY PLANNED?
YES
RESECTED
YES
Physical Examination, 
Zubrod Score, Duodenal 
Focused/Other Adverse 
Events, Changes in 
Concomitant Medications 
Used to Treat Intestinal 
Symptoms, Histopathology 
of Resected Tissue & 
Pathologic Duodenal 
Damage Score
NO
MONTH 3 AND 6 (+ 14 DAYS)
Physical Exam, Current Status (inc. assessment for disease progression), Duodenal 
Focused/Other Adverse Events, EORTC-QLQ-C30 and QLQ-PAN26 Questionnaires, 
Changes in Concomitant Medications Used to Treat Intestinal Symptoms 
MRI at 6 months for Unresected Subjects only
Post-Surgical Complications in Resected Subjects 
MONTH 12 AND 18 (+ 28 DAYS)
Physical Exam, Current Status (inc. assessment for disease progression), Duodenal 
Focused/Other Adverse Events, EORTC-QLQ-C30 and QLQ-PAN26 Questionnaires, 
Changes in Concomitant Medications Used to Treat Intestinal Symptoms
Post-Surgical Complications in Resected Subjects
Baseline CT for Initial RT 
Planning and Documentation
REGULATORY 
PHASE END
LONGER 
TERM 
FOLLOW UP 
FOR DISEASE 
PROGRESSION
/SURVIVAL
SUBJECT MEETS 
CRITERIA?
Screen Failure: No 
further study 
activities
YES
YES
(Enrolled)
YES/NO
NO
 
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6.4.2 Subject Enrollment 
Prior to enrollment in the study, subjects will be evaluated to determine eligibility. The subject’s 
willingness and ability to meet the follow-up requirements will be determined. If the subject 
desires to participate in the study, written informed consent will be obtained prior to performance 
of any study-specific examinations (see Section 6.4.3). Each subject will be assigned a screening 
number and will be entered on a screening log, which will be submitted regularly to the Sponsor. 
After the informed consent has been signed, a unique 5-digit subject identification number which 
includes the 2-digit site number plus a sequential 3-digit subject number starting at 001 (e.g., 01-
001) will be assigned and subject is screened for eligibility criteria and considered enrolled in the 
study if all eligibility criteria is met. No two subjects will have the same five-digit subject 
identification number.  This subject identification number will identify the subject throughout the 
study and will be used for all source documents and CRFs. Subjects who meet the eligibility 
criteria and agree to participate will be scheduled for TraceIT Tissue Spacer injection and fiducial 
marker placement. 
 
A subject is considered enrolled in the study after the subject meets eligibility criteria. Only 
subjects who undergo TraceIT Tissue spacer injection attempt (i.e., at the time the needle is 
inserted through the duodenum) will be included in the safety/effectiveness populations for 
analysis. All subjects enrolled in the study will be required to adhere to the follow-up schedule 
outlined in this protocol.  Subjects withdrawing consent after treatment will not be required to 
undergo follow-up after withdrawal; however, these participants will still be considered part of 
the study cohort and included in the safety analysis.   
 
6.4.3 Informed Consent 
All subjects considered for enrollment in the study must complete an IRB approved informed 
consent PRIOR to any study-specific procedures being performed.  The Investigator should 
adhere to GCP and to the ethical principles as delineated in 21 CFR Part 50.  Failure to obtain a 
signed informed consent renders the subject ineligible for the study. Subjects must be willing to 
undergo transduodenal placement of fiducial markers and the TraceIT Tissue Spacer and must be 
willing to consent to study procedures and return for follow-up visits upon completion of RT.   
 
6.4.4 Screening/Baseline Assessments (within 45 days prior to planned TraceIT 
hydrogel injection) 
Subjects who appear to meet the eligibility criteria will be consented for the study and will 
undergo screening. Information to be collected at this visit includes: 
• 
Demographic information: date of birth, weight and height, race 
• 
Disease documentation: tumor location, initial resectability status, tumor staging, largest 
pre-treatment dimension of tumor (cm) 
• 
Medical/Surgical History/Current status: concomitant medical conditions, prior medical 
conditions, prior surgeries, prior therapies (e.g., induction chemotherapy) 
• 
Physical Examination: including sitting blood pressure, pulse, temperature, weight, 
anticoagulation status, Zubrod Performance Score  
• 
Laboratory testing for hematology plus platelets, creatinine, AST/ALT and bilirubin and 
baseline serum carbohydrate antigen (CA) 19-9 
• 
Pregnancy test for women of child-bearing potential 
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• 
EORTC-QLQ-C30 and QLQ-PAN26 
• 
Assessment of baseline duodenal symptoms per NCI CTCAE 
• 
Baseline concomitant medications 
 
6.4.5 Fiducial Placement and TraceIT Tissue Spacer Injection  
 
6.4.5.1 Injection 
The TraceIT Tissue Spacer is to be injected between the pancreas and the duodenum by the 
participating study physician using a transduodenal approach and with endoscopic ultrasound 
(EUS) guidance as depicted in Figure 2. 
 
An EUS assessment of the space between the pancreas and the duodenum before and after 
injection is to be performed.  The following information will be collected: 
 
• 
Ability to access injection site and inject TraceIT material 
• 
Average duodenal space measurements on CT measured at 3 points along the head of the 
pancreas 
• 
TraceIT Injection Procedure Duration 
• 
Ease of Device Use 
• 
Device malfunctions 
• 
Adverse Events per NCI CTCAE ver. 4.0 
 
Figure 2: TraceIT Tissue Spacer Injection into Periduodenal Space using 
Endoscopic Ultrasound Guidance (Rao et al, used with permission) 
 
 
The subject is to be positioned in the left-lateral position and an endoscopic ultrasound (EUS) 
will be used to identify the duodenum and HOP interface.   
Under EUS guidance, the 19 or 22G fine needle aspiration (FNA) needle will be guided through 
the EUS scope and into the potential space between the duodenum and pancreas. The TraceIT 
Tissue Spacer will be prepared per the supplied IFU. Once the needle has been confirmed to be in 
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the proper position, the TraceIT hydrogel will be injected in 1mL increments. This process will 
then be repeated as the needle is repositioned around the target region, injecting TraceIT hydrogel 
at each location to a total volume of up to 20 mL hydrogel (40 mL of diluted TraceIT hydrogel in 
a 1:1 ratio).   
o Note:  If the needle is inserted through the duodenum, but the TraceIT Tissue 
Spacer is not injected, the subject will be followed for 30 days and included in the 
safety analysis.  No further imaging is required for these “non-injection” subjects. 
 
Following injection of the TraceIT hydrogel, the needle is to be removed, EUS images are to be 
acquired and measurements obtained as described above.   
 
The lot number of the TraceIT Tissue Spacer device(s) used, the number and timing of 
applications is to be recorded on the TraceIT Tissue Spacer Injection CRF. 
 
The subject should be assessed for adverse events during the follow-up period following the 
TraceIT Tissue Spacer injection. 
 
6.4.5.2 Post-Injection CT Scan Acquisition 
Following the TraceIT hydrogel injection, each subject is to undergo a repeat planning simulation 
scan to obtain a second RT radiation computer treatment plan with the TraceIT Tissue Spacer in 
situ.  
 
The first and second RT treatment plans (pre- and post-TraceIT Tissue Spacer injection) will be 
compared to evaluate the displacing properties of the TraceIT Tissue Spacer.  
 
6.4.6 RT Planning and Radiation Treatment 
The technique for delivering the external beam treatment will be employed per institutional 
standard guidelines. Identical treatment planning studies will be performed both before (pre-
TraceIT) and after (post-TraceIT) hydrogel injection in each subject.  The technique and setup for 
these two simulation studies should be nearly identical particularly with respect to patient 
immobilization and respiratory motion management (i.e., active breath-hold method, forced 
shallow breathing with abdominal compression or real-time tracking and/or gating) and beam 
arrangement and angle. Planning set-up/parameters for the pre- and Post-injection RT planning 
will be documented within the CRF.  
The initial minimum target dose will be 33 Gy in 5 fractions (6.6 Gy per fraction) or an 
equivalent biologically effective dose if >5 fractions is being delivered. The goal should be that at 
that the V33Gy for the PTV be at least 95%. CT simulation will be performed with 
immobilization when possible.  
 
Normal tissue contours will be performed in accordance with the Upper Abdominal Normal 
Organ Contouring Guidelines recommended by the 2013 RTOG Consensus Panel.  
 
Target dose constraints for OAR include: 
 
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Organs at Risk 
(OAR) 
Dose Constraint* 
Proximal 
duodenum, 
proximal stomach 
and small bowel 
V15Gy<9cc, V20Gy<3 cc, and 
V35Gy<1cc 
A duodenal maximum dose of ≤32 Gy 
should initially be attempted 
Stomach  
V12Gy<50% and V35Gy<1cc 
Liver 
V12Gy<50% 
Combined Kidneys V12Gy<75%; 
Spinal Cord 
V8Gy<1 cc 
*or biologically equivalent dose constraints for >5 fractions 
 
Target coverage, doses to OAR, dose conformity, mean and maximum proximal duodenal dose 
and dose volume histograms will be documented pre- and post-TraceIT Injection. 
 
6.4.7 Follow-up for Non-Injection Subjects (30 days +7 days or until 
resolution/stabilization of an adverse event if applicable) 
A “Non-Injection” Subject is a subject who was intended to be treated with TraceIT, but in whom 
TraceIT was unable to be injected. No further image collection is required for these subjects. 
• 
30 Day Visit to include: 
o Physical assessment: including sitting blood pressure, pulse, temperature and 
Zubrod Performance Score 
o Assessment of Intestinal Adverse Events documented using CTCAE criteria 
o Other Adverse Events per NCI CTCAE 
o Changes in concomitant medications used to treat intestinal symptoms 
 
6.4.8 Post-injection RT Planning (less than 28 days following Index Procedure) 
The following assessments will be performed during the post-injection RT planning: 
• 
Repeat CT Planning Imaging using the same number of beams and set-up as Pre-injection 
planning 
• 
Dosimetric data to be collected include: V5 (volume (cc) of the duodenum receiving 5 Gy 
or more), V10, V15, V20, V25, V30, V35, V40, duodenal mean/maximum doses, 
GTV/PTV minimum/mean/maximum doses as well as GTV/PTV volume, and total 
duodenal volume. 
• 
Theoretical dose escalation (maximum dose to GTV while maintaining duodenal dose 
constraints) 
• 
TraceIT Hydrogel and Fiducial Visibility Scoring: Visibility of the TraceIT hydrogel and 
the fiducial markers will be scored as follows: 1 – not visualized; 2 – faint or trace 
visibility (shadow or haze); 3 – visibility but indistinct borders (definable entity, not just 
haze); 4 – partially distinct border, partial haze; and 5 – clearly visualized, unequivocal. 
 
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6.4.9 RT Initiation 
RT must be initiated NLT 28 days following TraceIT administration. RT should be initiated NST 
1 week from last chemotherapy dose. At the initiation of each fraction, the appearance of the 
TraceIT hydrogel with respect to presence and material distribution should be compared to RT 
planning CT.   
 
6.4.10 Final RT Fraction 
The following assessments are to be performed at the final RT fraction: 
 
• 
Physical Assessment (including vital signs, weight and Zubrod performance score) 
• 
EORTC-QLQ-C30 and QLQ-PAN26 
• 
Assessment of duodenal focused Adverse Events documented using NCI CTCAE 
• 
Other Adverse Events per NCI CTCAE 
• 
Changes in concomitant medications used to treat intestinal symptoms 
 
6.4.11 Week 2-6 Following Completion of RT (Restaging & Evaluation for Potential 
Resection) 
The following assessments are to be performed at week 2-6 following completion of RT 
(Restaging and Evaluation for Potential Resection). These assessments can be performed at the 
time the subject returns for the restaging CT: 
 
• 
Physical Examination: including sitting blood pressure, pulse, temperature, weight, 
anticoagulation status, Zubrod Performance Score.  
• 
CT for restaging (also will evaluate TraceIT Persistence) 
• 
Assessment of duodenal focused Adverse Events documented using NCI CTCAE    
• 
Other Adverse Events per NCI CTCAE 
• 
Changes in concomitant medications used to treat intestinal symptoms 
• 
CA-19-9 level  
• 
Pancreaticoduodenectomy should be targeted to be performed within 8 weeks after the 
completion of RT if applicable. 
Restaging and determination of resectability will be performed in accordance with the standard 
institutional practices. 
 
CT’s will be reviewed by a radiologist and any radiological findings suggestive of duodenal 
injury shall be documented and graded when possible. Duodenal perforation would be suspected 
if there is a retroperitoneal collection of extraluminal gas or a lack of continuity of the duodenal 
wall. Duodenal erosion/ulceration is suspected with edema or hematoma of the duodenal wall, 
intramural gas accumulations, and focal duodenal wall thickening (>4 mm) as findings of small 
bowel injury.  
 
6.4.12 Resected Subjects (at time of resection) 
The following assessments are to be performed at time of resection: 
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• 
Physical Examination: including sitting blood pressure, pulse, temperature, weight, 
anticoagulation status, Zubrod Performance Score.  
• 
Assessment of duodenal focused Adverse Events documented using NCI CTCAE if 
available    
• 
Other Adverse Events per NCI CTCAE if available 
• 
Changes in concomitant medications used to treat intestinal symptoms 
 
6.4.13 Resected Subjects (Histopathology record) 
The following assessments are to be performed at time of histopathology: 
• 
Incidence of complete or partial response (Path PR and Path CR) 
• 
Pathologic duodenal damage score rated by a local board-certified gastrointestinal 
surgical pathologist using the methods outlined by Verma et al.,1 where:  
 
o 1=no/minimal signs of mucosal damage: villi remain long and slender, epithelial 
cells have abundant eosinophilic cytoplasm with few mitotic figures, and the 
lamina propria have normal amounts of inflammatory cells including few or no 
neutrophils.  
o 2=moderate damage where villi are blunted or absent, epithelial cells have 
reactive/reparative, changes with basophilic cytoplasm, increase mitotic figures, 
and/or small erosions or focal ulcerations; the lamina propria show increased 
inflammation including eosinophils and neutrophils. 
o 3=severe damage with diffuse epithelial damage absent with or without extensive 
ulcerations and residual surviving epithelium displaying marked 
reactive/reparative changes; lamina propria replaced with granulation tissue 
and/or overlying fibrinoid inflammatory exudates with numerous neutrophils or 
marked damage. 
 
6.4.14 Additional Follow-up at Month 3 (± 14 days) and Month 6 (± 14 days) Post-
Index Procedure 
The following assessments will be performed at the 3 and 6 Month Post-Index Procedure visit: 
• 
Physical Examination: including sitting blood pressure, pulse, temperature, weight, 
anticoagulation status, Zubrod Performance Score.  
• 
Unresected subjects only: MRI at Month 6 post-index procedure  
• 
Assessment of duodenal focused Adverse Events documented using NCI CTCAE    
• 
Other Adverse Events per NCI CTCAE 
• 
EORTC-QLQ-C30 and QLQ-PAN26 
• 
Changes in concomitant medications used to treat intestinal symptoms 
• Post-surgical complications in resected subjects 
 
6.4.15 Long Term Follow-Up (Month 12 ± 28 days and Month 18 ± 28 days) 
The following assessments will be performed at the 12- and 18-Month Post-Index Procedure 
visit: 
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• 
Physical Examination: including sitting blood pressure, pulse, temperature, weight, 
anticoagulation status, Zubrod Performance Score.  
• 
Assessment of duodenal focused Adverse Events documented using NCI CTCAE    
• 
Other Adverse Events per NCI CTCAE 
• 
EORTC-QLQ-C30 and QLQ-PAN26 
• 
Changes in concomitant medications used to treat intestinal symptoms 
 
6.5 
Subject Withdrawal 
For any subject who withdraws their consent following enrollment, the reason(s) for withdrawal 
will be documented on the appropriate CRF. In the event that a study subject does not finish their 
course of RT, the subject should be followed through 6 months from the date of the TraceIT 
hydrogel injection, whichever occurs sooner. For these subjects, participation will be concluded 
at that time and the subject will not participate in the longer-term toxicity assessment phase. 
Every attempt will be made to contact subjects who are non-compliant or lost to follow-up, and 
such attempts will be documented in the subject’s study record. 
Subjects may be replaced at the discretion of the Sponsor.   
 
7 
STATISTICAL ANALYSIS 
7.1 
Sample Size Determination 
No formal hypothesis or sample size estimation has been established since this is an early 
feasibility study with an intent to collect information concerning the procedural characteristics 
and safety for TraceIT administration within the peri-duodenal space. Six (6) subjects should 
provide sufficient experience to allow for evaluation of procedural safety and to estimate the 
impact of space creation on duodenal radiation doses.  
7.2 
General 
The statistical analysis of the data obtained from this study will be performed using SAS® Version 
9.3 or higher.    
 
All data collected in this study will be documented using summary tables and subject data 
listings. Continuous variables will be summarized using descriptive statistics, specifically the 
mean, median, standard deviation, minimum and maximum. Categorical variables will be 
summarized by frequencies and percentages.  
 
Changes from baseline in dosimetric parameters and quality of life parameters will be assessed 
using a paired t-test or, if not normally distributed, the nonparametric Wilcoxon Signed-Rank test 
for continuous variables and Chi-Square and/or McNemar’s test for dichotomous variables. 
Nominal p-values associated with statistical tests will be reported, but no significance level will 
be assigned to the values. No adjustments to nominal p-values are planned since this is a 
hypothesis-generating study. 
 
A detailed statistical analysis plan will be developed and finalized prior to database lock. 
 
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7.3 
Analysis Populations 
 
7.3.1 Intent-to-Treat Population (ITT) 
All enrolled (consented) subjects for whom TraceIT administration is attempted. This will be the 
primary analysis population for evaluation of feasibility (i.e., technical success defined as the 
ability to place TraceIT and create space between the duodenum and HOP). 
7.3.2 Modified Intent-to-Treat Population (MITT) 
All subjects enrolled in the study and who are a Technical Success will be included in the 
Modified Intent-to-Treat population. This will be the primary analysis population for purposes of 
non-safety outcome data. 
7.3.3 Per Protocol Population 
The Per Protocol (PP) Population is defined to be all subjects in the MITT population with no 
major protocol deviations that have the potential to affect the study outcomes. 
7.3.4 No TraceIT Population 
Subjects who were enrolled (consented) and for whom TraceIT administration was not 
technically successful (either hydrogel placement was abandoned due to clinical issues or no 
space created in the duodenal/pancreatic interface). 
7.3.5 Safety Population 
The Safety Population is defined to be all subjects for whom TraceIT administration is attempted 
(whether or not administration was successful). For the purposes of this study, the Safety 
Population is the same as the ITT Population.  
7.4 
Subgroup Analyses 
Data may be presented separately for localized (resectable, BRPC and LAPC) subjects as well as 
resected and unresected subjects. Details will be provided in the statistical analysis plan. 
7.5 
Subject Disposition 
The number and percentage of enrolled (ITT Population), MITT, PP and Safety Populations will 
be summarized. The number of subjects signing the informed consent and the number of primary 
screening failures (consented but not treated subjects) and the number of secondary screening 
failures (Duodenal invasion seen at time of index procedure) will be presented.  The number and 
percentage of non-injection TraceIT subjects will be presented along with the reason they were 
not able to be injected. The number and percentage of treated subjects who do not complete the 
study will be presented, along with the reason for early termination/withdrawal. Subject 
accountability by investigative site and by study visit will also be presented.  
7.6 
Planned Analyses 
7.6.1 Baseline Characteristics 
Subjects will be summarized with respect to baseline demographics and clinical characteristics 
(e.g., age, sex, tumor grade, etc.). These will be summarized by descriptive statistics including 
means, medians, standard deviations and ranges (for quantitative variables) and percentages (for 
categorical variables). 
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7.6.2 Technical Success, TraceIT Injection and Device Use 
Summary statistics will be presented for characteristics of TraceIT injection using descriptive 
statistics or counts and percentages, as appropriate. In addition, the proportion of TraceIT treated 
subjects in whom Technical Success has been achieved will be reported, together with an exact 
(Clopper-Pearson) 95% confidence interval for the true proportion. Technical Success is defined 
as the administration and visualization (on post-injection CT) of the TraceIT hydrogel between 
the head of pancreas and the duodenum.  
 
Ease of device use and preparation, and whether any device malfunctions occurred will be 
summarized by counts and percentages. Details of device malfunctions will be presented in a 
listing. 
7.6.3 Radiotherapy Benefits 
Treatment planning will be performed as a component of the Baseline Assessment and repeated 
following TraceIT administration. For both scans, summary descriptive statistics will be 
presented by assessment (i.e., Pre vs. Post TraceIT Administration) for all target volume and dose 
constraint measurements. For the post-TraceIT procedure data, the relative reduction from 
baseline in dose (V15, V20, V35, mean and maximum duodenal dose, etc.) to the duodenum will 
also be calculated and summarized. For continuous variables, the paired sample t-test will be used 
to test for a difference in means between treatment plans.  
7.6.4 Change in Baseline in Quality of Life Measures 
Changes in Quality of Life Measures as assessed overall and subdomains of the EORTC-QLQ-
C30 and QLQ-PAN26 will be evaluated. Raw scores and change from baseline scores will be 
calculated for all domains. Scores will be compared to baseline using either a paired t-test or 
Wilcoxon Signed-Rank test. 
7.6.5 Other Outcome Measures 
All other measures as identified in Section 6.1.3 not described above will be evaluated in 
accordance with the general statistical methods previously identified. The following definitions 
will be used for PFS and OS: 
• 
Progression-Free Survival (PFS): defined as the interval between the start of induction 
chemotherapy (prior to RT) to treatment failure (local, regional or distant progression) or 
death (in months). 
• 
Overall Survival (OS): defined as the interval between the start of induction 
chemotherapy (prior to RT) to death (in months). 
7.7 
Safety Analysis 
Incidence of adverse events will be summarized by body system and preferred term in accordance 
with NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0 (NCI, Oct 2009) for 
severity and/or MedDRA term.  The incidence of adverse events will be summarized by term, by 
term and procedure/device relationship, and by term and severity. All adverse events occurring at 
the time of initiation of fiducial marker placement or attempted injection and up through and 
including the 18 month visit will be recorded and listed. In addition to the general presentation of 
safety events, the following will be calculated and reported: 
• 
The number and percentage of subjects who experience TraceIT administration 
procedure-related events which result in a delay in initiation of RT.  
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• 
The number and percentage of subjects with at least one duodenal adverse event 
presented by grade and timing; i.e., acute (within 3 months) and late (>3months). A 
similar presentation will be provided for non-resected subjects only. 
 
7.8 
Incomplete/Missing data 
All practical monitoring and follow-up steps will be taken to ensure complete and accurate data 
collection. Due to the fact that subjects are undergoing therapy consistent with standard medical 
practices, it is anticipated that there will be minimal missing data. There will be no imputation of 
missing data. 
 
8 
RISK/BENEFIT ANALYSIS 
8.1 
Risk/ Benefit Analysis 
Radiation therapy is a common component of treatment for pancreatic cancer. However, due to 
the pancreas’ anatomic proximity to the duodenum, duodenal radiation injury is a risk of 
radiotherapy. Indeed, when delivering stereotactic doses of radiation in multiple fractions, as is 
the current convention, and when adhering to contemporary duodenal dose constraints, the rates 
of medically significant grade ≥3 duodenal toxicity continues to be a problem reported in up to 
15% of patients17. Since the risk of developing duodenal complications increases exponentially as 
greater volumes are irradiated, it is understandable that clinicians are seeking technologies that 
can reduce duodenal radiation dose to minimize the risk of duodenal injury associated with 
radiation therapy and maximize the tumor coverage.  
 
Based upon the results of the preclinical investigations and validated through clinical use, PEG-
based hydrogels have been shown to be safe in multiple tissue types including sensitive 
neurological and intra-abdominal tissues. The transduodenal injection procedure used for 
administration of the TraceIT hydrogel is commonly performed by endoscopists for the 
performance of pancreatic biopsies and the delivery of fiducial markers. Moreover, Augmenix in 
conjunction with researchers at John Hopkins Medical Center has performed a cadaver study 
demonstrating that creation of space between the duodenum and pancreas can substantially 
reduce the level of duodenal radiation exposure while maintaining or in some cases even 
improving PTV coverage, having a positive impact for both the reduction in duodenal toxicity 
and maximizing effects of RT on the tumor.  Conversely, there is no information in the preclinical 
data to suggest that the hydrogel material or the methods used for administration present the 
potential for significant harm when used as intended.   
 
Therefore, TraceIT hydrogel when used to displace the duodenum from the pancreas may provide 
a substantial clinical benefit as a duodenal-sparing technology that allows for a reduction in 
duodenal radiation dose and improvement in PTV coverage in patients undergoing radiotherapy 
for pancreatic cancer. It is acknowledged, however, that as with any medical procedure and 
implanted material there are risks associated with the use and administration of the TraceIT 
hydrogel.  Based on the clinical knowledge for the device’s application and preclinical study 
outcomes, potential risks associated with the hydrogel have been identified (outlined below). 
Risks have been mitigated to the extent possible, providing a favorable risk/benefit profile for the 
TraceIT Tissue Spacer. 
 
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8.2 
Risks of Study Procedures and Investigational Material 
The associated risks and potential benefits of the procedure and the device are provided below.   
 
Risks associated with radiation therapy of the pancreas 
The following risks are associated with radiation therapy of the pancreas: 
• 
Pancreatitis 
• 
Duodenal hemorrhage 
• 
Duodenal stricture 
• 
Duodenitis 
• 
Bleeding 
• 
Obstructive jaundice 
• 
Diarrhea 
• 
Nausea/vomiting 
• 
Epigastric/abdominal pain 
• 
Mucositis 
 
Risks associated with transduodenal placement of fiducial markers: 
 
• 
Bleeding 
• 
Pain 
• 
Pancreatitis 
• 
Infection 
• 
Nerve damage 
• 
Anesthetic related complications 
• 
Fiducial implant misplacement or migration 
• 
Foreign body reaction 
• 
Tumor seeding 
 
Specific Potential Risks associated with the study treatments 
 
Potential complications that may be associated with the use of TraceIT Tissue Spacer include, but 
are not limited to:   
 
• 
Pain associated with TraceIT Tissue Spacer injection 
• 
Pain or discomfort associated with TraceIT hydrogel 
• 
Needle penetration of pancreas during injection 
• 
Injection of TraceIT Tissue Spacer into pancreas, duodenal wall or other organs 
• 
Local inflammatory reactions 
• 
Infection 
• 
IV injection of air/material 
• 
Duodenal stricture 
• 
Duodenal mucosal damage, ulcers or necrosis 
• 
Bleeding 
• 
Delay in initiation of RT or surgery 
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• 
Potential to exacerbate local progression due to protection of undiagnosed/microscopic 
duodenal invasion 
• 
Potential for hydrogel migration 
 
The TraceIT Tissue Spacer is completely synthetic and therefore allergic reactions are not 
anticipated. 
 
8.3 
Potential Benefits to the Subject 
Potential benefits associated with the use of the TraceIT Tissue Spacer include reduced radiation 
exposure to the duodenum during the radiotherapy procedure. This has the potential to reduce 
both acute and chronic complications associated with radiation exposure to the duodenum as 
stated above as well as an improvement to the PTV coverage. 
 
8.4 
Minimization of Risks 
The risks associated with the TraceIT Tissue Spacer have been minimized by formulating the 
hydrogel with constituents that have a long history of safe use in implantable medical devices. 
The study sponsor conducted Biocompatibility testing per GLP regulation and in accordance with 
ISO 10993 – Biological Evaluation of Medical Devices.  Tests were selected and performed 
according to the type of device, intended use, and degree and duration of tissue contact.  The 
response to TraceIT Tissue Spacer Implants was evaluated in healthy tissues including 
subcutaneous and intramuscular implant locations.  All biocompatibility testing results are 
consistent with a biocompatible material. 
 
Preclinical studies were also done to evaluate the response to TraceIT Tissue Spacer adjacent to 
the duodenum and pancreas—the intended human implant site.  No adverse histologic change or 
safety concerns were noted. 
 
Based upon the results of the preclinical investigations and validated through clinical use, PEG-
based hydrogels have been shown to be safe in multiple tissue types including sensitive 
neurological and intra-abdominal tissues. The transduodenal injection procedure used for 
administration of the TraceIT hydrogel is commonly performed by endoscopists for the 
performance of pancreatic biopsies and the delivery of fiducial markers. TraceIT hydrogel is FDA 
cleared and has been used commercially for marking purposes in multiple organs including the 
esophagus20, bladder21 and cervix22. Studies evaluating application of TraceIT in these organs 
reported that the hydrogel remained dimensionally stable throughout the RT course, without 
migrating through the tissue. These organs, admittedly, have many different properties than the 
interface between the pancreas and duodenum, but TraceIT hydrogel has so far been stable, even 
in highly mobile organs such as the bladder and esophagus. 
 
Appropriate therapeutic intervention following standard medical practices will be used in the event of 
medical complications. This study will be monitored to ensure the identification, documentation and 
analysis of all adverse events, compliance with the protocol, the terms of the participating IRB to 
protect the safety and rights of all subjects, and applicable local regulations.  In addition, risks will be 
minimized through selection of investigators who are Endoscopists and Radiation Oncologists skilled 
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in the performance of periduodenal injections and/or radiation therapy and via ongoing review of both 
safety and performance data by a Clinical Events Committee. 
 
9 
ADVERSE EVENTS 
9.1 
Definitions 
Adverse Event (AE): Any untoward medical occurrence in a subject that is of new onset or has 
become worse including consequences of medical therapy resulting from a potential study-related 
delay in radiation treatment  
Adverse events are to be recorded from initiation of fiducial marker placement through the 18 
month visit.  
  
Adverse Device Effect (ADE): An adverse event that is believed to have been caused by or is 
associated with the device. 
 
Serious Adverse Event (SAE): An adverse event that: 
a. Led to death 
b. Resulted in a life-threatening illness or injury 
c. Resulted in a permanent impairment of a body structure or a body function 
d. Resulted in in-patient hospitalization or prolongation of existing hospitalization 
e. Resulted in medical or surgical intervention to prevent permanent impairment to body 
structure or a body function 
The investigator will report serious events to the Sponsor and to his/her IRB per the institution’s 
requirements and as specified in section 8.1.1. 
 
Serious Adverse Device Effect (SADE):  A serious adverse event that is believed to have been 
caused by or is associated with the device. 
 
Unanticipated Adverse Device Effect (UADE): Any serious adverse effect on health or safety, 
or any life-threatening problem or death caused by, or associated with, a device if that effect, 
problem or death was not previously identified in nature, severity or degree of incidence in the 
Investigational Plan, or any other unanticipated serious problem associated with a device that 
relates to the rights, safety or welfare of subjects.  
Event Severity: Event severity will be graded in accordance with the guidelines provided in the 
NCI Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 (NCI, Oct. 2009). For 
those events that do not have a term identified in the CTCAE, events should be identified using 
the following criteria: 
Mild:  Event causes a low level of inconvenience or discomfort, does not interfere with 
subject’s usual activities, and is usually transient; treatment not ordinarily needed for relief 
of symptoms. 
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Moderate:  Event causes moderate level of inconvenience or discomfort, may interfere with 
subject’s usual activities; new treatment or change in treatment for symptoms may be needed.  
Severe/Serious:  Event causes severe discomfort and considerable interference with 
subject’s usual activity and requires treatment and/or hospitalization. 
 
9.1.1 Recording and Reporting of Adverse Events 
All study staff are responsible for ensuring that complete safety information has been recorded on 
the CRF and in source documents. All Adverse Events (AE) must be documented throughout the 
study.  Medical assessments must be performed during each scheduled study visit and serve as the 
primary basis for identifying AEs.  Although spontaneous or elicited medical complaints will 
likely constitute the majority of AEs, any non-scheduled visit to a healthcare provider or the 
initiation of a new medication should trigger additional questioning as to the occurrence of an 
AE.  
All adverse events, regardless of severity or relationship to investigational device, will be 
collected from the time of initiation of fiducial marker placement and through the 18-month visit.  
Subjects who experience an adverse event related to TraceIT hydrogel will be followed until the 
adverse event has resolved or until the subject has stabilized and follow-up care has been 
transferred to the subject’s primary care physician. 
Any changes in a subject’s condition noted prior to the procedure should be adequately assessed 
and included in the medical history for the subject. 
Any event precipitating an intestinal acute CTCAE score of grade 2 or more must be documented 
as an adverse event. 
 
To the extent possible, the event to be recorded and reported is the event diagnosis as opposed to 
event symptoms.  Please refer to the following examples: 
 
• 
Fever, chills, nausea and vomiting in the presence of a clinically diagnosed infection 
is to be reported as an infection only. 
• 
Pain on urination in the presence of a clinically diagnosed urinary tract infection is to 
be reported as a urinary tract infection only. 
 
Reporting Serious Adverse Events 
All serious adverse events and serious adverse device effects shall be reported to the Sponsor or 
their representative (by fax or by phone) within 24 hours of the time the investigator learns of the 
event.  A written report detailing the event and signed by the investigator shall be submitted to the 
Sponsor within 5 working days.  The investigator shall notify the reviewing IRB of all serious 
adverse events occurring in the study according to the IRB’s requirements. 
Device failures or problems not associated with adverse events will be documented separately on 
the appropriate case report form. The product should be retained for evaluation.   
Investigator reporting responsibilities are summarized in Table 4. 
 
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Table 4. Investigator Reporting 
Report  
Submit To: 
Description/Time Constraints  
Regulatory Reference 
Device Malfunction 
Augmenix, Inc. 
Notify within 24 hours (or next business 
day) 
N/A 
Serious Adverse Event 
Augmenix, Inc. 
Notify within 24 hours (or next business 
day) 
Written report within 5 working days 
N/A 
IRB 
Per IRB requirements 
N/A 
Unanticipated Adverse 
Device Effect 
Augmenix, Inc. 
Notify within 24 hours (or next business 
day) 
Written report within 5 working days 
21 CFR 812.150(a)(1) 
IRB 
Within 10 working days 
21 CFR 812.150(a)(1) 
Subject Death During 
Investigation 
Augmenix, Inc. 
Notify within 24 hours (or next business 
day) 
Written report within 5 working days 
N/A 
IRB 
Per IRB requirements 
N/A 
Subject Withdrawal 
Augmenix, Inc. 
Within 5 working days 
N/A 
IRB 
Per IRB requirements 
N/A 
Withdrawal of IRB 
Approval 
Augmenix, Inc. 
Within 5 working days 
21 CFR 812.150(a)(2) 
Annual Progress 
Report* 
Augmenix, Inc.  
Submitted annually 
21 CFR 812.150(a)(3) 
IRB 
 
Deviations from 
Investigational Plan** 
Augmenix, Inc.  
 Within 5 working days 
21 CFR 812.150(a)(4) 
IRB 
Informed Consent Not 
Obtained 
Augmenix, Inc. 
Within 5 working days 
21 CFR 812.150(a)(5) 
IRB 
Per IRB Requirements 
Final Study Report 
Augmenix, Inc. 
Within 3 months after completion or 
termination of the study. 
21 CFR 812.150(a)(6) 
IRB 
*Note: Continuance review provided to the IRB will fulfill the requirements for an annual report 
to the Sponsor 
**Please refer to 21 CFR 812.150(a)(4) for the conditions under which this notification applies. 
 
9.1.2 Clinical Events Committee  
The Sponsor will utilize a Clinical Events Committee (CEC) to provide ongoing review and 
adjudication of adverse events and review of emerging device performance data.  Members of the 
CEC will include physicians with a specialty in treating subjects with pancreatic cancer including 
a radiation oncologist and a gastroenterologist. The CEC will be charged with the following 
responsibilities: 
• 
Continuous review and validation of all adverse events that occur over the course of the study 
and the subsequent classification of these adverse events as related to the device, procedure, 
radiotherapy or other. 
• 
Provide oversight for issues affecting general subject welfare, including recommendations on 
changes to the protocol or device and if appropriate recommendation concerning early study 
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termination if new information is learned that would affect the risk/benefit analysis presented 
within this clinical investigational plan. 
The Sponsor will meet with the CEC on a regular and ongoing basis.  All serious and/or 
unanticipated adverse effects will be reviewed with the CEC within 48 hours of Sponsor 
receiving such notification. 
 
9.2 
Device Malfunctions 
All device malfunctions of TraceIT Tissue Spacer will be documented on the appropriate CRF. 
The investigational device will be retained and the malfunction reported to Augmenix within 24 
hours.  Augmenix will advise whether the investigational device(s) should be returned to the 
Sponsor for analysis according to the instructions provided in the study materials.  The incidence 
of device malfunctions will be included in the final analysis. 
 
10 GENERAL INFORMATION 
10.1 Termination of Study 
Augmenix, Inc., reserves the right to discontinue the study at any stage, with suitable written notice 
to the Investigators and regulatory authorities as appropriate.  Similarly, Investigators may 
withdraw from the study subject to providing written notification to Augmenix, Inc., within 30 
days of their intent to withdraw.  However, Augmenix, Inc., and Investigators will be bound by 
their obligation to complete the follow-up of subjects already enrolled into the trial.  The subjects 
must be followed according to the clinical protocol and information obtained during subject 
follow-up shall be reported to Augmenix, Inc., on follow-up CRFs. 
Any serious and/or unexpected adverse device effects will be investigated immediately and if the 
Sponsor determines that unreasonable risk to subjects is possible, the study will be terminated, 
and all regulating authorities and participating Investigators will be notified.   
 
10.2 Monitoring Procedures 
The Investigator and the investigating center will permit authorized clinical research personnel, 
auditors and clinical monitors from Augmenix, Inc. and/or designee(s) employed by Augmenix, 
Inc., the IRB and regulatory agencies to review subject medical records, source documents, 
completed CRFs, IRB decisions, and Investigator and clinical site records at regular intervals 
throughout the study.  Subject charts and clinical records will be requested and reviewed so that 
protocol adherence and source documentation can be verified.  In instances where data protection 
regulations and/or hospital policies prohibit the direct examination of hospital records by the 
study Sponsor or designee(s), the Investigator will cooperate in a system of source data 
verification with the Sponsor. 
The monitor (or designate) will conduct pre-investigational and interim visits to all investigative 
sites and will ensure that the study protocol is thoroughly understood by all Investigators and 
appropriate supporting staff.  If the monitor discovers that an Investigator is not complying with 
the signed Investigator Agreement, the investigational plan, applicable GCP requirements, or any 
conditions of approval imposed by the reviewing IRB or regulatory authorities, the monitor will 
report to the Sponsor and take such steps necessary to promptly secure compliance.  If 
compliance cannot be secured, device shipments to the Investigator may be discontinued and the 
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Investigator’s participation in the investigation terminated.  The monitor (or designate) shall also 
require such an Investigator to return to Sponsor any unused devices. 
 
10.3 Modifications to the Protocol 
If any significant changes to the protocol are made during the course of the study, the Sponsor 
will do so in the form of a protocol amendment which must be approved by the FDA and the IRB 
prior to implementation of the changes by the Investigator. A significant change is one that 
affects the safety of the subjects, the scope of the investigation, or the scientific quality of the 
study. Changes to the protocol that do not affect the safety of the subjects, the scope of the 
investigation, or the scientific quality of the study will also be made by the Sponsor in the form of 
a protocol amendment. Implementation of these changes cannot be made until the amendment is 
reviewed and approved by the IRB. 
 
10.4 Protocol Violations / Deviations 
The Investigator will not deviate from the protocol.  In the event of an emergency, the 
Investigator shall implement any medical procedures deemed appropriate.  However, all 
such procedures must have written documentation and be promptly reported to the Sponsor 
and IRB (as appropriate). 
 
10.5 Financial Disclosure 
In accordance with 21 CFR Part 54 and 21 CFR Part 812.110(d), before the start of the 
study, the Investigator will disclose to the Sponsor any proprietary or financial interests 
he/she might hold in the investigational product or the Sponsor companies as outlined in 
the financial disclosure form provided by the Sponsor. The Investigator must update this 
information in case of significant changes during the study or within 1 year of its 
completion.  
Similar information will be provided by each co-investigator to whom the Investigator 
delegates significant study related responsibilities. 
 
10.6 Record Retention 
The Investigator will maintain the records of the investigation including all correspondence, the 
study protocol with any/all amendments, all correspondence with and approval from the IRB, the 
budget agreement, the Investigator agreement, investigational device accountability records, 
individual subject records, and signed informed consent forms in the Investigator Binder.  These 
Documents should be retained until at least 2 years after the last approval of a marketing 
application and until there are no pending or contemplated marketing applications or at least 2 
years have elapsed since the formal discontinuation of clinical development of the investigational 
product. These documents should be retained for a longer period, however, if required by the 
applicable regulatory requirements.  
 
The files may be discarded only upon notification from Augmenix, Inc.  To avoid error, the 
Investigator should contact Augmenix, Inc. before the destruction of any records and reports 
pertaining to the study to ensure they no longer need to be retained. In addition, in accordance 
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with the Investigator Agreement, Augmenix, Inc. should be contacted if the site’s Investigator 
plans to leave the Investigational Site so that appropriate arrangements can be made to replace 
him/her. 
 
 
 
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11 REFERENCES 
1. Verma V, Lazenby AJ, Zheng D, Bhirud AR, Ly QP, Are C, Sasson AR, Lin C. 
Dosimetric parameters correlate with duodenal histopathologic damage after 
stereotactic body radiotherapy for pancreatic cancer: Secondary analysis of a 
prospective clinical trial. Radiother Oncol. 2017;122:464-469 
2. Pancreatic Cancer Action Network, Pancreatic Cancer Facts 2016 accessed at 
https://www.pancan.org/wp-content/uploads/2016/02/2016-GAA-PC-Facts.pdf 
June 7, 2017 
3. Elhammali A, Patel M, Weinberg B, Verma V, Liu J, Olsen JR and Gray HA. 
Late gastrointestinal tissue effects after hypofractionated radiation therapy of the 
pancreas. Radiation Oncology; 2015;10:186 
4. Geertjan Van Tienhoven, Eva Versteijne, Mustafa Suker, Karin B.C. Groothuis, 
Olivier R. Busch, Bert A. Bonsing, Ignace H.J.T. de Hingh, Sebastiaan Festen, 
Gijs A. Patijn, Judith de Vos-Geelen, Aeilko H. Zwinderman, Cornelis J. A. Punt, 
Casper H.J. van Eijck, and all other investigators of the institutions participating 
in the trial on behalf of the Dutch Pancreatic Cancer Group J Clin Oncol 36, 2018 
(suppl; abstr LBA4002) 
5. Wolfgang CL, Herman JM, Laheru DA, Klein AP, Erdek MA, Fishman EK, 
Hruban RH Recent progress in pancreatic cancer. CA Cancer J Clin. 2013 
Sep;63(5):318-48 
6. Lim K, Chung E. Khan A, Cao D. Linehan D, Ben-Josef E., Wang-Gillam A. 
Neoadjuvant therapy of pancreatic cancer: The emerging paradigm. The 
Oncologist; 2012;17:192-200 
7. Chuong MD, Springett GM, Freilich JM et al. Stereotactic body radiation therapy 
for locally advanced and borderline resectable pancreatic cancer is effective and 
well tolerated. Int J Radiat Oncol Biol Phys 2013;86:516-522. 
8. Boone BA, Steve J, Krasinskas AM, et al. Outcomes with FOLFIRINOX for 
Borderline Resectable and Locally Unresectable Pancreatic Cancer. Journal of 
surgical oncology. 2013;108:10. 
9. NCCN guidelines version 1.2017—Pancreatic adenocarcinoma. 
https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf  Accessed 
on 3/12/1 
10. Chauffert B, Mornex F, Bonnetain F, et al. Phase III trial comparing intensive 
induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) 
followed by maintenance gemcitabine with gemcitabine alone for locally 
advanced unresectable pancreatic cancer. Definitive results of the 2000-01 
FFCD/SFRO study. Ann Oncol 2008;19:1592-1599 
11. Huguet F, Andre T, Hammel P, et al. Impact of chemoradiotherapy after disease 
control with chemotherapy in locally advanced pancreatic adenocarcinoma in 
GERCOR phase II and III studies. J Clin Oncol 2007;25:326-331. 
12. Loehrer PJ, Sr., Feng Y, Cardenes H, et al. Gemcitabine alone versus gemcitabine 
plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern 
Cooperative Oncology Group trial. J Clin Oncol 2011;29:4105-4112. 
13. Hammel P HF,  van Laethem JL, et al. Effect of chemoradiotherapy vs 
chemotherapy on survival in patients with locally advanced pancreatic cancer 
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controlled after 4 months of gemcitabine with or without erlotinib: the LAP07 
randomized clinical trial. JAMA 2016;315:1844-1853. 
14. Hazard L. The Role of Radiation Therapy in Pancreas Cancer. Gastrointestinal 
Cancer Research : GCR. 2009;3(1):20-28. 
15. Iacobuzio-Donahue CA, Fu B, Yachida S, et al. DPC4 gene status of the primary 
carcinoma correlates with patterns of failure in patients with pancreatic cancer. J 
Clin Oncol 2009;27:1806-1813 
16. Goldsmith C, Price P, Cross T et al. Dose-volume histogram analysis of 
stereotactic body radiotherapy treatment of pancreatic cancer: A focus on 
duodenal dose constraints. Semin Radiat Oncol 2016;26:149-156 
17. Murphy JD, Christman-Skieller C, Kim J, Dieterich S, Chang DT, Koong AC. A 
dosimetric model of duodenal toxicity after stereotactic body radiotherapy for 
pancreatic cancer. Int J Radiat Oncol Biol Phys. 2010;78:1420-6. 
18. Mariados N. Sylvester J, Shah D et al. Hydrogel Spacer Prospective Multicenter 
Randomized Controlled Pivotal Trial: Dosimetric and Clinical Effects of 
Perirectal Spacer Application in Men Undergoing Prostate Image Guided 
Intensity Modulated Radiation Therapy. Int J Radiation Oncol Biol Phys, 
2015;92:971-977. 
19. Ellis RJ, Mariados NF, Sylvester J. Prospective, Randomized, Patient-Blinded, 
Multicenter Trial of Perirectal Spacer in Men Undergoing Prostate IG-IMRT: 
Dosimetry and Toxicity Evaluation. Int J Radiation Oncol Biol Phys, 
2015;93:E192-D193 
20. Jin P, Hulshof MC, De Jong R, et al. Quantification of respiration induced 
esophageal tumor motion using fiducial markers and four-dimensional computed 
tomography. Radiother Oncol 2016;118: 492-497. 
21. Chao M, Ho H, Liodakis P, et al. The use of TraceIT as a fiducial marker in 
bladder radiotherapy. Int J Urol 2016;23:47. 
22. Bair RJ, Bair E, Viswanathan AN. Radiopaque polymer hydrogel used as a 
fiducial marker in gynecologic brachytherapy. Brachytherapy 2014;13:S73. 
23. Rao AD, Feng Z, Shin EJ et. al., A novel absorbable radiopaque hydrogel spacer 
to separate the head of the pancreas and duodenum in radiation therapy for 
pancreatic cancer. Int J Radiat Oncol Biol Phys 2017; 99: 1111-1120. 
24. Rao AD, Shin EJ, Beck SE et. al., Demonstration of Safety and Feasibility of 
Hydrogel Marking of the Pancreas-Duodenum Interface for Image Guided 
Radiation Therapy (IGRT) in a Porcine Model: Implications in IGRT 
for Pancreatic Cancer Patients. Int J Radiat Oncol Biol Phys. 2018; 101: 640-645. 
 
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12 APPENDICES 
12.1 APPENDIX A – AJCC PANCREAS CANCER STAGING AND ZUBROD 
PERFORMANCE SCORE SCALE 
 
AJCC PANCREAS CANCER STAGING* 
 
Primary Tumor (T) 
Tx 
primary tumor cannot be assessed 
T0 
no evidence of primary tumor 
Tis 
carcinoma in situ1** 
T1 
tumor limited to the pancreas, 2cm or less in greatest dimension 
T2  
tumor limited to the pancreas, more than 2cm in greatest dimension 
T3 
tumor extends beyond the pancreas but without involvement of the celiac axis or the 
superior mesenteric artery 
T4 
tumor involves the celiac axis or the superior mesenteric artery (unresectable primary 
tumor) 
 
Regional Lymph Nodes (N) 
NX 
regional lymph nodes cannot be assessed 
N0 
no regional lymph node metastasis 
N1 
regional lymph node metastasis 
 
Distant Metastasis (M) 
M0 
no distant metastasis 
M1 
distant metastasis 
 
Anatomic Stage/Prognostic Groups 
Stage 0 
Tis 
N0 
M0 
Stage IA 
T1 
N0 
M0 
Stage IB 
T2 
N0 
M0 
Stage IIA 
T3 
N0 
M0 
Stage IIB 
T1 
N1 
M0 
T2 
N1 
M0 
T3 
N1 
M0 
Stage III 
T4 
Any N 
M0 
Stage IV 
Any T 
Any N 
M1 
 
Notes 
*Endocrine AND exocrine tumors are now staged by a single pancreatic staging system 
**Also includes the “PanInIII” Classification 
 
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ZUBROD PERFORMANCE SCORE 
 
 
Score 
Criteria 
0 
Fully active, able to carry on all pre-disease performance without 
restriction 
1 
Restricted in physically strenuous activity but ambulatory and able 
to carry out work of a light or sedentary nature, e.g. light house 
work, office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any 
work activities. Up and about more than 50% of waking hours 
3 
Capable of only limited selfcare, confined to bed or chair more than 
50% of waking hours 
4 
Completely disabled. Cannot carry on any selfcare. Totally 
confined to bed or chair 
5 
Dead 
 
 
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APPENDIX B – COMMON TERMINOLOGY CRITERIA FOR ADVERSE 
EVENTS (CTCAE) 
 
 
 
 
 
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APPENDIX C. SAMPLE INFORMED CONSENT FORM  
 
NOTE:  This is a SAMPLE consent form provided at study start.  Subsequent updates may 
be made to the study template.   
 
AN AGREEMENT TO BE IN A RESEARCH STUDY 
 
INFORMED CONSENT DOCUMENT 
 
This consent form may contain words that you do not understand. Ask the study doctor or 
study staff to explain any words that you do not clearly understand. 
 
 
Sponsor: 
                                     Augmenix, Inc. 
City, State and Country:                    Bedford, MA, USA 
 
Protocol Number and Title:              AGX-17-001-US 
 
Study Doctor:                                     <<Investigator>> 
 
Address of Study Site(s):                   <<Study_Site>> 
                                                               <<Address>> 
                                                            <<City_State_Zip>> 
 
Telephone number:                          <<XXX-XXX-XXXX>> 
 
 
Introduction 
 
You are being asked to be part of a medical research study.  Before you decide to join, you should 
read this document.  This is called an informed consent document; it explains what will happen 
during the study.  Please ask as many questions as needed so that you can decide whether you 
want to be in the study.   
 
You have the right to know what will happen during this study, as well as the possible side 
effects and benefits of this study.  This document has important information to help you 
decide if you want to be a part of this study.  Signing the last page of this document will 
mean that you agree to participate. 
 
During the study, you will be told of any important new findings about the study device. You can 
use this information to decide about continuing in the study. 
 
Summary 
 
To summarize, consent is being sought for your participation in an early feasibility study. An 
early feasibility study is a research study of an innovative use of a medical device in a small 
number of patients to gain initial insights to the basic safety and device functionality.  
Participation in an early feasibility study means that you will be one of the first patients to receive 
treatment with the TraceIT Tissue Spacer, the device being evaluated in this research. 
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Specifically, the purpose of this research is to evaluate the feasibility and safety of an 
experimental device called the TraceIT Tissue Spacer. The TraceIT Tissue Spacer is an 
absorbable implant that will be injected between a portion of your small intestine (called the 
duodenum) and your pancreas to create space between the two organs. The expected duration of 
this study is 22 months beginning with screening and continuing until the last follow up 
visit.  The procedures to be performed are traditional fiducial marker placement and the 
experimental TraceIT injection.  Radiation therapy will take place with follow up visits at a few 
different time points.  The reasonably foreseeable risks or discomforts include risks associated 
with radiation therapy of the pancreas, the transduodenal placement of fiducial markers and the 
TraceIT material, and the risks associated with the experimental TraceIT device. There may be 
unforeseeable risks associated with participation in an early feasibility study due to limitations in 
available data and experience with the device. Possible benefits are that this research may help to 
improve radiation coverage of pancreatic tumors.  Appropriate courses of treatment may include 
standard radiation therapy without any type of spacer device.  Further discussion on each of these 
discussion points can be found in the appropriate sections of the informed consent document.   
 
 
Purpose of the study 
 
It has been explained to you that you have pancreatic cancer and you have chosen to undergo 
Radiation Therapy (RT) with fiducial markers, a common therapy used to treat people with 
pancreatic cancer.  Radiation therapy targets high-energy rays or particles in order to kill the 
cancer cells. RT is a type of radiation therapy where an x-ray of your pancreas is taken in the 
treatment room just before radiation. The fiducial markers, tiny gold seeds placed within the 
pancreas, show up on this x-ray and will help your doctor see your pancreas before delivering 
radiation. This is important because your pancreas can move every day. This x-ray will be used to 
more accurately target the cancer at each treatment.  
 
Before your first RT treatment, a radiation oncologist will create a treatment plan that will focus 
the radiation on your pancreas and minimize the amount of radiation that will hit healthy organs 
in the area around the pancreas. You will receive radiation therapy as per the institutional 
standard that will explained to you by your doctor. During this time, organs that are close to the 
pancreas, such as the duodenum, will be exposed to some radiation. Radiation exposure to the 
duodenum can cause symptoms such as duodenal bleeding, duodenal stricture, duodenitis, 
bleeding, obstructive jaundice, and diarrhea. One possible way to reduce the amount of radiation 
to the duodenum is to place a “spacer” between the pancreas and the duodenum. Placement of the 
spacer may reduce duodenal problems by moving the duodenum away from the radiation target 
site (the pancreas) during your radiation treatment.  
 
The purpose of this research is to evaluate the feasibility and safety of an experimental device 
called the TraceIT Tissue Spacer. The TraceIT Tissue Spacer was developed to provide a space 
between the pancreas and the duodenum during radiation therapy.  The TraceIT Tissue Spacer is 
a soft, gel-like material that is made mostly of water. The gel also contains iodine so your doctor 
can see it on an x-ray. The gel is injected into the space between the pancreas and duodenum 
using an endoscopic needle. The gel will be naturally absorbed by the body in approximately 7 
months. This study will evaluate whether the space created by the TraceIT Tissue Spacer can help 
improve the treatment of your pancreatic tumor. The material that the TraceIT Tissue Spacer gel 
is made from has been used in other medical implants such as a spacer between the prostate and 
rectum for radiation therapy. 
  
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What will happen during the study 
 
If you choose to participate in this study, the Study Doctor will gather information about you to 
decide if you meet the requirements of the study.  This is called “screening.” 
 
Screening does not guarantee entry into the study.  Entry into the study will depend upon the 
results of your tests, study guidelines, and the opinion of the Study Doctor.  Even if you pass the 
screening tests, there is a chance that you will not be invited to participate.  There may be other 
reasons why you cannot participate in the study. The Study Doctor and/or the study staff will 
discuss this with you. 
 
During the screening process for this study you will: 
 
• 
Provide a complete medical/surgical history 
• 
Undergo a physical exam and have your blood pressure, pulse, and temperature taken 
• 
Be asked if you are taking any medications to thin your blood 
• 
Be asked about your gastrointestinal symptoms 
• 
Have about 1-2 tablespoons of blood collected for laboratory testing 
• 
Have a sample of urine collected for analysis 
• 
Have a radiation treatment planning session. Prior to this planning session you will 
undergo a CT scan. This scan takes about one hour 
• 
Complete the EORTC-QLQ-C30 and QLQ-PAN26 quality of life questionnaires. These 
questionnaires ask you to record your opinion about how you are feeling 
 
It is very important that you provide a complete and honest medical history. Giving false, 
incomplete, or misleading information about your medical history could have serious health 
consequences. 
 
Procedure 
 
Prior to this procedure, your doctor will give you medicine to put you to sleep. Your doctor will 
discuss this medication plan with you. A sponsor representative or designee may attend your 
procedure.  
 
Screening for this study will be performed approximately 45 days prior to the injection of 
TraceIT.  During the screening visit your medical and prior surgical history will be obtained, a 
physical exam will be performed and you will be asked about your disease symptoms.  
Approximately 1 tablespoon of blood will be collected for laboratory testing. 
 
A control radiation treatment planning session will be done before the TraceIT injection.  The 
planning session involves a CT scan that may take about one hour.      
 
Experimental TraceIT Tissue Spacer Injection Procedure 
 
The spacer will be injected between the pancreas and the duodenum using a transduodenal 
approach.  Under endoscopic ultrasound guidance (EUS), a 19 or 22G fine needle will be guided 
through the EUS scope into the potential space between the duodenum and the pancreas.  Once 
the needle has been confirmed to be in the proper position and fiducial markers have been placed, 
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the TraceIT hydrogel will be injected.  Following the injection, the needle will be removed, EUS 
images will be acquired and measurements will be obtained. 
   
As part of your standard radiation treatment, a second treatment planning session will be done 
less than 28 days after the TraceIT has been injected.  This planning session will be used to get 
images of your pancreas and duodenum to help plan the radiation fields and to measure the 
distance between the pancreas and duodenum.  The planning session involves a CT and will take 
about one hour.   
 
If the TraceIT Tissue Spacer cannot be injected, a second planning simulation scan will not be 
done.  You will be asked to return for a follow-up clinic visit approximately 30 days after the 
procedure.  A physical assessment will be performed to measure your blood pressure and 
temperature and a Study Doctor will ask you about how you feel.   
 
Once the TraceIT Tissue Spacer is placed, it cannot be removed but it will be resorbed in 
approximately 7 months. 
 
RT Therapy 
 
Within 4 weeks of the procedure, your planned radiation therapy will start. You will receive 
radiation treatment for about 2 – 6 weeks. During this period, you will receive radiation 
treatments based on a schedule given to you by your doctor. While you are receiving radiation 
treatment, your doctor may ask you questions about how you are feeling and any duodenal 
symptoms you may be having.  
 
You should know that the radiation treatment course you receive in this study is not experimental 
as it would be the same even if you were not participating in this study.  
 
 
Study Visits After RT Therapy 
 
After completion of radiation therapy, you will be asked to return for five follow-up visits. The 
timing of these visits is 2-6 weeks following your radiation therapy, then 3, 6, 12, and 18 months 
from the date of your initial procedure.  
 
Consistent with standard medical practice, at the 2-6 week follow-up visit a physical assessment 
will be performed to measure your blood pressure, pulse and temperature. You will be asked 
about how you are feeling and any duodenal symptoms you may be having. You will be asked if 
you are taking any medications to treat pain or duodenal symptoms. In addition, you will have a 
CT scan so you can be evaluated for the potential to undergo a surgical procedure called the 
“Whipple” procedure, a common procedure used to remove tumors in the pancreas. In a standard 
Whipple procedure, the surgeon removes the head of the pancreas, the gallbladder and part of the 
duodenum. If you are eligible for this surgery, the study doctor will provide you with more 
information concerning the procedure.  
 
At each follow-up visit a physical assessment will be performed to measure your blood pressure, 
pulse, and temperature. You will be asked about how you are feeling and any duodenal symptoms 
you may be having. You will be asked if you are taking any medications to treat pain or duodenal 
symptoms. You will also be asked if you are taking any medications to thin your blood. The 
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EORTC-QLQ-C30 and QLQ-PAN26 questionnaires will be given to you to complete. At the 6 
month visit you will have an MRI.  
 
 
Length of the study and number of volunteers expected to participate 
 
About 6 people will be in this study at up to 4 clinics in the United States. All 6 people will be 
treated with the TraceIT gel. You will be in this study approximately 1 year and 10 months 
beginning with your screening and continuing until your last study visit. There is a possibility that 
you may be asked to return for additional follow up.  
 
Side effects and other risks 
 
One of the reasons for this study is to learn more about the possible side effects of TraceIT Tissue 
Spacer. It is important you keep the study staff informed about any possible side effects you may 
be experiencing. 
The following risks are associated with radiation therapy of the pancreas: 
• 
Pancreatitis (inflammation of the pancreas) 
• 
Duodenal bleeding 
• 
Duodenal stricture (narrowing of the duodenum) 
• 
Duodenitis (inflammation of the duodenum) 
• 
Bleeding 
• 
Obstructive jaundice (blockage of bile to the intestines) 
• 
Diarrhea 
• 
Nausea/vomiting 
• 
Abdominal pain 
• 
Mucositis (inflammation of the lining of the digestive tract) 
 
The following risks are associated with transduodenal placement of fiducial markers: 
 
• 
Bleeding 
• 
Pain 
• 
Pancreatitis 
• 
Infection 
• 
Nerve damage 
• 
Anesthetic related complications 
• 
Fiducial implant misplacement or migration 
• 
Foreign body reaction 
• 
Tumor seeding; e.g., tumor cells are transferred to other tissues near the fiducial marker  
insertion site. 
 
If you are treated with the TraceIT gel these are your additional risks, however, since this study 
represents the first use of the TraceIT gel in patients for tissue spacing there is no information to 
fully predict the frequency or severity of these risks: 
 
• 
Pain associated with TraceIT Tissue Spacer injection 
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• 
Pain or discomfort associated with TraceIT hydrogel 
• 
Needle penetration of pancreas during injection 
• 
Injection of TraceIT Tissue Spacer into pancreas, duodenal wall or other organs 
• 
Local inflammatory reactions 
• 
Infection 
• 
IV injection of air/material 
• 
Duodenal stricture 
• 
Damage to the tissues of the duodenum including ulcers or necrosis (tissue death) 
• 
Bleeding 
• 
Delay in initiation of RT or surgery 
• 
Potential to protect undiagnosed/microscopic duodenal cancer cells from radiation 
 
The TraceIT Tissue Spacer is completely synthetic and therefore allergic reactions are not 
anticipated. 
 
Although the above risks are possible, the TraceIT gel has been tested in studies in animals and 
was determined to be safe.  
 
Risks of Radiation Exposure: 
Participation in this research study may involve exposure to radiation from the additional research CT 
scan performed for the purposes of the study. The amount of radiation exposure that you will receive 
from the extra CT scan is about 1 rem (a unit of radiation exposure) to your abdomen, with minimum 
exposure of other areas of your body. This amount of radiation is approximately one thousand times 
less than the amount of radiation you will be receiving as part of your cancer therapy. Therefore, the 
risk associated with the additional amount of radiation exposure that you will receive from taking part 
in this study is felt to be very low.  
 
Unforeseeable risks 
 
The administration of the study device may involve risks to you that are presently unforeseen and 
unknown. Rare or unknown side effects could possibly occur, some of which could be life-
threatening. 
 
Minimizing Risk 
 
During your participation in this study you will be closely monitored for any potential 
complications so that your study doctor can provide treatment as soon as possible. If for some 
reason the TraceIT gel cannot be successfully placed between the duodenum and pancreas this 
will not affect your ability to undergo radiation therapy.  
 
The risks to an embryo, fetus and breastfeeding baby are not known at this time.  
 
Possible benefits of the study 
 
Taking part in this study may or may not provide any help to you since the actual benefits of the 
TraceIT Tissue Spacer are not known.  A possible benefit of the TraceIT Tissue Spacer is that it 
may help to improve the radiation coverage of your tumor.  Future patients with pancreatic cancer 
may also benefit from the information obtained during this study. 
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Compensation 
 
There will be no additional cost to you because you are participating in the study. Tests that are 
not part of your standard medical care, but are required as part of your participation in this study 
(for example, the extra MRI and CT scan), will be paid for by the study sponsor.  
 
Alternatives to participating 
 
There are other treatments available if you decide not to be in the study.  Treatments may include 
standard external beam radiation therapy (EBRT) therapy without any type of spacer device.  The 
Study Doctor can discuss these options and decide what treatment is best for you. 
 
Confidentiality 
 
If you participate in this study, the Sponsor and their delegates will look at and copy your study 
medical records.  In addition, study medical records will be given to the Sponsor, the Institutional 
Review Board (IRB), the U.S. Food and Drug Administration, and other regulatory agencies.  If 
study results are published, your name will not be used.  Any information regarding your 
participation in this study that identifies you by name will not be released to any other party 
without your written consent.  It is likely that the results of this study will be published in one or 
more medical journals or presented at medical meetings.  Any such publication will not identify 
you by name. 
 
Photo/Video Release 
 
You give the Sponsor the right to use, copy, and give out the video or pictures from the video 
taken of your ultrasound.  We will make every effort to hide your identity.   
 
Your pictures/videos will only be used for training, advertising or in scientific conferences, 
journals or magazines.  Your pictures/videos may also be edited or used as part of a larger 
presentation, along with other pictures or videotapes.  The Sponsor may give other people or 
companies permission to use your pictures/videos. 
 
In case of an injury related to this research study 
 
Treatment will be offered if you have an injury or problem as a result of being in this study. If 
you have any problems directly from the use of the TraceIT Tissue Spacer, Augmenix, Inc. will 
pay for the reasonable costs of medical treatment that are not covered by your health insurance or 
other provider.  No other forms of payments are available.   
 
If you have any payment or medical questions or if you think you have had a study related injury, 
you may contact Doctor ____________________ at ___________________.   
 
Legal Rights 
 
You do not lose any legal rights by signing this consent document.  The above statement, “In Case 
of an Injury Related to This Research Study,” does not stop you from getting legal help in case of 
negligence. 
 
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CONFIDENTIAL 
 
 
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Whom to contact 
 
You may contact the Study Doctor at ___________________: 
 
• 
for answers to questions about this research study 
 
• 
to report a research related injury or 
 
• 
for information about study procedures 
 
If you are unsuccessful in your attempt to contact the Study Doctor or study staff, please contact 
the local IRB at _______________________.  Please do so directly and immediately by calling 
_________________. 
 
You may contact ________________________________________ if you would like to speak 
with someone unrelated to the research and/or have "questions, concerns, or complaints" 
regarding the research study. 
 
The IRB has approved this study and this consent document.  An IRB is a group of scientific and 
non-scientific people who review and approve or reject research.  This group is also required by 
regulatory authorities to do periodic review of ongoing research studies.  Questions about your 
rights as a participant may be addressed to: 
 
 
[Hospital contact and phone number] 
 
Leaving the study 
 
Your decision to be in this study is up to you.  You have the right to leave this study at any time. If 
you do not want to be in the study, there will be no penalty to you, and you won’t lose any benefits 
that you are entitled to. 
 
However, if you wish to leave this study, please call the Study Doctor or study staff right away at 
the telephone number listed on page one of this informed consent document to schedule study exit 
procedures. 
 
Your part in this study may be stopped at any time without you being asked.  The following people 
can stop your participation: 
 
• 
the Study Doctor 
 
• 
the IRB 
 
• 
The United States Food and Drug Administration (FDA) 
 
• 
the Sponsor 
 
If you do not follow the study procedures, you may be taken out of the study. 
 
Authorization to use and disclose health information (HIPAA) 
 
Your personal health information is protected by the Health Insurance Portability and 
Accountability Act of 1996 (HIPAA). During your participation in this research study, the Study 
Doctor and study staff will collect and create personal health information about you and record it on 
forms. This section provides information about how these medical records and health information 
will be used and disclosed in this clinical research study. If you volunteer to take part in this 
research study, you have the right to know that others may know your identity. Study information 
may identify you in the following ways: 
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• 
Name 
• 
Other details about you 
 
This study includes a number of businesses and government agencies. They may use your health 
information and share it with others. We want you to know who may use this information and 
how they may use it.  
 
We also want to tell you about your rights before you agree to take part in the study. 
 
Who may use and give out information about you? 
 
The Study Doctor and study staff will have information about your health that tells your identity. 
They may give this information to others during and after the study. 
 
Who may see this information? 
 
The study sponsor also may see your health information and know your identity. “Sponsor” 
includes any people or companies working for or with the sponsor or owned by the sponsor. They 
all have the right to see information about you during the study. 
 
The following people, agencies, or businesses may get information that identifies who you are: 
• 
The Sponsor and its representatives 
• 
Doctors and healthcare professionals taking part in this study 
• 
U.S. Food and Drug Administration (FDA) 
• 
U.S. Department of Health and Human Services (DHHS) 
• 
Government agencies in other countries 
• 
Government agencies that must receive reports about certain diseases 
• 
The Institutional Review Board (IRB) 
 
What information may be used and shared? 
 
If you decide to be in this study, medical information that identifies you and relates to your 
information will be created. This may include the following types of medical information: 
 
• 
Information obtained from the procedures used to find out whether you are eligible to take 
part in this study. This may include information that you may release to us, including 
information about your health history. 
• 
All information about you which is collected or created during the study for research 
purposes. It also includes your personal health information that is related to this study and 
that is maintained in your medical records at this institution and at other places such as other 
hospitals and clinics where you may have received medical care. Examples of your personal 
health information include your health history, how you respond to study activities or 
procedures, laboratory and other test results, medical images, and information from study 
visits, phone calls, questionnaires, and physical examinations. 
 
Why will this information be used and/or shared? 
 
Information about you and your health, that might identify you, may be given to others to carry 
out the research study. The sponsor will analyze and evaluate the results of the study. In addition, 
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CONFIDENTIAL 
 
 
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people from the sponsor and its consultants will be visiting the research site. They will follow 
how the study is done, and they will be reviewing your information for this purpose. 
 
The information may be given to the FDA. It may also be given to governmental agencies in 
other countries. The information may also be used to meet the reporting requirements of 
governmental agencies.  
 
The results of this research may be published in scientific journals or presented at medical 
meetings, but your identity will not be disclosed. 
 
The information may be reviewed by the Institutional Review Board. 
 
What if you decide not to give permission to use and give out your health information? 
 
By signing this informed consent document, you are giving permission to use and give out the 
health information listed above for the purposes described above. If you refuse to give 
permission, you will not be able to be in the research study. 
 
May you review or copy the information obtained from you or created about you? 
 
You have the right to review and copy your health information. However, if you decide to be in 
this study and sign the consent document, you will not be allowed to look at or copy your 
information until after the research is completed.  
 
May you withdraw or revoke (cancel) your permission? 
 
This permission does not stop automatically.  
 
You may withdraw or take away your permission to use and disclose your health information at 
any time. You do this by sending written notice to the Study Doctor. If you withdraw your 
permission, you will not be able to continue being in this study. 
 
When you withdraw your permission, no new health information that might identify you will be 
gathered after that date. Information that has already been gathered may still be used and given to 
others. This would be done if it were necessary for the research to be reliable. 
 
Is your health information protected after it has been given to others? 
 
If you give permission to give your identifiable health information to a person or business, the 
information may no longer be protected. There is a risk that your information will be released to 
others without your permission. 
 
Informed consent statement 
 
It is important that you read and understand several general principles, which apply to all who 
take part in this study:  
• 
Your participation in the study is entirely voluntary.   
• 
Personal benefits to you may or may not result from taking part in the study, but 
knowledge may be gained from your participation that will benefit others. 
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CONFIDENTIAL 
 
 
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• 
You may withdraw from the study at any time without penalty or loss of any benefits to 
which you are otherwise entitled.   
• 
You will be told about any new information discovered during the course of this study 
that may affect your willingness to continue participating in the study.  
 
Informed consent agreement 
I understand that I am being asked to participate in a research study to evaluate the use of the 
TraceIT Tissue Spacer. After reading and understanding the information in this Informed Consent 
document, and after having received answers to any additional questions or concerns I had, I freely 
and voluntarily agree to participate in this study and to comply with the study requirements.   
 
I understand that my personal physician may be informed that I am participating in this research 
study or have stated my disagreement to such notification and agree to the use of relevant personal 
data for the purpose of this clinical study. Please indicate below whether you want us to notify your 
primary care physician or your specialist of your participation in this study. 
 
______ Yes, I want the study doctor to inform my primary care physician/specialist of my 
participation in this study.  
______ No, I do not want the study doctor to inform my primary care physician/specialist of my 
participation in this study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Participant   
 
 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Participant 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Person Explaining Consent Document 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Person Explaining Consent Document 
 
 
 
You will be given a copy of signed consent document to keep. 
 
 
 
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Augmenix, Inc. 
 
CONFIDENTIAL 
 
 
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APPENDIX D. INVESTIGATOR AGREEMENT AND CERTIFICATION 
 
 
THE TIPS PILOT STUDY 
 
 
I hereby agree to participate in the clinical investigation of the TraceIT Tissue Spacer sponsored by 
Augmenix Inc. (hereinafter “Study Sponsor”).  I agree to conduct this investigation in accordance with the 
agreement, the investigational plan, 21 CFR Part 812, other applicable FDA regulations and conditions of 
approval imposed by the reviewing IRB or FDA.  I agree to supervise all use of the investigational device 
and to ensure appropriate informed consent is obtained from all subjects prior to inclusion in this study. 
The rights, safety, and well-being of clinical investigation subjects shall be protected consistent with the 
ethical principles laid down in 21 CFR Part 50. This shall be understood, observed, and applied at every 
step of the investigation. 
 
 
I understand that this investigation will be monitored by the Study Sponsor and/or a designee employed by 
Study Sponsor.  This monitoring will involve periodic inspection of my investigational site and ongoing 
review of the data that is submitted by me to the Study Sponsor.  I am also aware that I may be inspected 
by a representative of the Food and Drug Administration (FDA) and other regulatory authorities/agencies 
to verify compliance with applicable requirements related to clinical research on human subjects.  I am 
aware that my contact for all matters related to this investigation is Augmenix at (781) 895-3235. 
 
 
I am aware that Study Sponsor reserves the right to discontinue this investigation at any time. In the event 
that I decide to discontinue my participation as an Investigator in this study, I will notify Study Sponsor 30 
days prior of my intent to discontinue.  I understand that I am obligated to complete the follow up of the 
subjects already participating in the investigation. 
 
 
Any data generated as a result of this investigation will be the exclusive property of Study Sponsor who 
retains all rights of publication.  I understand that Study Sponsor encourages me to pursue independent 
publications related to my experience with this investigational device with the understanding that Study 
Sponsor reserves the right of prior review and approval of these publications. 
 
 
I agree to provide to the Sponsor a current curriculum vitae along with the curriculum vitae of those 
physicians at this institution who will be using this investigational device or participating in this study as 
sub-Investigators under my supervision.  These CVs include the extent and type of our relevant experience 
with pertinent dates and locations.  I certify that I have not been involved in an investigation that was 
terminated for noncompliance at the insistence of Study Sponsor, this institution’s IRB, or FDA. 
 
 
I understand that this investigation, protocol, and trial results are confidential and I agree not to disclose 
any such information to any person other than a representative of Study Sponsor or a regulatory authority 
(IRB/FDA/Office of Human Research Protections-OHRP) without the prior written consent of Study 
Sponsor. 
 
I will provide financial information, as indicated in U.S. Code of Federal Regulations: 21 CFR Part 
812.43(c)(5) and 21 CFR Part 54 
 
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Augmenix, Inc. 
 
CONFIDENTIAL 
 
 
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Accepted by: 
 
___________________________________________________________________________________ 
Principal Investigator Signature                          Date             
 
Printed name 
 
 
___________________________________________________________________________________ 
Co-Investigator Signature                                    Date             
 
Printed name 
 
___________________________________________________________________________________ 
Co-Investigator Signature                                    Date             
 
Printed name 
 
 
___________________________________________________________________________________ 
Co-Investigator Signature                                    Date             
 
Printed name 
 
 
___________________________________________________________________________________ 
Co-Investigator Signature                                    Date             
 
Printed name 
 
 
___________________________________________________________________________________ 
Co-Investigator Signature                                    Date             
 
Printed name 
 
 
 
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