Initial Evaluation of Role of Early Interim 18F-FLT PET/CT for Outcome Prediction in Pancreatic Adenocarcinoma
Phase: PHASE2
Conditions: Pancreatic Adenocarcinoma
Sponsor: University of Texas Southwestern Medical Center

Official title: Initial evaluation of role of early interim 18F-FLT PET/CT for 
                      outcome prediction in pancreatic adenocarcinoma 
 
NCT number: NCT03318497 
IRB Approved date: Aug 19, 2020 

 
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PROTOCOL Version 7 
PROTOCOL TITLE 
 
Initial evaluation of role of early interim 18F-FLT PET/CT for outcome prediction in 
pancreatic adenocarcinoma 
 
Principal Investigator: 
Daniella F Pinho, MD  
 
 
 
 
UT Southwestern Medical Center 
 
 
 
 
Address: 5323 Harry Hines Blvd, Dallas, TX, 75390 
 
 
 
 
(Phone): (214) 648-8218 
 
 
 
 
(Fax): (214) 648-7785 
 
 
 
 
Email: Daniella.pinho@utsouthwestern.edu 
 
 
 
 
 
Xiankai Sun, Ph.D. 
Cyclotron and Radiochemistry Program 
UT Southwestern Medical Center 
 
 
 
 
5323 Harry Hines Blvd, Dallas, Texas 75390-8542 
 
 
 
 
(Phone): 214-645-5978 
 
 
 
 
Email: Xiankai.Sun@UTSouthwestern.edu  
Dr. Sun is a radiochemist and is not involved in patient 
care 

 
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Guiyang Hao, Ph.D. 
 
 
 
 
Cyclotron and Radiochemistry Program 
 
 
 
 
UT Southwestern Medical Center  
 
 
 
 
5323 Harry Hines Blvd, Dallas, Texas 75390-8542 
 
 
 
 
(Phone): 214-645-7619 
 
 
 
 
Email: Guiyang.Hao@UTSouthwestern.edu  
 
 
 
Dr. Hao is a radiochemist and is not involved in patient care 
 
 
Marianna Dakanali, Ph.D. 
 
Cyclotron and Radiochemistry Program 
 
 
 
 
UT Southwestern Medical Center  
 
 
 
 
5323 Harry Hines Blvd, Dallas, Texas 75390-8542 
 
 
 
 
(Phone): 214-645-7611 
 
 
 
 
Email: Marianna.Dakanali@UTSouthwestern.edu  
Dr. Dakanali is the Regulatory Affairs Officer of the 
Cyclotron and Radiochemistry Program and she is not 
involved in patient care 
 
Biostatistician: 
 
Yin Xi 
 
 
 
 
UT Southwestern Medical Center 
 
 
 
 
Address: 5323 Harry Hines Blvd. Dallas, TX 75390-9061 
 
 
 
 
(Phone): 214-648-7755 
 
 
 
 
(Fax): 214-648-7784 
 
 
 
 
Email: yin.xi@utsouthwestern.edu 
 
 
Study Drug:  
 
3’-deoxy-3’-[18F]-fluorothymidine 
 
IND Number: 
 
133348 
 
IND Holder Name:  
Neil Rofsky, MD.  
 
Funding Source:  
 
Shelby Pancreatic Cancer Research Program 
 
Version Date: 
 
June 24, 2020 
 
 
 
UT Southwestern Medical Center (UTSW) 
Harold C. Simmons Cancer Center 
Attn: Clinical Research Office 
5323 Harry Hines Blvd. MC 9179 
Dallas, Texas 75390-9179 

 
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Signature Page 
 
 
The signature below constitutes the approval of this protocol and the attachments, and provides 
the necessary assurances that this trial will be conducted according to all stipulations of the 
protocol, including all statements regarding confidentiality, and according to local legal and 
regulatory requirements and applicable U.S. federal regulations and ICH guidelines. 
 
 
 
Principal Investigator (PI) Name:_____________________________ 
 
 
 
PI Signature: _____________________________ 
 
 
 
Date:____________________ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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TABLE OF CONTENTS 
 
LIST OF ABBREVIATIONS .......................................................................................... 1 
STUDY SCHEMA ............................................................................................................ 3 
STUDY SUMMARY ......................................................................................................... 0 
1.0 BACKGROUND AND RATIONALE .......................................................................2 
1.1 Disease Background .................................................................................................... 2 
1.2 Study Agent(s) Background and Associated Known Toxicities ............................. 3 
1.3 Other Agents ................................................................................................................ 4 
1.4 Rationale ...................................................................................................................... 4 
1.5 Correlative Studies ...................................................................................................... 4 
2.0 STUDY OBJECTIVES ...............................................................................................5 
2.1 Primary Objectives ..................................................................................................... 5 
2.2 Secondary Objectives.................................................................................................. 5 
2.3 Exploratory Objectives ............................................................................................... 5 
2.4 Endpoints ..................................................................................................................... 5 
3.0 SUBJECT ELIGIBILITY ...........................................................................................6 
3.1 Inclusion Criteria ........................................................................................................ 6 
3.2 Exclusion Criteria ....................................................................................................... 7 
4.0 STUDY PLAN ..............................................................................................................7 
4.1 Study duration: ........................................................................................................... 9 

 
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5.0 STUDY PROCEDURES ............................................................................................ 9 
5.1 Screening/Baseline Procedures .................................................................................. 9 
5.2 Time and Events Table ............................................................................................. 10 
5.3 Removal of Subjects from Study ............................................................................. 10 
5.4 Safety .......................................................................................................................... 11 
6.0 Measurement of Effect ..............................................................................................12 
6.1 Antitumor Effect- Solid Tumors.............................................................................. 12 
6.2 Disease Parameters ................................................................................................... 12 
6.3 Methods for Evaluation of Measurable Disease ..................................................... 13 
6.4 Response Criteria ...................................................................................................... 13 
6.5 Safety/tolerability ...................................................................................................... 15 
7.0 ADVERSE EVENTS .................................................................................................15 
7.1 Adverse Event Monitoring ....................................................................................... 15 
Definition ......................................................................................................................... 16 
Severity............................................................................................................................. 16 
Serious Adverse Events .................................................................................................. 17 
Unanticipated Problems Involving Risks to Subjects or Others (UPIRSOs):........... 18 
Follow-up ......................................................................................................................... 18 
Reporting ......................................................................................................................... 18 
SAEs ................................................................................................................................. 19 
Unanticipated Problems Involving Risks to Subjects or Others (UPIRSOs) ............ 19 
8.0 DRUG INFORMATION ...........................................................................................20 

 
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9.0 STATISTICAL CONSIDERATIONS .....................................................................21 
9.1 Study Design/Study Endpoints ................................................................................ 21 
9.2 Sample size ................................................................................................................. 22 
9.3 Data Analyses Plans .................................................................................................. 22 
10.0 STUDY MANAGEMENT ......................................................................................22 
10.1Conflict of Interest .................................................................................................. 22 
10.2Institutional Review Board (IRB) Approval and Consent .................................. 23 
10.3Registration/Randomization Procedures .............................................................. 23 
10.4Data Management and Monitoring/Auditing ....................................................... 23 
10.5Adherence to the Protocol ...................................................................................... 24 
10.6Emergency Modifications ....................................................................................... 24 
10.7Other Protocol Deviations/Violations .................................................................... 24 
10.8Amendments to the Protocol .................................................................................. 25 
10.9Record Retention ..................................................................................................... 26 
10.10Obligations of Investigators ................................................................................. 26 
11.0 REFERENCES ........................................................................................................26 

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LIST OF ABBREVIATIONS 
AE 
Adverse Event 
ALT 
Alanine Aminotransferase 
ALC 
Absolute Lymphocyte count 
ASCO 
American Society of Clinical Oncology 
AST 
Aspartate Aminotransferase 
BUN 
Blood Urea Nitrogen 
CBC 
Complete Blood Count 
CMP 
Comprehensive Metabolic Panel 
CR 
Complete Response 
CT 
Computed Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLT 
Dose Limiting Toxicity 
DOT` 
Disease Oriented Team 
DSMC 
Data and Safety Monitoring Committee 
ECOG 
Eastern Cooperative Oncology Group 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
H&P 
History & Physical Exam 
HRPP 
Human Research Protections Program 
IHC 
Immunohistochemistry 
IND 
Investigational New Drug 
IV (or 
iv) 
Intravenously 
MRI 
Magnetic Resonance Imaging 
MTD 
Maximum Tolerated Dose 
NCI 
National Cancer Institute 

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ORR 
Overall Response Rate 
OS 
Overall Survival 
PBMCs 
Peripheral Blood Mononuclear Cells 
pCR 
Pathologic Complete Response 
PD 
Progressive Disease 
PET 
Positron Emission Tomography 
PFS 
Progression Free Survival 
p.o. 
peros/by mouth/orally 
PR 
Partial Response 
RCB 
Residual Cancer Burden 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SAE 
Serious Adverse Event 
SCCC 
Simmons Comprehensive Cancer Center 
SD 
Stable Disease 
SGOT 
Serum Glutamic Oxaloacetic Transaminase 
SGPT 
Serum Glutamic Pyruvic Transaminase 
WBC 
White Blood Cells 

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STUDY SCHEMA 
The schema should represent your study design, along with corresponding descriptive text, as 
applicable.  
 
 
Optional -18F FDG PET/CT – research study, if a clinically 
directed scan was not obtained within 30 days of 18F FLT 
18F FLT PET/CT (Baseline) – research study 
Newly diagnosed biopsy proven pancreatic adenocarcinoma 
(resectable, borderline resectable or locally advanced) (standard of 
care FDG PET/CT, CT and or MRI) 
Completion of chemotherapy (standard of care) 
2 cycles of chemotherapy (Standard of care) 
Interim therapy 18F-FLT PET/CT after 2 cycles of 
chemotherapy– research study 
Anatomic evaluation with CT or MRI – standard of care 
Clinical Follow up to 2 years – standard of care 

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STUDY SUMMARY 
Title 
Initial evaluation of role of early interim 18F-FLT 
PET/CT for outcome prediction in pancreatic 
adenocarcinoma 
 
Short Title 
FLT PET/CT and Pancreatic cancer early therapy assessment 
Protocol Number 
Version 7 
Phase 
Clinical study phase (e.g., Phase II) 
Methodology 
Prospective cohort study 
Study Duration 
2 years 
Study Center(s) 
UT Southwestern Medical Center - Single-center  
Objectives 
• To assess if percentage change in 18F-FLT PET/CT 
quantitative parameters (SUV max, or SUV peak or 
proliferative tumor volume) after 2 cycles of 
neoadjuvant chemotherapy can predict overall 
survival at 1 and 2 years and progression free survival 
at 6 months and 1 year in patients with resectable, 
borderline resectable or locally advanced pancreatic 
adenocarcinoma.  
 
Number of Subjects 
20 patients with pancreatic adenocarcinoma 

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Diagnosis and Main 
Inclusion and exclusion 
Criteria 
• Patients must be over 18 years old and capable and 
willing to provide informed consent 
• Patients of childbearing potential must have a 
negative urine or serum pregnancy test within 7 days 
prior to PET/CT imaging per institution’s standard of 
care  
• Medically stable as judged by patient’s physician 
• Patients must have an ECOG performance status of 0-
3 (restricted to ECOG PS 0-2 if age >70 years) 
• Patients with known allergic or hypersensitivity 
reactions to previously administered 
radiopharmaceuticals of similar chemical or biologic 
composition to FLT are not eligible  
• Patient must NOT be breast-feeding  
• Histologically confirmed resectable, borderline 
resectable or locally advanced pancreatic 
adenocarcinoma 
• Patient have measurable disease (by RECIST 1.1 
criteria)  
• Patients with a history of prior therapy for pancreatic 
adenocarcinoma are NOT eligible  
• Patient must not weigh more than the maximum 
weight limit for the table for the PET/CT scanner 
(>200kg or 440lbs) . 
• Patient must be able to lie still for a 20 to 30 minutes 
for whole body PET/CT scan  
Study Product(s), Dose, 
Route, Regimen 
Fluorothymidine is an analog of the nucleoside thymidine 
(deoxythymidine) but the 3’-F atom prevents FLT from 
following the full biochemical pathway of thymidine. FLT is 
transported from the blood into cells by active transport; it 
does not freely diffuse across the cell membrane. Once in the 
cell, FLT is a substrate for thymidine kinase I (TK1) and is 
phosphorylated but is not incorporated into DNA. 5mCi of 
FLT (+/- 20%) will be given intravenously. 
Duration of administration 
IV push over one to two minutes 
Reference therapy 
Not applicable 

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Statistical Methodology 
The difference in SUVmax, SUVpeak and proliferative tumor 
volume between baseline and post 2 cycles of chemotherapy 
will be correlated with overall survival at 1 and 2 years 
(primary clinical outcome endpoint) and progression free 
survival at 6 months and at 1 year (secondary clinical outcome 
endpoint) of patients with resectable, borderline resectable or 
locally advanced pancreatic adenocarcinoma using univariate 
and multiple cox regression model. Patient demographic 
information and tumor and treatment characteristics such as 
sex, race, tumor grade, cancer stage, last treatment modality, 
will also be included. P value less than 0.05 will be considered 
as statistical significant. 
Areas under the ROC curve (AUC) and corresponding 95% 
confidence interval will be calculated for all models. Leave 
one out cross validation will be applied to avoid over-fit. 
 
 
1.0 
BACKGROUND AND RATIONALE 
1.1 
Disease Background 
Pancreatic cancer is the fourth most lethal malignancy overall, with a projected death toll 
of more than 40,000 for 2016 in the US1. Pancreatic adenocarcinoma is usually locally 
advanced and / or metastatic at the time of diagnosis, preventing surgical resection in the 
majority of cases2. Initial treatment strategies for resectable, borderline resectable or 
locally advanced pancreatic adenocarcinoma includes chemotherapy and chemoradiation 
(in selected patients). The main therapeutic goal is to reduce disease burden to allow 
surgical resection, which is the only curative treatment for pancreatic adenocarcinoma to 
date. After initial treatment, response is revaluated by anatomical imaging, usually by a 
dedicated contrast enhanced CT, which is preferred, or alternatively MRI. However, 
objective evaluation of response in pancreatic cancer is often difficult. CT and MRI have 
some significant limitations, such as inability to clearly outline tumor borders due to the 
infiltrative nature of pancreatic adenocarcinomas, and post-treatment imaging changes 
that can simulate tumor. Additionally, it is an anatomic method only that relies on 
relatively slow macroscopic tumor changes without information regarding tumor 
metabolism.  
2-Deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) PET/CT, which is a marker of glucose 
metabolism, is an alternative imaging method, and multiple studies have shown an 
overall sensitivity of 73 to 94% for detection of pancreatic adenocarcinoma, while 
specificity ranges from 60 to 89%. The specificity is reduced because 18F-FDG PET/CT 
is a non-specific tracer that also accumulates in some benign conditions with increased 
glucose metabolism (such as inflammation). Moreover, the rate of false negatives is also 

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increased in this population because 20 to 30% of patients with pancreatic 
adenocarcinoma have hyperglycemia, which may significantly decrease the amount of 
FDG uptake3-13. For these reasons, more accurate novel PET tracers are expected to have 
a significant clinical impact. 
 
1.2 
Study Agent(s) Background and Associated Known Toxicities 
 
 
The pharmacology of 3’-deoxy-3’’[18F]-fluorothymidine (FLT) is based on its 
action as an inhibitor of DNA synthesis. Intracellular metabolism of FLT produces FLT-
phosphates but these nucleotides inhibit endogenous DNA polymerases because they lack 
a 3'-hydroxyl substituent. This results in premature chain termination of DNA synthesis14. 
 
In a study performed at the University of Washington, Turcotte and colleagues 
assessed the toxicity of 18F-FLT in twenty patients with proven or suspected diagnosis of 
non-small cell lung cancer15. All patients gave written informed consent to the 18F-FLT 
injection, and subsequent PET imaging and blood draws. Blood samples were collected 
for each patient at multiple times before and after 18F-FLT. These samples were assayed 
for comprehensive metabolic panel, total bilirubin, and complete blood and platelet 
counts. In addition, a standard neurological examination by a qualified physician was 
performed for each patient before and immediately after 18F-FLT. All 18F-FLT doses 
were calculated based on patient weight (2.59 MBq/kg = 0.07 mCi/kg) with a maximal 
dose of 185 MBq (5.0 mCi). Starting with the 18F-FLT injection, dynamic PET images 
were acquired for 90 or 120 minutes. By placing a region-of-interest in the center of the 
left ventricular chamber, blood time activity curves were generated for each patient from 
the dynamic PET data and then extrapolated to 720 minutes. This provided a measure of 
the area under the 18F-FLT concentration curve for 12 hours (AUC12). A separate 
estimation of the AUC12 was also obtained from sequential blood samples collected 
during PET data acquisition. No side effects were reported by patients or observed. No 
change was observed in the neurological status of patients. A neurological examination 
was performed by an experienced neurologist prior to 18F-FLT administration, the day 
after 18F-FLT administration, and at four weeks post 18F-FLT administration. Only 
albumin, red blood cell count, hemoglobin, and hematocrit show a statistically significant 
decrease over time. These changes were attributed to IV hydration during PET imaging 
and to subsequent blood loss at surgery. The AUC12 values estimated from imaging data 
are not significantly different from those found from serial measures of 18F-FLT blood 
concentrations (P = 0.66). No significant neurologic sequelae have been attributed to 18F-
FLT use in pet imaging to date. As a result, peripheral neuropathy, which had been listed 
as a possible risk based upon observations at significantly higher doses in early 
therapeutic HIV studies, is no longer considered a risk of 18F-FLT use in a micro-dose 
imaging setting. Screening for peripheral neuropathy is not justified based upon the 
available evidence in multiple 18F-FLT imaging trials. 

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In another study, 12 patients with brain tumors were enrolled16. Overall, 2 of the 
12 subjects receiving 18F-FLT experienced an elevation in BP from baseline to two hours 
post infusion: Subjects 1 (119/56 – 133/66) and 4 (120/78 – 163/74). In Subject 4, 
abnormal BP was attributed to discomfort from the head immobilization device. There 
were no clinically relevant events reported. All subjects performed consistently on the 
pre- and post- neurological exams and there were no changes in status. Four of these 
analytes demonstrated statistically significant changes on one-way ANOVA: potassium, 
carbon dioxide, total protein, and albumin. Some of the other values were above or below 
normal, but no pattern was seen except that many were lower on the day of the study. 
These decreases are attributed to two main factors. Normal saline infusion, which 
expands blood volume, and arterial blood sampling for kinetic analysis are performed 
during the procedure, both of which will cause a general lowering of the concentration of 
blood components. The subsequent recovery of these values to baseline is consistent with 
this explanation and consistent with the results obtained by Turcotte. 
 
As discussed above, the mechanism of action of FLT’s toxicity at therapeutic 
dosing levels is based on inhibition of DNA synthesis. Total exposure to the radiolabeled 
agent for PET imaging, will be several thousand times lower than the exposure at which 
toxicity has been observed in humans. Nevertheless, as with all investigational drugs, 
patients receiving 18F-FLT should be observed for adverse events, and promptly treated 
should any adverse effects occur. 
1.3 
Other Agents 
Not applicable. 
1.4 
Rationale 
The thymidine analog 3’-deoxy-3’’[18F]-fluorothymidine (FLT) is a proliferation marker, 
which has the potential to perform better in patients with pancreatic adenocarcinoma14.  
 
Interim studies (usually after 2 cycles of chemotherapy) are commonly used for 
early restaging and to better tailor further management, offering more timely evidence to 
support changing or maintaining therapies, when compared to conventional imaging 
studies. It also has an important role in prognostication. Such study strategies have been 
extensively explored for breast cancer, and at least three different studies showed 
significant correlation between findings in early 18F-FLT PET/CT and patients’ response 
to chemotherapy, giving the possibility of change in chemotherapy regimens in non-
responder patients17-19. 
 
The increased specificity of 18F-FLT PET/CT has an enormous advantage over 
18F-FDG PET/CT as an early assessment study, especially with radiation therapy. 18F-
FDG PET/CT is known to suffer from an increased rate of false positives due to non-
specific uptake in post-therapy inflammatory changes during treatment caused by 
macrophage / monocyte infiltration20. 18F-FLT PET/CT has the potential to overcome this 
imitation as a more specific tracer for tumor proliferation. 
1.5 
Correlative Studies 

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Few studies have explored the role of 18F-FLT PET/CT in pancreatic cancer. One study, 
which enrolled 31 patients undergoing resection, demonstrated a lower false-positive rate 
compared to 18F-FDG PET/CT21. A second study reported that 18F-FLT PET/CT was 
detected exclusively in malignant tumors, with a specificity of 100% for detection of 
pancreatic adenocarcinoma22. A more recent study evaluated the role of FLT PET/CT 
using a temporal-intensity information-based voxel-clustering approach termed kinetic 
spatial filtering (FLT PET/CTKSF) for early prediction of response and survival 
outcomes in locally advanced and metastatic pancreatic cancer patients receiving 
gemcitabine-based chemotherapy. The authors found that FLT PET/CT detected changes 
in proliferation, with early increase in SUVmax predicting progressive disease with a 
high specificity and PPV23. 
 
2.0 
STUDY OBJECTIVES 
2.1 
Primary Objectives 
 To assess if percentage change in 18FFLT PET/CT quantitative parameters 
(SUV max, or SUV peak or proliferative tumor volume) after 2 cycles of 
chemotherapy can predict overall survival at 1 and 2 years in patients with 
resectable, borderline resectable or locally advanced pancreatic 
adenocarcinoma. 
2.2 
Secondary Objectives 
 To assess if percentage change in 18FFLT PET/CT quantitative parameters 
(SUV max, or SUV peak or proliferative tumor volume) after 2 cycles of 
chemotherapy can predict progression free survival at 6 months and 1 year 
in patients with resectable, borderline resectable or locally advanced 
pancreatic adenocarcinoma. 
2.3 
Exploratory Objectives 
None 
2.4 
Endpoints 
Primary endpoint is to determine that a positive response (decrease on quantitative 
parameters) at an interim 18F FLT PET/CT (performed after 2 cycles of 
chemotherapy) is related to longer progression free survival and overall survival.  

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3.0 
 SUBJECT ELIGIBILITY 
Eligibility waivers are not permitted. Subjects must meet all of the inclusion and 
exclusion criteria to be registered to the study. Study treatment may not begin until a 
subject is registered. 
3.1 
Inclusion Criteria 
 Patients with histologically confirmed pancreatic adenocarcinoma 
(resectable, borderline resectable or locally advanced disease at 
presentation) are eligible for the study. 
 Patients should not have any type of curative or palliative therapy for 
pancreatic adenocarcinoma before enrolling in the study  and should be 
candidates for induction chemotherapy. 
 Patients must be over 18 years old and capable and willing to provide 
informed consent. 
  Patients must have measurable disease (by RECIST 1.1 criteria) 
 Patients must have an ECOG performance status of 0-3 (restricted to ECOG 
PS 0-2 if age >70 years).  
 Patients of childbearing potential must have a negative urine or serum 
pregnancy test within 7 days prior to the FLT PET/CT and the optional FDG 
PET/CT imaging per institution’s standard of care; A female of child-
bearing potential is any woman (regardless of sexual orientation, having 
undergone a tubal ligation, or remaining celibate by choice) who meets the 
following criteria; 
i. 
Has not undergone a hysterectomy or bilateral oophorectomy; or 
ii. 
Has not been naturally postmenopausal for at least 12 consecutive 
months (i.e., has had menses at any time in the preceding 12 
consecutive months). 
 Medically stable as judged by patient’s physician. 

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 Patients with known allergic or hypersensitivity reactions to previously 
administered radiopharmaceuticals of similar chemical or biologic 
composition to FLT or FDG are NOT eligible.  
 Ability to understand and the willingness to sign a written informed consent. 
 Patient must be able to lie still for a 20 to 30 minute PET/CT scan. 
3.2 
Exclusion Criteria 
 Subjects who had prior chemotherapy or radiotherapy for pancreatic 
adenocarcinoma cannot participate in the study. 
 Patient must NOT be pregnant or breast-feeding. 
 Patients have no clinical evidence of distant metastatic disease 
  Patients must not weigh more than the maximum weight limit for the table 
for the PET/CT scanner where the study is being performed.(>200kg or 
440lbs) 
 
 
4.0 
STUDY PLAN 
 

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N.B: FDG PET/CT can be performed before or after baseline FLT, but must be within 30days of baseline FLT PET/CT. 
 
The experimental 18F-FLT-PET/CT is required to be completed before initiation of 
chemotherapy. Labs and correlative radiology, as directed per clinical care, are required 
within 30 days prior to 18F-FLT-PET/CT; and optional 18F-FDG-PET/CT  within 30 days 
of the 18F-FLT-PET/CT. Follow-up will comprise 24 months of standard practice 
treatment and follow up.  
 
 
Visit 1: Patients will have at least one visit with investigator (or investigator designee) 
prior to the study to review clinical history and prior treatment of pancreatic 
adenocarcinoma, and to explain the study. Correlative radiology studies including CT, 
MRI and/or18F FDG-PET/CT as per institutional routine clinical care, and any clinically-
directed laboratory tests performed as part of staging. All clinical care tests must be 
performed within 30 days of the 18F FLT-PET/CT.The following additional patient data 
will be obtained: histological diagnosis of primary and/or metastatic disease, date of 
diagnosis of primary and no evidence of metastatic disease, gender, height, weight (for 
BMI), ECOG score and confirmation of absence of prior treatment. 
Visit 2(optional): The 18F-FDG-PET/CT may be done as a research scan if patients 
agrees to that, if the patient is unable to obtain a clinically-directed 18F-FDG-PET/CT as 
part of their clinical care or within 30 days of 18F FLT-PET/CT, before or after the 
baseline FLT. The research 18F-FDG-PET/CT, in this instance, will be identical in 
procedure to the institution’s clinical 18F-FDG-PET/CT. The blood glucose level will be 
< 200 mg/dl, before 18F-FDG injection, which is institutional standard clinical protocol.  

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Visit 3: Day of 18F-FLT-PET/CT: The patient will have an intravenous line placed in the 
hand or arm, 18F-FLT-PET/CT will be given by 1-2 minute IV push, and the dose 
administered will be approximately 5 mCi (+/- 20% dose). After approximately 60 +/- 10 
minutes of uptake time, the patient will be positioned supine in the PET/CT scanner for 
standard whole body PET/CT scan from the skull base to mid-thigh. This scan will take 
approximately 20-30 min. The window from FLT PET/CT baseline study to initiation of 
chemotherapy should be no more than 30 days.  
Visit 4: Day of Interim 18F-FLT-PET/CT: The interim 18F FLT-PET/CT will be 
performed after the 2nd cycle of chemotherapy regimen, but before the commencement of 
3rd cycle. The second 18F-FLT-PET/CT study must be performed on the same scanner as 
the first 18F FLT-PET/CT and the imaging protocol described in Visit 3 should be closely 
followed. 
4.1 
Study duration: 
Clinical Follow Up: Standard of care clinical follow-up data will be collected up to 2 
years following the end of chemotherapy.  
5.0 
STUDY PROCEDURES 
5.1 
Screening/Baseline Procedures 
Assessments performed exclusively to determine eligibility for this study will be done 
only after obtaining informed consent. Assessments performed for clinical indications 
(not exclusively to determine study eligibility) may be used for baseline values even if 
the studies were done before informed consent was obtained. 
All screening procedures must be performed within 60 days prior to registration unless 
otherwise stated. The screening procedures include: 
Informed Consent 
Informed consent will be obtained from each research participant by the 
investigator or the study coordinator. No participant will be allowed to participate 
without a signed, IRB-approved, consent form.  
Medical history 
Review of complete medical and surgical history  available in the electronic medical 
system at UT Southwestern Medical Center   
Demographics: Age, gender, race, ethnicity 
Review subject eligibility criteria 
Review previous and concomitant medications  
Available in the electronic medical system at UT Southwestern   
Review of Physical exam including vital signs, height and weight 
Vital signs (temperature, pulse, respirations, blood pressure), height, weight 

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Performance status 
Review of ECOG Performance status evaluated prior to study entry. 
Serum chemistries 
Review of metabolic panel (CMP) to include (if available): albumin, alkaline 
phosphatase, ALT/SGPT, AST/SGOT, BUN, creatinine, electrolytes (sodium, potassium, 
calcium, chloride, bicarbonate), glucose, and total bilirubin.. Only labs ordered as 
standard of care and available in EMR (EPIC) at time of screening will be reviewed, new 
labs will not be ordered for research. 
Pregnancy test (for females of child bearing potential) 
See section 3.1.e. for definition.  
 
5.2 
Time and Events Table  
SAMPLE 
Visit 1: 
screening 
Visit 2(optional): 
18F FDG PET/CT 
staging (if needed 
for research) 
Visit 3: 18F 
FLT PET/CT 
Visit 4: 
Interim 18F 
FLT PET/CT 
Follow-up 
Informed Consent 
X 
 
 
 
 
Demographics 
X 
 
 
 
 
Clinical history 
X 
 
 
 
 
Height/weight 
X 
X 
X 
X 
 
Physical exam 
X 
 
 
 
 
Survival/patient status 
 
 
 
 
X 
Review biopsy records 
X 
 
 
 
 
18F FLT PET/CT 
 
 
X 
X 
 
18F FDG PET/CT 
(optional) 
 
X 
 
 
 
Other radiologic studies 
(CT or MRI) 
X 
 
 
 
X 
Pre-scan pregnancy test (if 
needed) 
 
X 
X 
X 
 
Adverse event 
evaluation 
 
 
X 
X 
 
5.3 
Removal of Subjects from Study 
Subjects can be taken off the study treatment and/or study at any time at their own request, 
or they may be withdrawn at the discretion of the investigator for safety, behavioral or 

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administrative reasons. The reason(s) for discontinuation will be documented and may 
include: 
 Subject withdraws consent (termination of treatment and follow-up); 
 Subject is unable to comply with protocol requirements; 
 The researchers believe that participation in the research is no longer safe 
for the subject; 
 Subject experiences toxicity that makes continuation in the protocol unsafe; 
 Treating physician judges continuation on the study would not be in the 
subject’s best interest; 
 Subject becomes pregnant (pregnancy to be reported along same timelines 
as a serious adverse event); 
5.4 
Safety 
As with all PET imaging agents, 3'-deoxy-3'-[18F]-fluorothymidine is a 
radiopharmaceutical that decays with positron emission. As such, it poses an intrinsic 
radiation exposure risk. However, this risk is felt to be extremely small, at the doses 
administered in this study. The organ and total body doses associated with FLT PET 
imaging are comparable to or lower than those associated with other widely used clinical 
nuclear medicine procedures. 
 
The radiation absorbed effective dose equivalent to the whole body from intravenously 
injected 18F-FLT is estimated to be 0.028±0.012 mSv/MBq. The total body doses 
associated with 18F-FLT PET imaging are comparable to or lower than those associated 
with other widely used clinical nuclear medicine procedures and are well below the 
maximum suggested for individual study and annual total body dose of 30 and 50 mGy, 
respectively, suggested for investigational radiopharmaceuticals by the FDA.  
The usual risks of PET studies include those due to IV line. The IV line risks are bleeding 
or a possible hematoma at the sight of injection. A physician will be available to 
document the adequacy of the venous line and provide assistance in case of inadvertent 
tracer extravasations or hematoma formation. 
All adverse events occurring within a 24-hour period post-FLT infusion will be recorded. 
The adverse events to be specifically monitored during the infusion include localized 
discomfort at the IV injection site, pain, respiratory difficulties, flushing, dizziness, 
pruritus/rash, and any other symptoms that could be secondary to an anaphylactic 
reaction. The subject will be instructed to report any subjective symptoms or sensory 
changes noted. 
 
 

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6.0 
Measurement of Effect 
6.1 
Antitumor Effect- Solid Tumors 
Response and progression will be evaluated in this study using the new international 
criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) 
Committee24. Changes in only the largest diameter (unidimensional measurement) of the 
tumor lesions are used in the RECIST v1.1 criteria.  
This evaluation will be done at the CT or MRI by the end of chemotherapy and in follow 
up CT or MRI, performed as standard of care (up to 2 years). This information will be 
used for assessment of progression free survival at 6 months and at 1 year. 
6.2 
Disease Parameters 
Measurable disease. Measurable lesions are defined as those that can be accurately 
measured in at least one dimension (longest diameter to be recorded) as >20 mm with 
conventional techniques (CT, MRI, x-ray) or as >10 mm with spiral CT scan. All tumor 
measurements must be recorded in millimeters (or decimal fractions of centimeters). 
Note: Previously irradiated lesions are non-measurable except in cases of documented 
progression of the lesion since the completion of radiation therapy. 
 
Non-measurable disease. All other lesions (or sites of disease), including small lesions 
(longest diameter <20 mm with conventional techniques or <10 mm using spiral CT 
scan), are considered non-measurable disease. Bone lesions, leptomeningeal disease, 
ascites, pleural/pericardial effusions, lymphangitis cutis/pulmonis, inflammatory breast 
disease, abdominal masses (not followed by CT or MRI), and cystic lesions are all non-
measurable. 
Target lesions. All measurable lesions up to a maximum of 3 lesions per organ and 6 
lesions in total, representative of all involved organs, should be identified as target 
lesions and recorded and measured at baseline. Target lesions should be selected on the 
basis of their size (lesions with the longest diameter) and their suitability for accurate 
repeated measurements (either by imaging techniques or clinically). A sum of the longest 
diameter (LD) for all target lesions will be calculated and reported as the baseline sum 
LD. The baseline sum LD will be used as reference by which to characterize the objective 
tumor response. 
 
Non-target lesions. All other lesions (or sites of disease) including any measurable 
lesions over and above the 6 target lesions should be identified as non-target lesions and 

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should also be recorded at baseline. Measurements of these lesions are not required, but 
the presence or absence of each should be noted throughout follow-up.  
6.3 
Methods for Evaluation of Measurable Disease 
All measurements should be taken and recorded in metric notation using a ruler or 
calipers. All baseline evaluations should be performed as closely as possible to the 
beginning of treatment and never more than 28 days before the beginning of the 
treatment. 
 
The same method of assessment and the same technique should be used to characterize 
each identified and reported lesion at baseline and during follow-up. Imaging-based 
evaluation is preferred to evaluation by clinical examination when both methods have 
been used to assess the antitumor effect of a treatment. 
 
Conventional CT and MRI:  Standard of care spiral CT will be performed with 
intravenous contrast (whenever possible) using a 5 mm contiguous reconstruction 
algorithm. MRI of the abdomen will be performed with intravenous contrast (also 
whenever possible) with multiple T1 and T2 weighted multiplanar sequences and 
volumetric dynamic post contrast images.  
6.4 
Response Criteria 
6.4.1 
Evaluation of Target Lesions 
Complete Response (CR): Disappearance of all target lesions, determined by two 
separate observations conducted not less than 4 weeks apart. There can be no appearance 
of new lesions. 
 
Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) 
of target lesions, taking as reference the baseline sum LD. There can be no appearance of 
new lesions. 
 
Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, 
taking as reference the smallest sum LD recorded since the treatment started, or the 
appearance of one or more new lesions. 
 
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase 
to qualify for PD, taking as reference the smallest sum LD since the treatment started. 

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6.4.2 
Evaluation of Non-Target Lesions 
Complete Response (CR): Disappearance of all non-target lesions and normalization of 
tumor marker level. 
 
Incomplete Response/Stable Disease (SD): Persistence of one or more non-target 
lesion(s) and/or maintenance of tumor marker level above the normal limits. 
 
Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal 
progression of existing non-target lesions 
6.4.3 
Evaluation of Best Overall Response 
The best overall response is the best response recorded from the start of the treatment 
until disease progression/recurrence (taking as reference for progressive disease the 
smallest measurements recorded since the treatment started). The subjects best response 
assignment will depend on the achievement of both measurement and confirmation 
criteria. 
 
 
Target 
Lesions 
Non-Target 
Lesions 
New Lesions 
Overall 
Response 
Best Response for this 
Category Also Requires: 
CR 
CR 
No 
CR 
>4 wks. confirmation 
CR 
Non-CR/Non-
PD 
No 
PR 
>4 wks. confirmation 
PR 
Non-PD 
No 
PR 
SD 
Non-PD 
No 
SD 
Documented at least 
once >4 wks. from 
baseline 
PD 
Any 
Yes or No 
PD 
No prior SD, PR or CR 
Any 
PD* 
Yes or No 
PD 
Any 
Any 
Yes 
PD 

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* 
In exceptional circumstances, unequivocal progression in non-target lesions may be 
accepted as disease progression. 
 
Note: Subjects with a global deterioration of health status requiring discontinuation of 
treatment without objective evidence of disease progression at that time should be reported as 
“symptomatic deterioration”. Every effort should be made to document the objective 
progression even after discontinuation of treatment. 
 
Note: If subjects respond to treatment and are able to have their disease resected, the 
patient’s response will be assessed prior to the surgery. 
6.4.4 
Duration of Response 
Duration of overall response: The duration of overall response is measured from the time 
measurement criteria are met for CR or PR (whichever is first recorded) until the first 
date that recurrent or progressive disease is objectively documented (taking as reference 
for progressive disease the smallest measurements recorded since the treatment started). 
 
The duration of overall CR is measured from the time measurement criteria are first met 
for CR until the first date that recurrent disease is objectively documented.  
 
Duration of stable disease: Stable disease is measured from the start of the treatment until 
the criteria for progression are met, taking as reference the smallest measurements 
recorded since the treatment started.  
6.4.5 
Progression-Free Survival 
Progression-free survival (PFS) is defined as the duration of time from start of treatment 
to time of progression. 
 
6.5 
Safety/tolerability 
 
Analyses will be performed for all subjects having received at least one dose of 
study drug. The study will use the CTCAE version 4.0 for reporting of non-hematologic 
adverse events (http://ctep.cancer.gov/reporting/ctc.html) and modified criteria for 
hematologic adverse events. 
7.0 
ADVERSE EVENTS 
7.1 
Adverse Event Monitoring 
Adverse event data collection and reporting, which are required as part of every clinical 
trial, are done to ensure the safety of subjects enrolled in the studies as well as those who 

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will enroll in future studies using similar agents. Adverse events are reported in a routine 
manner at scheduled times during a trial. Additionally, certain adverse events must be 
reported in an expedited manner to allow for optimal monitoring of subject safety and 
care.  
 
All subjects experiencing an adverse event, regardless of its relationship to study drug, 
will be monitored until:  
• the adverse event resolves or the symptoms or signs that constitute the adverse 
event return to baseline; 
• any abnormal laboratory values have returned to baseline; 
• there is a satisfactory explanation other than the study drug for the changes 
observed; or 
• death. 
 
 
Definition  
Adverse Events will be reported as indicated by the appropriate following table (see 
below).    
An adverse event is defined as any untoward or unfavorable medical occurrence in a 
human research study participant, including any abnormal sign (for example, abnormal 
physical exam or laboratory finding), symptom, clinical event, or disease, temporarily 
associated with the subject’s participation in the research, whether or not it is considered 
related to the subject’s participation in the research. 
Adverse events encompass clinical, physical and psychological harms. Adverse events 
occur most commonly in the context of biomedical research, although on occasion, they 
can occur in the context of social and behavioral research. Adverse events may be 
expected or unexpected. 
 
 
Severity  
Adverse events will be graded by a numerical score according to the defined NCI 
Common Terminology Criteria for Adverse Events (NCI CTCAE) and version number 
specified in the protocol. Adverse events not specifically defined in the NCI CTCAE will 
be scored on the Adverse Event log according to the general guidelines provided by the 
NCI CTCAE and as outlined below.   
• Grade 1: Mild  

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• Grade 2: Moderate 
• Grade 3: Severe or medically significant but not immediately life threatening 
• Grade 4: Life threatening consequences 
• Grade 5: Death related to the adverse event 
 
 
Serious Adverse Events  
ICH Guideline E2A and the UTSW IRB define serious adverse events as those events, 
occurring at any dose, which meets any of the following criteria:  
• Results in death   
• Immediately life-threatening  
• Results in inpatient hospitalization or prolongation of existing hospitalization  
• Results in persistent or significant disability/incapacity  
• Results in a congenital anomaly/birth defect  
• Based upon appropriate medical judgment, may jeopardize the subject’s health 
and may require medical or surgical intervention to prevent one of the other 
outcomes listed in this definition. 
 
Note: A “Serious adverse event” is by definition an event that meets any of the above 
criteria. Serious adverse events may or may not be related to the research project. A 
serious adverse event determination does not require the event to be related to the 
research. That is, both events completely unrelated to the condition under study and 
events that are expected in the context of the condition under study may be serious 
adverse events, independent of relatedness to the study itself. As examples, a car accident 
requiring overnight hospitalization would be a serious adverse event for any research 
participant; Likewise, in a study investigating end-stage cancer care, any hospitalization 
or death which occurs during the protocol-specified period of monitoring for adverse and 
serious adverse events would be a serious adverse event, even if the event observed is a 
primary clinical endpoint of the study. 
 
All serious adverse events occurring within a 24-hour period post-FLT infusion will be 
recorded. 

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Unanticipated Problems Involving Risks to Subjects or Others (UPIRSOs): 
The term “unanticipated problem” is found, but not defined in the regulations for the 
Protection of Human Subjects at 45 CFR 46, and the FDA regulations at 21 CFR 56. 
Guidance from the regulatory agencies considers unanticipated problems to include any 
incident, experience, or outcome that meets each of the following criteria: 
• 
Unexpected (in terms of nature, severity or frequency) AND 
• 
Definitely or probably related to participation in the research AND  
• 
Serious or a possible unexpected problem in that the research places subjects or 
others at greater risk of harm than was previously known or recognized. Note: 
Any serious adverse event would always suggest a greater risk of harm. 
 
Follow-up  
All adverse events will be followed up according to good medical practices.  
 
Reporting 
The UTSW IRB requires reporting of all UPIRSOs according to the guidance below. For 
participating centers other than UTSW, local IRB guidance should be followed for local 
reporting of serious adverse events. All SAEs occurring during the protocol-specified 
monitoring period should be submitted to the UTSW study team within 2 business days 
of the center learning of the event. 
7.2.3.1 UPIRSOs occurring on the study require expedited reporting, and are submitted to 
the UTSW IRB through the UTSW eIRB by the UTSW study team and to the SCCCC 
DSMC Coordinator.  Hardcopies or electronic versions of the eIRB report; FDA Form 
#3500A forms, or other sponsor forms, if applicable; and/or any other supporting 
documentation available should be submitted to the UTSW study team and will be 
forwarded to the DSMC Coordinator.  The DSMC Coordinator forwards the information 
onto the DSMC Chairman who determines if immediate action is required.  Follow-up 
eIRB reports, and all subsequent SAE documentation that is available are also submitted 
to the DSMC Chair who determines if further action is required. (See Appendix IV of the 
SCCCC DSMC Plan for a template Serious Adverse Event Form which may be utilized 
when a sponsor form is unavailable and SAE submission to the eIRB is not required). 
  
All serious adverse events which occur on research subjects on protocols for which the 
SCCCC is the DSMC of record require reporting to the DSMC regardless of whether IRB 
reporting is required. Hardcopies or electronic versions of the FDA Form #3500A forms, 
or other sponsor forms, if applicable; and/or any other supporting documentation 
available should be forwarded to the DSMC Coordinator.   
 
 
 

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SAEs 
Serious adverse events (SAEs) for studies where Simmons Cancer Center (SCCC) Data 
Safety Monitoring Committee (DSMC) is the DSMC of record, requires reporting to the 
DSMC coordinator within 2 working days of PI awareness, or as described in the 
protocol.   
 
Unanticipated Problems Involving Risks to Subjects or Others (UPIRSOs) 
Local Serious Adverse Event UPIRSOs require reporting to the UTSW 
IRB within 48 hours of PI awareness of the event (life threatening or fatal 
events experienced by subjects Steps to Determine If an Adverse Event 
Requires Expedited Reporting 
Step 1: Identify the type of adverse event using the NCI Common Terminology Criteria 
for Adverse Events (CTCAE v4).  
 
Telephone reports to: 
(Investigator/study team: Dr. Pinho, Telephone: 214-648-5489) 
 
 
Written reports to: 
(Investigator/study team: Dr. Pinho, Telephone: 214-648-5489, Fax: 214-648-7352, 
email: Daniella.Pinho@Utsouthwestern.edu) 
 
UTSW SCC Data Safety Monitoring Committee Coordinator 
Email: SCCDSMC@utsouthwestern.edu 
Fax: 214-648-5949 or deliver to BLB.306 
 
UTSW Institutional Review Board (IRB) 
Submit via eIRB with a copy of the final sponsor report as attached supporting 
documentation 
 
 

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Step 2: Grade the adverse event using the NCI CTCAE v4. 
 
Step 3: Determine whether the adverse event is related to the protocol therapy  
Attribution categories are as follows: 
• Definite – The AE is clearly related to the study treatment. 
• Probable – The AE is likely related to the study treatment. 
• Possible – The AE may be related to the study treatment. 
• Unrelated – The AE is clearly NOT related to the study treatment. 
. 
 
Step 4: Determine the prior experience of the adverse event.  
Expected events are those that have been previously identified as resulting from 
administration of the agent. An adverse event is considered unexpected, for expedited 
reporting purposes only, when either the type of event or the severity of the event is not 
listed in: 
• the current known adverse events listed in the Agent Information Section of 
this protocol; 
• the drug package insert; 
• the current Investigator’s Brochure 
8.0 
DRUG INFORMATION 
3’-deoxy-3’-[18F]-fluorothymidine 
Other names for the drug(s): 18F FLT  
Classification - type of agent: Radiopharmaceutical  
Mode of action: Fluorothymidine is an analog of the nucleoside thymidine 
(deoxythymidine) but the 3’-F atom prevents FLT from following the full biochemical 
pathway of thymidine. Once in the cell, FLT is a substrate for thymidine kinase I (TK1) 
and is phosphorylated but is not incorporated into DNA.  
Protocol dose: 5 mCi (+/- 20%) 
Preparation: Provided as unit dose by the UTSW cyclotron facility to inject into 
patients. FLT is administered to subjects by intravenous injection of ≤ 10 mL. The drug 

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solution is stored at room temperature in a gray butyl septum sealed, sterile, pyrogen-free 
glass vial and has an expiration time of 8 hours. 
Route of administration for this study: intravenous 
Incompatibilities: no known incompatibilities  
Availability: Produced at the UT Southwestern Cyclotron facility under an FDA IND 
Side effects:  
No adverse events have been attributed to Positron-Emission Tomography (PET) 
imaging/diagnostic administration of [3'-deoxy-3'-[18F]fluorothymidine (FLT) at the 
levels injected. Therefore, no adverse events are expected as a result of the intravenous 
(IV) administration of 18F FLT. 
As with many intravenously administered agents, 3'-deoxy-3'-[18F] fluorothymidine could 
cause an allergic reaction that could potentially pose a threat to life (anaphylaxis). This 
has not been observed in limited human exposure to date. Reasonable precautions will be 
taken, consistent with normal radiologic and clinical facility practice. The patient will be 
monitored until the PET procedure is completed, and trained personnel will be available 
per facility standards. 
 
9.0 
STATISTICAL CONSIDERATIONS 
 
9.1 
Study Design/Study Endpoints 
 
We anticipate to enroll 20 patients with biopsy proven pancreatic adenocarcinoma 
that are not eligible for resection by the time of the diagnosis. These patients are going to 
be treated with chemotherapy only or chemoradiation in selected cases. These patients 
will undergo an optional18F FDG PET/CT (as standard of care clinical baseline) and 18F-
FLT PET/CT before treatment (research baseline study), and after two cycles of 
chemotherapy (research early therapy assessment study).   
 
For the 18F-FLT PET/CT analysis, SUV max, SUV peak and proliferative tumor 
volume will be measured by MIMvista software and compared between the two studies. 
Tumor size and extension will also be evaluated on CT images from the PET/CT study.  
At completion of treatment (6 months after baseline  FLT PET/CT) an anatomic study 
(MRI or CT) will be performed as standard of care in our institution to reassess the tumor 
and classify it as ressectable or non-ressectable. Also at 6 months, 1 year and 2 years after 
initial baseline scan, or before if clinically indicated, standard of care anatomic study 
(MRI or CT) will also be performed and will be revaluated by RECIST criteria to 
determine stability versus progression of disease. 

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9.2 
Sample size 
The sample size was based on an ability to detect a relative group difference in FLT SUV 
(baseline versus interim) of 0.124 and standard deviation of 0.17. A sample size of 15 
patients was calculated using a two-sided paired t test, power of 80 %, and the type I 
error rate was set to be 0.05. The expected response to therapy was assumed to be 
20%18,23,25. 
Five patients were added to the sample size to compensate for dropout and no uptake on 
the baseline scan, leading to a total sample size of 20. 
 
9.3 
Data Analyses Plans 
 
Primary outcome variable: The difference in SUVmax, SUVpeak and 
proliferative tumor volume between baseline and 2 cycles of chemotherapy will be 
correlated with overall survival at 1 and 2 years and with progression free survival at 6 
months and at 1 year. 
 
The primary outcome of the study is to establish which degree of change in the 
PET/CT quantitative parameters can predict patients overall survival and progression free 
survival. The SUVmax (representing the single voxel with the highest activity 
concentration), SUV peak (which is defined as the average SUV within a 1 cubic cm 
volume within the region of the tumor with the highest metabolic activity) and 
proliferative tumor volume of the pancreatic tumor will be measured.  
 
Univariate and multiple cox regression model are going to be used. P-value less 
than 0.05 will be considered as statistical significant. 
 
Secondary outcome variable: the difference in SUVmax, SUVpeak and 
proliferative tumor volume between baseline and 2 cycles of chemotherapy will be 
correlated with binary tumor outcome measured from MRI/CT (resectable versus non-
resectable disease) at 6 month using logistic regression. A multiple logistic regression 
with stepwise selection algorithm will be used to select the most correlated variable(s). 
Areas under the ROC curve (AUC) and corresponding 95% confidence interval will be 
calculated for all models. Leave one out cross validation will be applied to avoid over-fit. 
10.0 
STUDY MANAGEMENT 
10.1 
Conflict of Interest 
Any investigator who has a conflict of interest with this study (patent ownership, 
royalties, or financial gain greater than the minimum allowable by their institution, etc.) 
must have the conflict reviewed by the UTSW COI Committee and IRB according to 
UTSW Policy on Conflicts of Interest.  All investigators will follow the University 
conflict of interest policy. 

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10.2 
Institutional Review Board (IRB) Approval and Consent 
It is expected that the IRB will have the proper representation and function in accordance 
with federally mandated regulations. The IRB must approve the consent form and 
protocol. 
 
In obtaining and documenting informed consent, the investigator should comply with the 
applicable regulatory requirement(s), and should adhere to Good Clinical Practice (GCP) 
and to ethical principles that have their origin in the Declaration of Helsinki. 
 
 
Before recruitment and enrollment onto this study, the subject will be given a full 
explanation of the study and will be given the opportunity to review the consent form. 
Each consent form must include all the relevant elements currently required by the FDA 
Regulations and local or state regulations. Once this essential information has been 
provided to the subject and the investigator is assured that the subject understands the 
implications of participating in the study, the subject will be asked to give consent to 
participate in the study by signing an IRB-approved consent form. 
 
Prior to a patient’s participation in the trial, the written informed consent form should be 
signed and personally dated by the subject  and by the person who conducted the 
informed consent discussion. 
10.3 
Registration/Randomization Procedures 
There is no randomization in this study. 
 
All subjects must be registered with the Radiology Clinical Trial Office (NE6.120) before 
enrollment to study. Prior to registration, eligibility criteria must be confirmed with the 
Clinical Trial Office Study Coordinator. To register a subject, call 214-645-2717 Monday 
through Friday, 9:00AM-5:00PM.  
Subjects will be registered after PI has confirmed eligibility and study number will be 
generated in velos. 
 
10.4 
Data Management and Monitoring/Auditing 
REDCap is the UTSW SCCC institutional choice for the electronic data capture of case 
report forms for this and all SCCC Investigator Initiated Trials. REDCap will be used for 
electronic case report forms in accordance with SCCC requirements. 
 

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Trial monitoring will be conducted no less than annually and refers to a regular interval 
review of trial related activity and documentation performed by the DOT, which includes 
but is not limited to accuracy of case report forms, protocol compliance, timeless and 
accuracy of Velos entries and AE/SAE management and reporting. Documentation of 
trial monitoring will be maintained along with other protocol related documents and will 
be reviewed during internal audit. 
 
The UTSW SCCC DSMC is responsible for monitoring data quality and patient safety 
for all UTSW SCCC clinical trials.  As part of that responsibility, the DSMC reviews all 
local serious adverse events and unanticipated problems in real time as they are reported 
and reviews adverse events on a quarterly basis. The quality assurance activity for the 
Clinical Research Office provides for periodic auditing of clinical research documents to 
ensure data integrity and regulatory compliance. A copy of the DSMC plan is available 
upon request. 
 
The SCCC DSMC meets quarterly and conducts annual comprehensive reviews of 
ongoing clinical trials, for which it serves as the DSMC of record. The QAC works as 
part of the DSMC to conduct regular audits based on the level of risk. Audit findings are 
reviewed at the next available DSMC meeting. In this way, frequency of DSMC 
monitoring is dependent upon the level of risk. Risk level is determined by the DSMC 
Chairman and a number of factors such as the phase of the study; the type of 
investigational agent, device or intervention being studied; and monitoring required to 
ensure the safety of study subjects based on the associated risks of the study. Protocol-
specific DSMC plans must be consistent with these principles.  
10.5 
Adherence to the Protocol 
Except for an emergency situation in which proper care for the protection, safety, and 
well-being of the study subject requires alternative treatment, the study shall be 
conducted exactly as described in the approved protocol.  
10.6 
Emergency Modifications 
Investigators may implement a deviation from, or a change of, the protocol to eliminate 
an immediate hazard(s) to trial subjects without prior IRB approval.  
 
For any such emergency modification implemented, an IRB modification form must be 
completed within five (5) business days of making the change. 
10.7 
Other Protocol Deviations/Violations 
All other planned deviations from the protocol must have prior approval by the Principal 
Investigator and the IRB. According to the IRB, a protocol deviation is any unplanned 
variance from an IRB approved protocol that:  

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• Is generally noted or recognized after it occurs 
• Has no substantive effect on the risks to research participants 
• Has no substantive effect on the scientific integrity of the research plan or the value 
of the data collected  
• Did not result from willful or knowing misconduct on the part of the 
investigator(s).  
 
An unplanned protocol variance is considered a violation if the variance: 
• Has harmed or increased the risk of harm to one or more research participants. 
• Has damaged the scientific integrity of the data collected for the study. 
• Results from willful or knowing misconduct on the part of the investigator(s). 
• Demonstrates serious or continuing noncompliance with federal regulations, State 
laws, or University policies. 
 
If a deviation or violation occurs without prior approval from the Principal Investigator, 
please follow the guidelines below: 
Protocol Deviations: Personnel will report to any sponsor or data and safety monitoring 
committee in accordance with their policies. Deviations should be summarized and 
reported to the IRB at the time of continuing review. 
 
Protocol Violations: Study personnel should report violations within two (2) week of the 
investigator becoming aware of the event using the same IRB online mechanism used to 
report Unanticipated Problems.  
10.8 
Amendments to the Protocol 
Should amendments to the protocol be required, the amendments will be originated and 
documented by the Principal Investigator. A summary of changes document outlining 
proposed changes as well as rationale for changes, when appropriate, is highly 
recommended. When an amendment to the protocol substantially alters the study design 
or the potential risk to the patient, a revised consent form might be required.  
 
The written amendment, and if required the amended consent form, must be sent to the 
IRB for approval prior to implementation.  

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10.9 
Record Retention 
Study documentation includes all Case Report Forms, data correction forms or queries, 
source documents, Sponsor-Investigator correspondence, monitoring logs/letters, and 
regulatory documents (e.g., protocol and amendments, IRB correspondence and approval, 
signed patient consent forms). 
 
Source documents include all recordings of observations or notations of clinical activities 
and all reports and records necessary for the evaluation and reconstruction of the clinical 
research study. 
 
Government agency regulations and directives require that the study investigator retain 
all study documentation pertaining to the conduct of a clinical trial. In the case of a study 
with a drug seeking regulatory approval and marketing, these documents shall be retained 
for at least two years after the last approval of marketing application in an International 
Conference on Harmonization (ICH) region. In all other cases, study documents should 
be kept on file until three years after the completion and final study report of this 
investigational study. 
10.10 Obligations of Investigators 
The Principal Investigator is responsible for the conduct of the clinical trial at the site in 
accordance with Title 21 of the Code of Federal Regulations and/or the Declaration of 
Helsinki. The Principal Investigator is responsible for personally overseeing the treatment 
of all study patients. The Principal Investigator must assure that all study site personnel, 
including sub-investigators and other study staff members, adhere to the study protocol 
and all FDA/GCP/NCI regulations and guidelines regarding clinical trials both during 
and after study completion. 
 
The Principal Investigator at each institution or site will be responsible for assuring that 
all the required data will be collected and entered onto the Case Report Forms. 
Periodically, monitoring visits may be conducted and the Principal Investigator will 
provide access to his/her original records to permit verification of proper entry of data. At 
the completion of the study, all case report forms will be reviewed by the Principal 
Investigator and will require his/her final signature to verify the accuracy of the data. 
11.0 
REFERENCES 
 
 
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Do not disclose or use except as authorized in writing by the study sponsor. 
 
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Do not disclose or use except as authorized in writing by the study sponsor. 
 
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