Pilot Study of Dynamic Contrast Enhanced Computed Tomography (DCE-CT) Imaging for the Assessment of Radiation Therapy Outcome for Liver Cancer Patients
Phase: EARLY_PHASE1
Conditions: Liver Cancer
Sponsor: University of Colorado, Denver

 
 
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Pilot Study of Dynamic Contrast Enhanced Computed 
Tomography (DCE-CT) Imaging for the assessment of 
radiation therapy outcome for liver cancer patients 
 
 
Protocol Number: 
 
 
18-2874 
Principal Investigator: 
 
 
Moyed Miften, PhD (Radiation Oncology) 
 
 
 
 
 
 
Version Date:   
01/16/2020 
 

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STATEMENT OF COMPLIANCE 
 
This is an investigator-initiated study. The Principal Investigator (PI), Moyed Miften, PhD 
(Radiation Oncology) is conducting the study and acting as the sponsor. As the sponsor-
investigator, both the legal/ethical obligations of a PI and those of a sponsor will be followed. 
 
The trial will be carried out in accordance with Good Clinical Practice (GCP) as required by 
applicable United States (US) laws and applications, including but not limited to United States 
(US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR Part 46, 21 CFR 
Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812). 
 
 
The PI will assure that no changes to the protocol will take place without documented approval 
from the Institutional Review Board (IRB). All personnel involved in the conduct of this study 
have completed Human Subjects Protection Training.  
 
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments.  
 
 
 
Sponsor-Lead Principal Investigator:   
 
 
 
 
 
 
  
 
 
 
 
 
 
                        Print/Type Name  
 
 
Signed:   
 
 
 
 
 
 
 
 
 
Date:    
 
  
 
 

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LIST OF ABBREVIATIONS 
 
ACRONYM 
DESCRIPTION 
IIT  
Investigator-Initiated Trial 
RT 
Radiation Therapy 
DCE-CT 
Dynamic Contrast Enhanced Computed Tomography 
HCC 
Hepatocellular Carcinoma 
 
SBRT 
Stereotactic Body Radiation Therapy 
RECIST 
Response Evaluation Criteria In Solid Tumors 
MRI 
Magnetic Resonance Imaging 
CT 
Computed Tomography 
KTrans 
Volume transfer constant 
SOC 
Standard of Care 
 
 

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PROTOCOL SUMMARY / SYNOPSIS 
Protocol Title: 
Pilot Study of Dynamic Contrast Enhanced Computed Tomography 
(DCE-CT) Imaging for the assessment of radiation therapy outcome 
for liver cancer patients 
 
Objectives: 
 
• Primary Objective: 
Investigate the association between radiation therapy dose 
distribution and change in perfusion measurement following 
treatment. 
• Secondary Objective: 
 
Explore any demographic differences in perfusion metrics. 
 
 
 
Endpoint: 
• Primary Endpoint: 
 
Primary endpoints include therapeutic radiation dose delivered and 
DCE-CT profusion metrics at baseline, following first treatment, and 
6 weeks after treatment. Profusion metrics include: KTrans (aka 
extraction-flow product), blood volume and blood flow. 
 
 
• Secondary Endpoint: 
 
Demographic information (e.g., sex, age, race, etc.) will be combined 
with primary profusion endpoints. 
 
Population: 
• Sample size 
o Maximum number of participants that can be enrolled is 
15 (allow for screen failures)  
o Minimum number of participants to be enrolled 10 
(number of participants needed to answer scientific 
question/aims) 
• Gender Male and Female 
• Age Range 18-100  
• Demographic group We expect patients enrolled on the study to 
have consistent gender, age, racial, and ethnic distributions to the 
population living in the state of Colorado. 
• General health status Liver HCC or Metastases. 
• Geographic location Receiving treatment at UC Metro 

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Phase: 
Pilot 
Number of 
Participating Sites 
enrolling 
participants: 
1 
 
 
Study Duration: 
12 months 
 
 
SCHEMATIC OF STUDY DESIGN 
 
 
 
 
 
 
 
 
 
 
 

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TABLE OF CONTENTS 
STATEMENT OF COMPLIANCE ............................................................................................................................. 2 
LIST OF ABBREVIATIONS ....................................................................................................................................... 3 
PROTOCOL SUMMARY / SYNOPSIS .................................................................................................................... 4 
SCHEMATIC OF STUDY DESIGN .......................................................................................................................... 5 
1 
PARTICIPATING SITES ............................................................................................................................... 8 
2  
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ........................ 8 
2.1  
Background Information .................................................................................................................. 8 
2.2 
Rationale ............................................................................................................................................ 11 
2.3 
Potential Risks and Benefits ........................................................................................................ 12 
2.3.1 
Known Potential Risks ...................................................................................... 12 
2.3.2 
Known Potential Benefits .................................................................................. 13 
3 
OBJECTIVES AND PURPOSE .................................................................................................................. 13 
4 
STUDY DESIGN AND ENDPOINTS ......................................................................................................... 14 
4.1 
Description of the Study Design .................................................................................................. 14 
4.2 
Study Endpoints .............................................................................................................................. 15 
4.2.1 
Primary Endpoints ............................................................................................. 15 
4.2.2 
Secondary Endpoint .......................................................................................... 15 
5 
STUDY ENROLLMENT AND WITHDRAWAL ......................................................................................... 16 
5.1 
Participant Inclusion Criteria ........................................................................................................ 16 
5.2 
Participant Exclusion Criteria ...................................................................................................... 16 
5.3 
Strategies for Recruitment and Retention ................................................................................ 16 
5.4 
Participant Withdrawal or Termination ...................................................................................... 16 
5.4.1 
Reasons for Withdrawal or Termination .......................................................... 16 
5.4.2 
Handling of Participant Withdrawals or Termination ..................................... 17 
5.5 
Premature Termination or Suspension of Study (Study Stopping Rules) ........................ 17 
6 
STUDY AGENT ............................................................................................................................................ 17 
6.1 
Study Agent(s) and Control Description ................................................................................... 17 
7 
STUDY PROCEDURES AND SCHEDULE .............................................................................................. 18 
7.1 
Study Procedures/Evaluations .................................................................................................... 18 
7.2 
Study Schedule ................................................................................................................................ 19 
7.2.1 
Screening ............................................................................................................ 19 
7.2.2 
Enrollment/Baseline .......................................................................................... 19 
7.2.3 
Follow-up ............................................................................................................ 19 
7.2.4 
Final Study Visit ................................................................................................. 19 
7.2.5 
Early Termination Visit ...................................................................................... 20 
7.2.6 
Unscheduled Visit .............................................................................................. 20 
7.2.7 
Schedule of Events Table ................................................................................. 20 
7.4 
Prohibited Medications, Treatments, and Procedures .......................................................... 21 
8 
ASSESSMENT OF SAFETY ...................................................................................................................... 21 
8.1 
Specification of Safety Parameters ............................................................................................ 21 
8.1.1 
Definition of Adverse Events (AE).................................................................... 21 
8.1.2 
Definition of Serious Adverse Events (SAE) ................................................... 21 
8.1.3 
Definition of Unanticipated Problems (UAP) ................................................... 22 
8.2 
Classification of an Adverse Event ............................................................................................. 22 
8.2.1 
Severity of Event ................................................................................................ 22 
8.2.2 
Relationship to Study intervention .................................................................. 22 

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8.2.3 
Expected ADVERSE EVENTS ........................................................................... 23 
8.3 
Time Period and Frequency for Event Assessment and Follow-Up .................................. 23 
8.4 
Reporting Procedures .................................................................................................................... 23 
8.4.1 
Adverse Event Reporting .................................................................................. 23 
8.4.2 
Serious Adverse Event Reporting .................................................................... 23 
8.4.3 
Unanticipated Problem Reporting .................................................................... 24 
8.5 
Study Halting Rules ........................................................................................................................ 24 
8.6 
Safety Oversight .............................................................................................................................. 24 
9 
CLINICAL MONITORING ............................................................................................................................ 25 
10 
STATISTICAL CONSIDERATIONS .......................................................................................................... 25 
10.1 
Statistical and Analytical Plans ................................................................................................... 25 
10.2 
Statistical Hypotheses ................................................................................................................... 26 
10.3 
Analysis Datasets ............................................................................................................................ 26 
10.4 
Description of Statistical Methods .............................................................................................. 26 
10.4.1 
 General Approach ............................................................................................. 26 
10.4.2 
 Analysis of the Primary Efficacy Endpoint(s) ................................................ 26 
10.4.3 
 Analysis of the Secondary Endpoint(s) .......................................................... 27 
10.4.4 
 Safety Analyses ................................................................................................ 27 
10.4.5 
 Adherence and Retention Analyses ............................................................... 27 
10.4.6  
Baseline Descriptive Statistics ......................................................................... 27 
10.4.7 
 Planned Interim Analyses ................................................................................ 27 
10.5 
Sample Size ....................................................................................................................................... 27 
11 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS ................................... 28 
12 
QUALITY ASSURANCE AND QUALITY CONTROL .............................................................................. 28 
13 
ETHICS/PROTECTION OF HUMAN SUBJECTS ................................................................................... 29 
13.1 
Ethical Standard .............................................................................................................................. 29 
13.2 
Institutional Review Board ............................................................................................................ 29 
13.3 
Informed Consent Process ........................................................................................................... 29 
13.3.1 
Consent/assent and Other Informational Documents Provided to 
Participants 
30 
13.3.2 
Consent Procedures and Documentation ....................................................... 30 
13.4 
Participant and Data Confidentiality ........................................................................................... 30 
14 
DATA HANDLING AND RECORD KEEPING .......................................................................................... 31 
14.1 
Data Collection and Management Responsibilities ................................................................ 31 
14.2 
Study Records Retention .............................................................................................................. 32 
14.3 
Protocol Deviations ........................................................................................................................ 32 
16 
CONFLICT OF INTEREST POLICY .......................................................................................................... 33 
17  
LITERATURE REFERENCES.................................................................................................................... 33 
18  
APPENDICES ............................................................................................................................................... 34 
 
 
 

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1 
PARTICIPATING SITES 
A complete and current listing of investigators, research personnel, research facilities and other 
study centers (if applicable) participating in this study will be maintained throughout the duration 
of this study.  
 
2  
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC 
RATIONALE                                     
2.1  
BACKGROUND INFORMATION  
The proposed study is in the field of radiation oncology, where functional imaging will be used to 
assess the outcome of radiation therapy (RT) for liver cancer patients. 
 
Radiation therapy for liver cancer 
 
Liver cancer is a prevalent public health problem. The number of new liver cancer cases was 
estimated to be 39,000 in 2016. Furthermore, liver cancer was estimated to represent 
approximately 5% of all cancer deaths in 2016. The five-year survival rate of all liver cancers is 
estimated to be 18% [1]. Liver cancer is comprised of intrahepatic bile duct cancers (25%) and 
hepatic cell carcinomas (75%). Since less than 25% of hepatic cell carcinomas are eligible for 
surgical resection, radiation therapy is a treatment option for many liver cancer patients [2,3]. 
However, therapy success is suboptimal. Optimization of cancer therapy based on a patient’s 
unique biological characteristics, called “personalized cancer therapy”, is becoming achievable 
[4]. One aspect of the patient’s unique tumor microenvironment is the characteristics of blood 
perfusion. Though there are several imaging modalities that can quantify perfusion, DCE-CT is 
one accessible option. In addition, this study focuses on using SBRT as the radiation therapy 
treatment modality. SBRT delivers radiation therapy over a short time interval (typically, 3-8 
sessions). This differs from conventional external beam radiation therapy, where a typical 
treatment course can last anywhere from 10 to 30 sessions, or more (this is dependent on the total 
radiation dose to the tumor). Historical experiences using large-field liver RT have had limited 
success, because tolerable doses of whole-liver RT (approximately 30 Gy) are insufficient to 
control most lesions [5-7]. Higher doses of whole-liver RT are associated with a significant risk 
of radiation-induced liver damage. Recent data have demonstrated that high-dose partial liver RT 
and SBRT may be safer and more effective than whole-liver RT for patients with liver tumors [8- 
12]. 
 
 
 

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The smaller number of treatment session associated with SBRT helps to reduce patient burden, 
and may have unique biological effect on the tumor vasculature not found in the conventional 
form of radiation therapy [13]. McCammon et al [14] demonstrated a dose-effect for liver 
tumors. They showed increased dose and smaller gross tumor volume were significant predictors 
of higher local control. Lesions treated to a nominal dose of 54 Gy or greater had a 3-year 
actuarial local control rate of 89.3% compared with 59.0% and 8.1% for those treated to 36–53.9 
Gy and less than 36 Gy. On multivariate analysis, only increased dose retained statistical 
significance. 
 
DCE-CT for radiation therapy 
 
Blood flow is a vital characteristic of the tumor microenvironment. Before treatment, perfusion 
may help to predict whether patients will respond to therapy. Measuring change in perfusion after 
therapy may be used to assess the success of therapy. Assessment of SBRT is traditionally 
accomplished using change in tumor morphology, using the RECIST criteria [15]. However, this 
is problematic because tumor volume change does not necessarily describe change in tumor 
physiology. In addition, large necrotic regions of tissue may be included in the morphological 
quantification [16].  
 
Quantification of tumor perfusion has been accomplished in several modalities including MRI and 
CT [17,18]. Recent advances in scanner and image quality has made CT a viable modality for the 
quantification of perfusion in Oncology. Some of the advantages of measuring perfusion with CT 
instead of MRI include, but are not limited to: increased spatial resolution, decreased scan time, 
and study and scanner cost.   
  
Perfusion is the transport of blood to a unit volume of tissue per unit of time and usually refers to 
the blood transport at the capillary level. CT perfusion is based on the increase and subsequent 
decrease of contrast agent concentrations in tissues as a function of time. The typical CT perfusion 
protocol consists of a pre-contrast image acquisition followed by dynamic image acquisitions 
performed sequentially after intravenous injection of an iodinated CT contrast agent. This allows 
the temporal changes in CT attenuation in the tissue volume of interest to be measured. Modern 
CT scanners (>16slices) allow scanning of large volumes of liver tumors, including the portal vein. 
The tissue enhancement measured after contrast material injection can be divided into two 
temporal phases. In the first phase, the enhancement is mainly due to the contrast material within 
the intravascular space, and thus the enhancement is determined by the blood flow. In the second 
phase, tissue enhancement results as contrast material passes from the intravascular to the 
extravascular-extracellular space, and thus the enhancement depends on the blood volume and the 
permeability of capillaries to the contrast agent.  
 

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After CT data acquisition, various CT perfusion parameters can be calculated. Image processing 
is performed to correct for motion during the scan, and manual selection of arterial (and/or portal) 
input functions and ROI definition allows model-based voxel wise computation of perfusion 
parameters. The effective time-intensity curve obtained from liver tissue is a result of an overlay 
of both the arterial and the portal venous components of perfusion. The normal liver is 
predominantly supplied by the low-pressure portal vein (75%) and supplemented by high-pressure 
hepatic artery (25%), but HCC or metastatic liver tumors can lead to global or regional perfusion 
changes. For example, patients with HCC may display increased hepatic arterial flow from the 
appearance of unpaired arteries. In the case of hepatic metastasis, proliferation of endothelial cells 
may result in increased hepatic arterial flow. 
 
CT Perfusion Parameters 
 
To obtain CT perfusion parameters, several kinetic model-based approaches have been developed. 
Single-compartment models allow for estimates of blood flow, blood volume, and MTT. Blood 
flow refers to the volume flow rate of blood through the vasculature (mL/min/100 mL). Blood 
volume is the volume of blood within the vasculature that is actually flowing (mL/100 mL). MTT 
is average time it takes for blood to traverse between the arterial inflow and the venous outflow, 
measured in seconds. Dual-compartment models are necessary to extract parameters that describe 
the interstitial space. Permeability surface area product is the product of permeability and the total 
surface area of capillary endothelium in a unit mass of tissue or tumor (measured as mL/min/100 
mL). Flow extraction product is the product of blood flow and the extraction fraction, which is the 
fraction of contrast agent arriving at the tissue that leaks into the extravascular space in a single 
passage through the vasculature (measured as mL/min/100 mL). 
 
CT perfusion parameters can thus be related to the pathologic features of tumor angiogenesis, 
although the relationship is complex. Blood volume and blood flow are known to correlate with 
microvessel density within the tumor. Blood volume reflects the density of tumor microvessels, 
and is not affected by cardiac output. Permeability-related values such as permeability surface area 
product and flow extraction product are surrogates for vascular leakiness directly related to poorly 
formed vascular basement membrane. Decreased MTT usually reflects the presence of 
arteriovenous shunts, which are frequently demonstrated in the tumor. 
 
The utility of perfusion falls under two categories: prediction of toxicity following radiation 
therapy, and outcome assessment as measured by dose response from radiation therapy treatment. 
Perfusion will characterized for a number of different parameters from a pharmacokinetic model. 
Multiple pharmacokinetic models can describe perfusion. For completeness, we will examine 
several models including: tissue homogeneity, Tofts, extended Tofts, and Patlak. Model goodness 
of fit will be assessed with root mean square error. The following perfusion parameters, derived 

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from previously mentioned pharmacokinetic models, will be quantified for each DCE-CT session: 
blood flow, blood volume of vascular space, blood volume of extracellular space, and intra-
compartment plasma flow. For each model, these perfusion parameters will have the mean, 
extremums, and standard deviation of each parameter value calculated. 
 
The utilization of DCE-CT for outcome assessment in RT has been previously studied in several 
cancer sites, including the liver.  However, no study, to the best of our knowledge, has attempted 
to use DCE-CT as an outcome assessment tool for SBRT treatment of liver cancer. This study aims 
to gather preliminary data to assess the feasibility of using change in perfusion measurements 
following SBRT of liver cancer for outcome assessment. In this study, outcome assessment will 
be done using therapeutic radiation dose delivered as a surrogate measurement for treatment 
response. With the assumption that there is a positive relationship between treatment response and 
therapeutic radiation dose delivered, should this prove feasible, data captured in this study will be 
used to power a larger study aimed at developing a model that uses perfusion measurements for 
outcome assessment and prediction of prognosis following SBRT treatment. 
 
2.2 
RATIONALE  
We are proposing a pilot study to evaluate the feasibility of Dynamic Contrast Enhanced 
Computed Tomography (DCE-CT) imaging for outcome assessment of radiation therapy (RT) for 
the treatment of liver HCC and metastases. DCE-CT, also known as perfusion CT, is a functional 
imaging modality that uses repeated computed tomography imaging after injection of an iodine-
based contrast agent. DCE-CT allows for a quantitative assessment of blood flow in malignant 
solid tumors and healthy surrounding tissue. This data provides for patient-specific information 
about the blood-flow characteristics of the tumor, as well as surrounding healthy tissue. The goal 
of this study is to use each patient’s tumor perfusion information for outcome assessment of 
radiation therapy for the treatment of liver HCC and metastases. 
 
In this study, we propose to focus on Stereotactic Body Radiation Therapy (SBRT) as the radiation 
therapy treatment modality. SBRT delivers radiation therapy over a short time interval (3-8 
sessions). This differs from conventional external beam radiation therapy, where a typical 
treatment course can last anywhere from 10 to 30 sessions. The smaller number of treatment 
session associated with SBRT may have unique biological effect on the tumor vasculature not 
found in the conventional form of radiation therapy. 
 
Measuring change in perfusion after therapy may be used to assess the success of therapy. 
Assessment of RT is traditionally accomplished using change in tumor morphology, using the 
RECIST criteria [16]. However, this tumor volume change does not necessarily describe change 
in tumor physiology. In addition, large necrotic regions of tissue may be included in the 
morphological quantification[18]. The utilization of DCE-CT for outcome assessment in RT has 

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been previously studied in several cancer sites, including the liver [1,3-5]. However, no study, to 
the best of our knowledge, has attempted to use DCE-CT as an outcome assessment tool for SBRT 
treatment of liver cancer. This study aims to determine if perfusion changes from SBRT of liver 
cancer may be used for outcome assessment and prediction of prognosis. 
 
Quantification of tumor perfusion has been accomplished in several modalities including MRI and 
CT [6,7]. Recent advances in scanner and image quality has made CT a viable modality for the 
quantification of perfusion in Oncology. Some of the advantages of measuring perfusion with CT 
instead of MRI include, but are not limited to: increased spatial resolution, decreased scan time, 
and study and scanner cost.    
Summary:  
Previous studies in other cancer sites have shown DCE-CT is suitable for use in human subjects. 
In addition, these studies have shown DCE-CT provides useful information for outcome 
assessment of radiation therapy. No work has studied DCE-CT for outcome assessment of SBRT 
treatment of liver malignancies. The preliminary results of our work shows that the DCE-CT 
imaging protocol has been optimized, and is suitable for patient use.  
 
2.3 
POTENTIAL RISKS AND BENEFITS 
 
2.3.1 KNOWN POTENTIAL RISKS  
 
Study participants will receive contrast enhanced CT scans. Adverse reactions following the use 
of CT contrast are usually mild to moderate, self-limited, and transient. In clinical studies, CT 
contrast was associated with the following adverse reactions at a frequency greater than 1%: pain 
(2.8%), burning sensation (1.4%), nausea (1.2 %), hot flashes (1.5%), and warmth (1.1%). Less 
well defined but perhaps more important is the risk of contrast-induced nephropathy, which has 
incidence of 2% in general population but can have high (~30%) incidence in patients with chronic 
renal impairment. 
 
Patients who participate in this study will also receive slightly higher doses of ionizing radiation 
than those who do not, due to the extra imaging scans; on the order of 5 mGy to tissues of the 
abdomen. Patients will go on to receive SBRT for liver malignancies, which forms the primary 
component of the normal ionizing radiation dose in this population. This treatment delivers an 
average of roughly 10 Gy to normal tissue; the additional imaging represents a 0.05% increase in 
overall ionizing radiation dose from radiotherapy related procedures. We expect the additional 
DCE-CT scans will result in no additional adverse events (AEs).  
 

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2.3.2 KNOWN POTENTIAL BENEFITS  
 
The goal of this study is to determine if perfusion, as measured from DCE-CT, can be imaged in 
the liver to assess treatment response from radiation therapy. This may provide unique 
physiological information that will improve outcome assessment, as well as predict treatment 
efficacy, for patients treated with SBRT for liver cancer. Specifically, this study investigates if 
perfusion characteristics, as well as their respective changes from pre-treatment to post-treatment 
DCE-CT imaging, may have a relationship with prognosis. This will potentially provide a strong 
measure of treatment prognosis that will provide the physician with crucial information that may 
guide follow-up treatments if prognosis is predicted to be poor.  
 
Additionally, this study will provide preliminary data that will help design a future investigation 
into the predictive performance of perfusion at pre-treatment and intra-treatment. The ability of 
pre-treatment perfusion characteristics to predict response will be examined. This is potentially a 
powerful tool to predict patient-specific response before treatment begins. It may be possible to 
customize treatment planning based on pre-treatment perfusion characteristics.  
 
The risks to participants are reasonable in relation to the anticipated benefits to participants and/or 
society, and in relation to the importance of the knowledge that may reasonably be expected to 
result, thereby falling in favor of performing the study: 
 
• Justify the importance of the knowledge gained: This study protocol proposes a 
prospective, rigorous, and safe study to provide preliminary data to assess the utility of 
DCE-CT liver imaging in radiation oncology. 
 
3 
OBJECTIVES AND PURPOSE 
Primary Objective: Investigate the association between the delivered radiation therapy dose 
distribution and the change in perfusion measurement following treatment. 
 
The goal of this study is to determine if perfusion, as measured from DCE-CT, can be imaged in 
the liver to assess treatment response from radiation therapy. Total therapeutic radiation dose 
delivered during SBRT will be used as a surrogate measurement for treatment response. This may 
provide unique physiological information that will improve outcome assessment, as well as predict 
treatment efficacy, for patients treated with SBRT for liver cancer.  
 
Specifically, this study investigates if perfusion characteristics, as well as their respective changes 
from pre-treatment to post-treatment DCE-CT imaging, may have a relationship with therapeutic 
radiation dose. This will potentially provide a strong measure of treatment prognosis that will 

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provide the physician with crucial information that may guide follow-up treatments if prognosis is 
predicted to be poor. Additionally, we will be able to assess if DCE-CT imaging parameters 
changes after liver SBRT treatment are reproducible and relative to normal liver function. 
 
Secondary Objective: Explore any demographic differences in perfusion metrics. 
 
The secondary objective will be used to provide descriptive information on demographic 
differences in perfusion metrics. Should a larger study be warranted this information will be crucial 
in study design and analysis to control for demographic differences.  
 
4 
STUDY DESIGN AND ENDPOINTS 
4.1 
DESCRIPTION OF THE STUDY DESIGN 
This is a pilot study designed to evaluate the feasibility of DCE-CT imaging for outcome 
assessment of radiation therapy for the treatment of liver cancer. Because this is a pilot study, no 
clinical decisions or interventions will deviate from standard of care.  
 
Pre-treatment perfusion assessment will be performed before the start of SBRT. The first Post-
treatment perfusion assessment will be within six hours after the end of the first fraction of SBRT. 
The final Post-treatment perfusion assessment will be six weeks after the end of SBRT (with an 
allowed time window of 4-8 weeks). 
 
Step 1 (Enrollment & Screening): 
 
Patients with liver cancer receiving stereotactic body radiation (SBRT) as part of their standard of 
care will be eligible for study enrollment. SBRT is similar to conventional, photon-based radiation 
therapy. SBRT differs from conventional radiation therapy by utilizing less treatment sessions, 
also call ‘a fraction’, and a higher radiation dose per treatment session. Typically, SBRT is 5 
fractions, whereas conventional radiation therapy may have 10 to 30 fractions, depending on the 
total prescribed radiation dose. DCE-CT imaging will be added at three specific time points of the 
clinical workflow for the quantification of perfusion.  
 
Step 2 (Pre-treatment perfusion assessment): 
 
Subjects will have DCE-CT imaging before the initiation of radiation therapy. Under SOC, all 
patients receiving radiation therapy undergo a planning CT simulation session. This session of CT 
imaging produces the CT study that will be used to create the radiation treatment plan. Under this 

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study, an additional DCE-CT scan will be acquired to quantify a patient’s baseline perfusion 
characteristics.  
 
Step 3 (Initiation of Radiation Therapy and Post-treatment perfusion assessment): 
 
Subjects will begin radiation therapy for treatment of liver cancer or metastases. Each individual 
treatment session, also known as a “fraction”, will utilize on-board imaging to ensure localization 
of treatment to the patient’s unique anatomy for each session. This is the SOC with no 
modifications to the radiation treatment characteristics. Subjects will have DCE-CT imaging 
within six hours of receiving the first fraction of radiation therapy to assess the SBRT related 
changed to baseline perfusion characteristics. 
 
Step 4 (Completion of Radiation Therapy): 
 
Subjects will complete radiation therapy in 1 to 2 weeks, depending on prescribed radiation dose. 
This is the SOC with no modifications to the radiation treatment characteristics. 
 
Step 5 (Six-week follow-up/Post-treatment perfusion assessment): 
 
Subjects will have a follow-up visit with the radiation oncologist approximately 6 weeks after the 
completion of radiation therapy. DCE-CT imaging will be performed at this time to assess 
perfusion. This perfusion measure will be for outcome assessment of radiation effects. This DCE-
CT imaging will be for research purposes. 
 
4.2 
STUDY ENDPOINTS 
 
4.2.1 PRIMARY ENDPOINTS 
 
Primary endpoints include total therapeutic radiation dose delivered and DCE-CT profusion 
metrics at baseline, following first treatment, and 6 weeks after treatment. Profusion metrics 
include: KTrans (aka extraction-flow product), blood volume, and blood flow. 
 
 
4.2.2 SECONDARY ENDPOINT 
 
Patient demographic data will be combined with the primary endpoints to assess whether perfusion 
metrics differ depending on baseline demographics. 
 
Demographic information (e.g., sex, age, race, etc.) will be combined with primary profusion 
endpoints. 

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5 
STUDY ENROLLMENT AND WITHDRAWAL 
5.1 
PARTICIPANT INCLUSION CRITERIA 
In order to be eligible to participate in this study, an individual must meet all of the following 
criteria: 
1. Provision to sign and date the consent form 
2. Stated willingness to comply with all study procedures and be available for the duration of 
the study 
3. Be a Male or Female aged 18-100 
4. Diagnosed with Liver HCC or metastases 
5. Must be receiving or will plan to receive SBRT for Liver HCC or metastases  
 
5.2 
PARTICIPANT EXCLUSION CRITERIA 
An individual who meets any of the following criteria will be excluded from participation in this 
study: 
1. Allergy to iodine contrast  
2. CT with contrast not offered as a Standard of Care 
3. Pregnant women 
 
5.3 
STRATEGIES FOR RECRUITMENT AND RETENTION 
This study will be open to all patients meeting eligibility criteria seen at the University of Colorado 
Cancer Center main campus in Aurora, CO.  
 
Target sample size is 10 patients. In total, the Department of Radiation Oncology treats 
approximately 50 liver cancer patients with SBRT per year. Assuming an enrollment rate of 40% 
and a dropout rate of 25%, a conservative estimate is enrolling 10 patients in 12 months.  
 
5.4 
PARTICIPANT WITHDRAWAL OR TERMINATION 
5.4.1 REASONS FOR WITHDRAWAL OR TERMINATION 
 
Participants are free to withdraw from participation in the study at any time upon request. Study 
subjects may be prematurely terminated from the study for the following reasons: 
• 
Physician, PI, and/or patient decides to discontinue radiation treatment 
• 
Noncompliance with the study protocol 

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• 
Development of unrelated illness which compromises study participation 
• 
The subject withdraws consent (no further data collection or submission will be expected) 
Subjects may stop study participation for any reason without jeopardizing their relationship with 
the healthcare providers. 
 
5.4.2 HANDLING OF PARTICIPANT WITHDRAWALS OR TERMINATION 
Because this is a pilot study, where no clinical decisions will be made based on the DCE-CT, no 
effort will be made to follow withdrawn study participants or study participants that have 
completed the study.  
 
5.5 
PREMATURE TERMINATION OR SUSPENSION OF STUDY (STUDY STOPPING 
RULES) 
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to the Lead PI (Moyed 
Miften). If the study is prematurely terminated or suspended, the PI will promptly inform the IRB 
and will provide the reason(s) for the termination or suspension. 
 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• Determination of unexpected, significant, or unacceptable risk to participants. 
• Insufficient compliance to protocol requirements. 
• Data that are not sufficiently complete and/ or evaluable. 
• Determination of futility. 
 
Study may resume once concerns about safety, protocol compliance, and data quality are addressed 
and satisfy the sponsor, IRB and DSMC. 
 
6 
STUDY AGENT 
6.1 
STUDY AGENT(S) AND CONTROL DESCRIPTION 
As described above, DCE-CT will be utilized to correlate perfusion imaging tumor changes with 
local control and normal tissue perfusion changes with normal tissue toxicities. All patients will 
undergo DCE-CT performed at the time of CT simulation, after the first fraction of SBRT, and 6 
weeks after completion of SBRT (see schema). The DCE-CT scan performed at the time of CT 
simulation and subsequent scans will be performed in treatment position (which will be defined 
on an individual patient basis by the treating radiation oncologist). DCE-CT will be performed on 

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the Siemens AS open scanner within the University of Colorado Department of Radiation 
Oncology. Iodine contrast agent (50-100 mL) will be injected, per standard of care, at 3 mL per 
second and axial images centered at the tumor will be acquired. 
 
7 
STUDY PROCEDURES AND SCHEDULE 
7.1 
STUDY PROCEDURES/EVALUATIONS 
1. Subject enrollment and initial visit with radiation oncologist  
 
The subject will have a pre-treatment, standard of care work-up visit with the radiation oncologist. 
During this visit, the study team will explain the study to the patient and obtain informed consent. 
After consent has been obtained, the study team will assess if the subject meets study criteria and 
can be enrolled into the study.  
 
2. Pre-treatment DCE-CT Imaging 
 
During the initial CT simulation process, the pre-treatment perfusion imaging will be obtained 
using DCE-CT. The initial CT simulation process is used to create the radiation therapy treatment 
plan and is a part of SOC. At the end of the CT simulation session, additional DCE-CT imaging 
will be acquired. 
 
3. Delivery of Radiation Therapy 
 
Treatment will be performed on a linear accelerator with on-board imaging capabilities to align 
the subject to the same treatment position for every treatment session. Throughout treatment, the 
subject will have a weekly evaluation with the radiation oncologist to help manage any health 
problems that may arise. 
 
Subjects will have DCE-CT imaging within six hours of receiving the first fraction of radiation 
therapy to assess the SBRT related changed to baseline perfusion characteristics. 
 
 
 
 
 
4. Six week follow-up visit/Post-treatment DCE-CT Imaging  
 
The subject will have a SOC six week follow-up visit with the radiation oncologist. During the 
consult, the radiation oncologist will assess any issues arising from radiation treatment. At this 

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consult, the subject will also undergo their final session of DCE-CT imaging to assess perfusion 
changes after completion of radiation therapy.  
 
7.2 
STUDY SCHEDULE 
 
7.2.1 SCREENING 
 
The screening process will be begin once a patient is referred to radiation oncology for radiation 
therapy for the treatment of liver cancer. The patient will undergo a standard consultation with a 
radiation oncologist. The patient will be explained the risks and benefits of participation in the 
study. The patient will also be explained the study is completely voluntary. Patients will be 
informed of the study, explained the study purpose and asked to provide informed consent. 
 
7.2.2 ENROLLMENT/BASELINE 
• Verify inclusion/ exclusion criteria. 
• Obtain Demographic information. 
• Baseline clinical information (drinking status, medications, medical treatments including 
cancer treatments, cancer history) 
• Obtain urine pregnancy test in women of childbearing potential.  
• CT simulation for radiotherapy planning 
• DCE-CT (performed at the time of CT simulation) 
 
7.2.3 FOLLOW-UP  
 
• Subjects will have DCE-CT imaging within six hours of receiving the first fraction of 
radiation therapy to assess the SBRT related changed to baseline perfusion characteristics 
• DCE-CT imaging will be made at 6 weeks (+/- 1 week) after completion of SBRT. 
• Record adverse events as reported by participant or observed by investigator if related to 
DCE-CT. 
• Record participant’s adherence to treatment program. 
 
 
 
 
7.2.4 FINAL STUDY VISIT 
• Record adverse events as reported by participant or observed by investigator if related to 
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• Record participant’s adherence to treatment program. 
 
7.2.5 EARLY TERMINATION VISIT 
No procedures will be performed. 
7.2.6 UNSCHEDULED VISIT 
No procedures will be performed. 
 
 
 
 
 
 
 
 
 
 
 
 
 
7.2.7 SCHEDULE OF EVENTS TABLE 
 
Study Visits 
 
Screening 
Baseline 
Visit 
Mid-
Treatment 
 
6 weeks 
Follow-up 
Visit Window 
-28 Days to Day 0 
Day 0- Prior to 
Treatment 
Between 1st and 
last treatment 
fractions 
 
4-6 weeks post-
treatment 
Procedures 
 
 
Visit with Radiation 
Oncologist 
X 
X 
X 
 
X 
Informed Consent 
X 
 
 
 
 
DCE-CT imaging 
 
X (R) 
X (R) 
 
X (R)  
Adverse Events 
 
X 
X 
 
X 
 

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Study Event 
Suggested timeline 
Procedure 
SOC or Research 
Screening 
At time of initial consult 
with Radiation Oncology 
Consultation with Radiation 
Oncologist 
SOC 
Patient signs consent form 
Research 
Pre-Treatment DCE-CT 
imaging  
Within 3 weeks prior to the 
initiation of radiation 
therapy 
CT imaging for treatment 
planning 
SOC 
DCE-CT imaging 
Research 
Delivery of Radiation 
Therapy  
1-2 Weeks 
Delivery of Radiation 
treatment of liver cancer 
SOC 
 
 
 
 
6 week follow-up visit 
4-6 weeks after completion 
of radiation therapy 
Appointment with radiation 
oncologist 
SOC 
DCE-CT imaging 
Research 
 
   
7.4 
PROHIBITED MEDICATIONS, TREATMENTS, AND PROCEDURES  
There are no restrictions on concomitant medications, treatments (i.e. chemotherapy, hormonal, 
immunotherapy) and procedures while on study. 
 
8 
ASSESSMENT OF SAFETY 
8.1 
SPECIFICATION OF SAFETY PARAMETERS 
 
8.1.1 DEFINITION OF ADVERSE EVENTS (AE) 
Adverse event means any untoward medical occurrence associated with the use of an intervention 
in humans. 
Because this is an imaging study, where no clinical decision will be altered, we will only record 
AEs that have to do with the research procedures. The three research procedures are the pre-
treatment, post-first fraction, and post-treatment DCE-CT imaging. 
 
8.1.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE) 
Serious adverse event or serious suspected adverse reaction. An AE or suspected adverse 
reaction is considered “serious” if, in the view of either the investigator or sponsor, it results in 

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any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or 
prolongation of existing hospitalization, a persistent or significant incapacity or substantial 
disruption of the ability to conduct normal life functions, or a congenital anomaly/ birth defect. 
Important medical events that may not result in death, be life-threatening, or require hospitalization 
may be considered serious when, based upon appropriate medical judgment, they may jeopardize 
the patient or subject and may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition. Examples of such medical events include allergic bronchospasm 
requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions 
that do not result in inpatient hospitalization, or the development of drug dependency or drug 
abuse.  
 
Because this is an imaging study, where no clinical decision will be altered, we will only record 
SAEs that have to do with the research procedures. The three research procedures are the pre-
treatment, post-first fraction and post-treatment DCE-CT imaging. 
 
8.1.3 DEFINITION OF UNANTICIPATED PROBLEMS (UAP) 
 
This study will use the COMIRB definition of UAP. An unanticipated problem is any event or 
information that was unforeseen and indicates that the research procedures caused harm (including 
physical, psychological, economic, or social harm) to participants or others or indicates that 
participants or others are at increased risk of harm than was previously known or recognized.  
   
8.2 
CLASSIFICATION OF AN ADVERSE EVENT 
 
8.2.1 SEVERITY OF EVENT 
For AEs not included in the protocol-defined grading system, the following guidelines will be used 
to describe severity. 
• Mild – Events require minimal or no treatment and do not interfere with the 
participant’s daily activities. 
• Moderate – Events result in a low level of inconvenience or concern with the 
therapeutic measures. Moderate events may cause some interference with functioning. 
• Severe – Events interrupt a participant’s usual daily activity and may require systemic 
drug therapy or other treatment. Severe events are usually potentially life-threatening 
or incapacitating. 
  
8.2.2 RELATIONSHIP TO STUDY INTERVENTION 

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Because this is an imaging study, where no clinical decision will be altered, we will only record 
AEs that have to do with the research procedures. The three research procedures are the pre-
treatment, post-first fraction and post-treatment DCE-CT imaging. 
 
8.2.3 EXPECTED ADVERSE EVENTS  
The Investigator will be responsible for determining whether an SAE is expected or unexpected. 
An SAE will be considered unexpected if the nature, severity, or frequency of the event is not 
consistent with the risk information previously described for the study agent. 
 
8.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
The occurrence of an AE or SAE may come to the attention of study personnel during study visits 
and interviews of a study participant presenting for medical care, or upon review by a study 
monitor. All AEs including local and systemic reactions not meeting the criteria for SAEs will be 
captured on the appropriate CRF. Information to be collected includes event description, time of 
onset, clinician’s assessment of severity, relationship to study product (assessed only by those with 
the training and authority to make a diagnosis), and time of resolution/ stabilization of the event. 
All AEs occurring while on study must be documented appropriately. All AEs will be followed to 
adequate resolution. 
 
The PI will record all reportable events with start dates occurring any time after informed consent 
is obtained until the last study visit. At each study visit, the investigator will inquire about the 
occurrence of AE/ SAEs since the last visit. Events will be followed for outcome information until 
resolution or stabilization. 
 
8.4 
REPORTING PROCEDURES 
8.4.1 ADVERSE EVENT REPORTING  
 
Reporting of UAPs, SAEs, and reportable AEs will be performed pursuant to the UCCC DSMC 
and IRB institutional policy. 
 
8.4.2 SERIOUS ADVERSE EVENT REPORTING  
 
All SAEs will be followed until satisfactory resolution or until the PI deems the event to be chronic 
or the adherence to be stable.  
 
SAEs will be reported pursuant to section 8.6.  
  

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8.4.3 UNANTICIPATED PROBLEM REPORTING  
 
This study will follow COMIRB’s guidance for UAP reporting and the DSMC’s requirements 
(discussed in section 8.6). AEs, noncompliance and protocol violations will be recorded and 
reported as required either promptly (within 5 days of Sponsor-Investigator’s knowledge) or at the 
time of the study’s continuing review.  
 
It is the responsibility of the PI to report incidents or events that meet the criteria for UAPs 
reporting to their IRB using the IRB’s standard UAP form. The PI is responsible for reporting 
the UAP to the UCCC DSMC, if applicable.   
 
8.5 
STUDY HALTING RULES  
Administration of a study intervention will be halted when three grade 3 AEs related to DCE-CT 
that are determined to be at least “probably related” are reported to the clinician. The clinician will 
notify the study sponsor and PIs immediately when the third grade 3 event is reported and 
enrollment screens will stop accepting new study participants. The study sponsor will inform the 
UCCC DSMC members within 24 hours of this occurrence and will provide the UCCC DSMC 
with AE listing reports. The UCCC DSMC will convene an ad hoc meeting by teleconference or 
in writing as soon as possible. The DSMB will provide recommendations for proceeding with the 
study to the study sponsor. The study sponsor will inform the FDA of the temporary halt and the 
disposition of the study, if applicable. 
 
8.6 
SAFETY OVERSIGHT 
Monitoring and Oversight 
The sponsor investigator will be responsible for monitoring the trial per the trial monitoring plan, 
in addition to overseeing the safety and efficacy of the trial including any specimens collected, 
executing the data and safety monitoring (DSM) plan, and complying with all reporting 
requirements to local and federal authorities. This oversight will be accomplished through 
additional oversight from the Data and Safety Monitoring Committee (DSMC) at the University 
of Colorado Cancer Center (CU Cancer Center).  The DSMC is responsible for ensuring data 
quality and study participant safety for all clinical studies at the CU Cancer Center, which is the 
coordinating institution of this trial.   A summary of the DSMC’s activities is as follows: 
• Conduct of internal audits 
• Ongoing review of all serious adverse events (SAEs), unanticipated problems (UAPs) and 
reportable adverse events (AEs) 
• Has the authority to close and/or suspend trials for safety or trial conduct issues 

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• May submit recommendations for corrective actions to the CU Cancer Center’s Executive 
Committee 
Per the CU Cancer Center Institutional DSM Plan, SAEs, UAPs and reportable AEs are reported 
to the DSMC, IRB and the sponsor investigator per protocol.  All SAEs, UAPs and reportable AEs 
are to be reported to the DSMC within 5 business days of the sponsor investigator receiving 
notification of the occurrence. 
Study audits conducted by the DSMC will consist of review of the regulatory records, consent 
forms and source data verification.  Documentation of the audit conducted by the DSMC will then 
need to be submitted to the IRB of record at the time of the IRB’s continuing review of this trial. 
 
9 
CLINICAL MONITORING 
Clinical site monitoring will be conducted to ensure that the rights and well-being of human 
participants are protected, that the reported trial data are accurate, complete, and verifiable, and 
that the conduct of the trial is in compliance with the currently approved protocol/ amendment(s), 
with GCP, and with applicable regulatory requirement(s).  
 
Monitoring for this study will be performed by a CU Cancer Center Clinical Monitor in accordance 
with the clinical monitoring plan (CMP), incorporated herein by reference. The CMP describes in 
detail who will conduct the monitoring, at what frequency monitoring will be done, at what level 
of detail monitoring will be performed, and the distribution of the monitoring reports. 
 
Independent audits will be conducted by the CU Cancer Center DSMC to ensure monitoring 
practices are performed consistently across all participating sites, if applicable, and that monitors 
are following the CMP. 
 
10 
STATISTICAL CONSIDERATIONS  
10.1 STATISTICAL AND ANALYTICAL PLANS 
The utility of perfusion falls under two categories: predictive performance from DCE-CT imaging 
changes, and outcome assessment of radiation therapy treatment. Perfusion will characterized for 
a number of different parameters from a pharmacokinetic model. Multiple pharmacokinetic 
models can describe perfusion. For completeness, we will examine several models including: 
tissue homogeneity, Tofts, extended Tofts, and Patlak. Model goodness of fit will be assessed with 
root mean square error. The following perfusion parameters, derived from previously mentioned 

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pharmacokinetic models, will be quantified for each DCE-CT session: blood flow, blood volume 
of vascular space, blood volume of extracellular space, and intra-compartment plasma flow. For 
each model, these perfusion parameters will have the mean, extremums, and standard deviation of 
each parameter value calculated. 
 
Treatment response will be assessed using the DCE-CT imaging changes from the baseline to the 
6-week follow-up. Changes in perfusion parameters will be compared to the delivered dose with 
correlation coefficients, logistic regression analysis, and receiver operating characteristic analysis.   
 
10.2 STATISTICAL HYPOTHESES 
• Primary Efficacy Endpoint(s): 
No formal hypothesis testing will be conducted for the primary analysis 
 
10.3 ANALYSIS DATASETS 
All participants who completed their baseline DCE-CT scan, had at least one radiation therapy 
treatment and one follow-up DCE-CT scan will be included in the analysis dataset to assess change 
in perfusion measurements from baseline to first follow-up. The analysis dataset for change in 
perfusion metrics at 6 weeks will include participants who completed their radiation treatment and 
have both baseline and 6-week DCE-CT scans. 
  
10.4 DESCRIPTION OF STATISTICAL METHODS 
10.4.1 
GENERAL APPROACH 
 
 
How profusion metrics change following SBRT treatment is unknown. Therefore, this is a 
prospective, pilot study is primarily aimed at gathering preliminary data on profusion metrics and 
assessing the relationship between change in profusion and radiation dose delivered from SBRT. 
Due to the limited knowledge on how radiation therapy will affect profusion metrics, change in 
profusion metrics following therapy will be assessed both after a patient’s first treatment and at 6-
weeks following their end of the SBRT treatment. Descriptive statistics will be provided for all 
measured variables. 
 
10.4.2 
ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT(S) 
The primary endpoint of this study is change in profusion metrics from baseline to end of first 
radiation treatment and 6-weeks after treatment has ended. Additionally, total radiation dose 
delivered from SBRT will be captured and used as a surrogate measurement for treatment 
response.  

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Individual profusion metrics will be plotted as well as means with corresponding standard errors 
for the three time points. Change in profusion metrics from baseline versus radiation dose received 
will be plotted separately for the two follow-up DCE-CT scans. Correlation between change in 
profusion and total radiation dose received will be evaluated using Spearman’s correlation 
coefficient.  
 
10.4.3 
ANALYSIS OF THE SECONDARY ENDPOINT(S) 
To assess descriptively whether there are signs that profusion metrics differ based on patient 
demographics the following demographic information will be captured; age , sex, race, clinical 
stage at diagnosis. Change in profusion metrics from baseline to each of the two follow-up DCE-
CT scans will be stratified by demographic information and descriptive statistics will be presented, 
e.g., sample size, mean, median, standard deviation, and range. 
 
10.4.4 
SAFETY ANALYSES 
Should an AE related to the study intervention (i.e., additional DCE-CT scans) occur, the study 
will be terminated. Definition and monitoring of AEs are detailed in section 8. 
10.4.5 
ADHERENCE AND RETENTION ANALYSES 
There are no pre-planned adherence and retention analyses. 
 
10.4.6  
BASELINE DESCRIPTIVE STATISTICS 
Baseline descriptive statistics for patient demographics will be collected and reported.  
 
10.4.7 
PLANNED INTERIM ANALYSES  
There are no planned interim analyses. 
  
10.5 SAMPLE SIZE 
The study will enroll a minimum of 10 patients with a maximum enrollment of 15 patients to allow 
for screen failures and dropouts. This sample size was based the number of patients that would be 
reasonable for the Department of Radiation Oncology to recruit within a year. The Department of 
Radiation Oncology treats approximately 50 liver cancer patients with SBRT per year. Assuming 
an enrollment rate of 40% and a dropout rate of 25%, a conservative estimate is enrolling a 
maximum of 15 patients in 12 months. 
 

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11 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS 
To protect confidentiality of participants, medical and research records for this trial will be 
maintained in compliance with regulatory and institutional requirements.  
 
The following data will be collected on electronic-based Case Report Forms (eCRFs): 
• Demographic information (age, sex, race) 
• Baseline clinical information (drinking status, medications, medical treatments including 
cancer treatments, cancer history) 
• Results of study procedures as detailed in protocol 
 
 
Only the following people will have access to data and documents collected on CRFs: 
• Study investigators and research staff participating in this study 
 
Our site will permit authorized representatives of the UCCC and regulatory agencies to examine 
clinical records for quality assurance reviews, audits, and valuation of study safety, progress, and 
data validity. In additional to study monitors, study personnel on the study roster will have access 
to the study data. 
 
Should study participants withdraw their consent from the study, no further data will be collected 
on them for this study.  
 
Source data and documents will be kept according to HIPAA guidelines.  
 
12 
QUALITY ASSURANCE AND QUALITY CONTROL 
Quality Control (QC) procedures will be implemented beginning with the data entry system and 
data QC checks that will be run on the database will be generated. Any missing data or data 
anomalies will be communicated to the site(s) for clarification/ resolution. 
 
Following written SOPs, the study monitor will verify that the clinical trial is conducted and data 
are generated, documented (recorded), and reported in compliance with the protocol, GCP, and the 
applicable regulatory requirements (e.g., Good Laboratory Practices (GLP), Good Manufacturing 
Practices (GMP)). 
 
The investigational site will provide direct access to all trial-related sites, source data/ documents, 
and reports for the purpose of monitoring and auditing by the DSMC audit team, and inspection 
by local and regulatory authorities. 
 

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13 
ETHICS/PROTECTION OF HUMAN SUBJECTS  
13.1 ETHICAL STANDARD  
The PI will ensure that this study is conducted in full conformity with regulations for the Protection 
of Human Subjects of Research codified in 45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56. ICH 
E6 may also be followed to the extent it has been adopted by and is in accordance with FDA 
regulations. 
 
13.2 INSTITUTIONAL REVIEW BOARD  
The protocol, informed consent form(s), recruitment materials, and all subject materials will be 
submitted to the Colorado Multiple Institutional Review Board (COMIRB) for review and 
approval. Approval of both the protocol and the consent form must be obtained before any subject 
is enrolled. Any amendment to the protocol will require review and approval by COMIRB before 
the changes are implemented to the study. All changes to the consent form will COMIRB 
approved; a determination will be made regarding whether previously consented participants need 
to be re-consented. 
 
13.3 INFORMED CONSENT PROCESS  
Before protocol-specified procedures are carried out, consenting professionals will explain full 
details of the protocol and study procedures as well as the risks involved to participants prior to 
their inclusion in the study. Participants will also be informed that they are free to withdraw from 
the study at any time. All participants must sign an IRB-approved consent form indicating their 
consent to participate. This consent form meets the requirements of the Code of Federal 
Regulations and the Institutional Review Board of this Center. The consent form will include the 
following:  
 
1. The nature and objectives, potential risks and benefits of the intended study.  
2. The length of study and the likely follow-up required.  
3. The name of the investigator(s) responsible for the protocol.  
4. The right of the participant to accept or refuse study interventions/interactions and to withdraw 
from participation at any time.  
 
Before any protocol-specific procedures can be carried out, the consenting professional will fully 
explain the aspects of patient privacy concerning research specific information and participants 
will sign an Informed Consent Form.  
 

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Each participant and consenting professional will sign the consent form. The participant must 
receive a copy of the signed informed consent form. 
 
13.3.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO 
PARTICIPANTS 
Consent forms describing in detail the study agent, study procedures, and risks are given to the 
participant and written documentation of informed consent is required prior to starting 
intervention/ administering study product.  
 
13.3.2 CONSENT PROCEDURES AND DOCUMENTATION 
 
Informed consent process will be initiated prior to the individual’s agreeing to participate in the 
study and continues throughout the individual’s study participation. Extensive discussion of risks 
and possible benefits of participation will be provided to the participants and their families.  
 
Consent forms will be IRB-approved and the participant will be asked to read and review the 
document. The investigator will explain the research study to the participant and answer any 
questions that may arise. All participants will receive a verbal explanation in terms suited to their 
comprehension of the purposes, procedures, and potential risks of the study and of their rights as 
research participants. Participants will have the opportunity to carefully review the written consent 
form and ask questions prior to signing. The participants will have the opportunity to discuss the 
study with their surrogates or think about it prior to agreeing to participate. The participant will 
sign the informed consent document prior to any procedures being done specifically for the study.  
 
The participants may withdraw consent at any time throughout the course of the trial. A copy of 
the informed consent document will be given to the participants for their records. The rights and 
welfare of the participants will be protected by emphasizing to them that the quality of their 
medical care will not be adversely affected if they decline to participate in this study. 
 
The study allows the inclusion of non-English speaking and non-reading participants. Witnesses 
to these consent processes will be individuals not associated with the trial and will not have a 
conflict of interest. 
 
13.4 PARTICIPANT AND DATA CONFIDENTIALITY  
Participant confidentiality is strictly held in trust by the participating PIs, their staff, and the 
sponsor(s) and their agents. This confidentiality is extended to cover testing of biological samples 
and genetic tests in addition to the clinical information relating to participants. Therefore, the study 
protocol, documentation, data, and all other information generated will be held in strict confidence. 

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No information concerning the study or the data will be released to any unauthorized third party 
without prior written approval of the sponsor. 
 
The study monitor, other authorized representatives of the sponsor, representatives of the IRB or 
pharmaceutical company supplying study product may inspect all documents and records required 
to be maintained by the investigator, including but not limited to, medical records (office, clinic, 
or hospital) and pharmacy records for the participants in this study. The clinical study site will 
permit access to such records. 
 
The study participant’s contact information will be securely stored at each clinical site for internal 
use during the study. At the end of the study, all records will continue to be kept in a secure location 
for as long a period as dictated by local IRB and Institutional regulations. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, 
will be transmitted to and stored at the University of Colorado Cancer Center. This will not include 
the participant’s contact or identifying information. Rather, individual participants and their 
research data will be identified by a unique study identification number. The study data entry and 
study management systems used by clinical sites and by the University of Colorado Cancer 
research staff will be secured and password protected. At the end of the study, all study databases 
will be de-identified and archived at the University of Colorado Cancer Center. 
 
14 
DATA HANDLING AND RECORD KEEPING  
14.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the 
site PI. The PI is responsible for ensuring the accuracy, completeness, legibility, and timeliness of 
the data reported.  
 
All source documents should be completed in a neat, legible manner to ensure accurate 
interpretation of data. When making changes or corrections, cross out the original entry with a 
single line, and initial and date the change. DO NOT ERASE, OVERWRITE, OR USE 
CORRECTION FLUID OR TAPE ON THE ORIGINAL. 
 
Copies of the electronic CRF (eCRF) will be provided for use as source documents and maintained 
for recording data for each participant enrolled in the study. Data reported in the eCRF derived 
from source documents should be consistent with the source documents or the discrepancies should 
be explained and captured in a progress note and maintained in the participant’s official electronic 
study record. 

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Clinical data (including AEs, concomitant medications, and expected adverse reactions data) and 
clinical laboratory data will be entered into REDCapTM.  The data system includes password 
protection and internal quality checks, such as automatic range checks, to identify data that appear 
inconsistent, incomplete, or inaccurate. Clinical data will be entered directly from the source 
documents. 
  
14.2 STUDY RECORDS RETENTION  
Study documents should be retained for a minimum of 7 years after the last approval of an 
investigational marketing application and until there are no pending or contemplated marketing 
applications or until at least 7 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 local regulations, or institution policies. No records will be 
destroyed without the written consent of the sponsor, if applicable. It is the responsibility of the 
sponsor to inform the PI when these documents no longer need to be retained.  
 
14.3 PROTOCOL DEVIATIONS  
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or SOP 
requirements. The noncompliance may be either on the part of the participant, the investigator, or 
the study site staff. As a result of deviations, corrective actions are to be developed by the site and 
implemented promptly. These practices are consistent with ICH E6, sections: 
• 4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3. 
• 5.1 Quality Assurance and Quality Control, section 5.1.1. 
• 5.20 Noncompliance, sections 5.20.1 and 5.20.2. 
It is the responsibility of the study team to use continuous vigilance to identify and report 
deviations within 5 working days of identification of the protocol deviation, or within 5 working 
days of the scheduled protocol-required activity. All deviations must be addressed in study source 
documents, reported to CUCC DSMC. Protocol deviations must be sent to the local IRB per their 
guidelines. The site PI/ study staff is responsible for knowing and adhering to their IRB 
requirements. Further details about the handling of protocol deviations will be included in the -
SOP and/or study procedures manual.  
 

PI:   Miften 
Protocol #:   18-2874 
Version Date:  01/16/2020 
 
33 of 34 
 
16 
CONFLICT OF INTEREST POLICY 
Independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical. Any actual conflict of interest of persons who have a role in the design, 
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed.by the 
University of Colorado Denver’s (UCD) Office of Regulatory Compliance Conflict of Interest and 
Commitment Management (COIC) program. Persons with a perceived conflict of interest will have 
such conflicts managed in a way that is appropriate to their participation in the trial. Conflict of 
Interest management plans are project-specific and are reviewed at least annually. UCD has 
integrated the institutional conflict of interest management program with its existing program. 
 
 
17  
LITERATURE REFERENCES  
[1]  
Miller KD, et al. Cancer treatment and survivorship statistics, 2016. CA: a cancer journal for clinicians 
2016;66:271‐289. 
 
[2] 
 Shah SA, et al. Underutilization of therapy for hepatocellular carcinoma in the medicare population. 
Cancer 2011;117:1019‐1026. 
 
[3]  
Xu L, et al. Racial disparities in treatment and survival of patients with hepatocellular carcinoma in the 
United States. Hepatobiliary surgery and nutrition 2016;5:43‐52. 
 
[4]  
Meric‐Bernstam F Mills GB. Overcoming implementation challenges of personalized cancer therapy. 
Nature Reviews Clinical Oncology 2012;9:542. 
 
[5]  
Stillwagon GB, et al. 194 Hepatocellular cancers treated by radiation and chemotherapy combinations: 
toxicity and response: A radiation therapy oncology group study. International Journal of Radiation 
Oncology*Biology*Physics 1989;17:1223‐1229. 
 
[6]  
Leibel SA, et al. A comparison of misonidazole sensitized radiation therapy to radiation therapy alone for 
the palliation of hepatic metastases: results of a Radiation Therapy Oncology Group randomized 
prospective trial. International journal of radiation oncology, biology, physics 1987;13:1057‐1064. 
 
[7]  
Russell AH, et al. Accelerated hyperfractionated hepatic irradiation in the management of patients with 
liver metastases: results of the RTOG dose escalating protocol. International journal of radiation 
oncology,biology, physics 1993;27:117‐123. 
 
[8]  
Seo YS, et al. Radiotherapy for 65 patients with advanced unresectable hepatocellular carcinoma. World 
journal of gastroenterology 2008;14:2394‐2400. 
 
[9]  
Seong J, et al. Clinical results and prognostic factors in radiotherapy for unresectable hepatocellular 
carcinoma: a retrospective study of 158 patients. International Journal of Radiation Oncology • Biology • 
Physics 2003;55:329‐336. 
 

PI:   Miften 
Protocol #:   18-2874 
Version Date:  01/16/2020 
 
34 of 34 
 
[10] 
 Robertson JM, et al. The treatment of colorectal liver metastases with conformal radiation therapy and 
regional chemotherapy. International journal of radiation oncology, biology, physics 1995;32:445‐450. 
 
 [11]  
Dawson LA, et al. Escalated focal liver radiation and concurrent hepatic artery fluorodeoxyuridine for 
unresectable intrahepatic malignancies. Journal of clinical oncology : official journal of the American 
Society of Clinical Oncology 2000;18:2210‐2218. 
 
[12]  
Ben‐Josef E, et al. Phase II trial of high‐dose conformal radiation therapy with concurrent hepatic artery 
floxuridine for unresectable intrahepatic malignancies. Journal of clinical oncology : official journal of the 
American Society of Clinical Oncology 2005;23:8739‐8747. 
 
[13]  
Park HJ, et al. Radiation‐Induced Vascular Damage in Tumors: Implications of Vascular Damage in Ablative 
Hypofractionated Radiotherapy (SBRT and SRS). Radiation Research 2012;177:311‐327. 
 
[14]  
McCammon R, et al. Observation of a dose‐control relationship for lung and liver tumors after stereotactic 
body radiation therapy. International journal of radiation oncology, biology, physics 2009;73:112‐118. 
 
[15]  
Eisenhauer EA, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 
1.1). European journal of cancer (Oxford, England : 1990) 2009;45:228‐247. 
 
[16]  
Prezzi D, Khan A Goh V. Perfusion CT imaging of treatment response in oncology. Eur J Radiol 
2015;84:2380‐2385. 
 
 
[17]  
Kierkels RG, et al. Comparison between perfusion computed tomography and dynamic contrast‐enhanced 
magnetic resonance imaging in rectal cancer. International journal of radiation oncology, biology, physics 
2010;77:400‐408. 
 
[18]  
Cuenod CA Balvay D. Perfusion and vascular permeability: basic concepts and measurement in DCE‐CT 
and DCE‐MRI. Diagn Interv Imaging 2013;94:1187‐1204. 
 
18  
APPENDICES  
 
Version 
Date 
Significant Revisions  
 
 
 
 
 
 

Consent and Authorization Form
Combined Biomedical Consent and Separate Main and Optional HIPAA authorizations
CF-151.S, Effective 10-17-18
Page 1 of 11
Principal Investigator:
Moyed Miften, PhD
COMIRB No:
18-2874
Version Date:
01/16/2020
Study Title:
Pilot Study of Dynamic Contrast Enhanced Computed 
Tomography (DCE-CT) Imaging for the assessment of radiation 
therapy outcome for liver cancer patients
Key Information 
________________________________________________________________________
Please read all the information below and ask questions about anything you don’t 
understand before deciding of you want to take part. 
You are being asked to be in a research study. Participation is voluntary. 
Purpose of the study: We are doing this study to learn more about how Dynamic 
Contrast Enhanced Computed Tomography (DCE-CT) can be used to assess how an 
individual’s liver cancer responds to standard radiation treatment.
Procedures: If you agree to participate, the following will happen: 

You will have a screening visit to make sure you are eligible to be in the study. 

If you are eligible, you will have a DCE-CT Scan of your liver before, during, and 
after standard radiation treatment (total of 3 scans).

You will be in the study for approximately 3 months. 
Risks: Participation in research involves risks, including the following: 

The risk of CT scans includes exposure to radiation. A special dye (contrast 
material) will be given to you before the scan. Although rare, the contrast material 
may cause an allergic reaction. The contrast material may cause kidney damage.
Benefits: There is no guarantee that your health will improve if you join this study. This 
study may lead to information that could help patients and health care providers in the 
future. 
COMIRB
APPROVED
For Use
13-Feb-2020
16-Apr-2020

Consent and Authorization Form
COMIRB 18-2874
PI: Miften
Version Date: 01/16/2020
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Alternatives: You can receive standard radiation treatment without participating in this 
study. Please discuss standard treatment and care options with your doctor. 
Detailed Consent 
You are being asked to be in a research study. This form provides you with information 
about the study. A member of the research team will describe this study to you and answer 
all of your questions. Please read the information below and ask questions about anything 
you don’t understand before deciding whether or not to take part. 
Why is this study being done?
This study plans to learn more about if an imaging method known as Dynamic Contrast 
Enhanced Computed Tomography (DCE-CT) can help doctors assess liver cancer and 
metastases.
You are being asked to be in this research study because you have been diagnosed with 
liver cancer or metastases and are currently (or will be) on the standard of care radiation 
treatment known as Stereotactic Body Radiation Therapy (SBRT).
Other people in this study
Up to 15 people from your area will participate in the study. 
Up to 15 people around the country will be in the study. 
What happens if I join this study?
If you join the study, you will be asked to sign this consent form. You will be given a copy 
to keep and the original will be kept at the clinic. You can withdraw from the study at any 
time and without giving a reason. This will not affect the standard medical care you will 
receive.
You will undergo standard computed tomography (CT) imaging for radiation therapy 
planning. This is often called “CT simulation.” The CT image will be used to determine 

Consent and Authorization Form
COMIRB 18-2874
PI: Miften
Version Date: 01/16/2020
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Combined Biomed ICF and Compound HIPAA (CF-151.C, Effective 9-29-15)
which portion of your liver may be functioning well and which portions are not. This will 
help your radiation oncology team better understand how radiation effects liver function.
In addition to receiving the standard of care radiation treatment for your liver cancer or 
metastases, three DCE-CT imaging sessions will be performed.
The next section is an overview of the procedures that will be done and what will be 
expected of you if you participate in this study.
Study Procedures
Below are the study procedures that will take place. 

Informed Consent (Research)
This informed consent form will be discussed with you and you will given a copy of 
this document. If you join the study, you will be asked to sign this consent form 
before you receive any study related tests or procedures.

Dynamic Contrast Enhanced Computed Tomography (DCE-CT) Imaging 
(Research)
This form of computed tomography imaging allows doctors to inject a contrast agent 
and collect images in the area of interest. This information may be able to assess 
your liver cancer or metastases by looking at the tumor as well as the surrounding 
tissue and obtaining information that is unique to you.
Study Visits
Below is a list of when the study procedures will take place. 
1. Screening 
You will learn about the study and provide your consent if you wish to participate 
(Research).
2. Baseline Visit (Prior to Treatment) at Day 0
Within three weeks prior to your radiation therapy beginning, you will have the 
following procedures performed:
o
Obtain demographic and clinical information (Research)
o
Dynamic Contrast Enhanced Computed Tomography (DCE-CT) imaging 
performed to further assess your liver cancer or metastases (Research)

Consent and Authorization Form
COMIRB 18-2874
PI: Miften
Version Date: 01/16/2020
Page 4 of 11
Combined Biomed ICF and Compound HIPAA (CF-151.C, Effective 9-29-15)
3. First Fraction of Radiation Therapy at 1-2 weeks after Baseline Visit
You will have the following procedures performed when you come for you radiation 
therapy visit:
o
Dynamic Contrast Enhanced Computed Tomography (DCE-CT) Imaging 
performed to assess any possible changes to your liver cancer or 
metastases (Research)
4. Follow-up Visit after ~6 weeks following Radiation Therapy
Four to six weeks after your radiation therapy, you will have the following 
performed:
o
Dynamic Contrast Enhanced Computed Tomography (DCE-CT) Imaging 
performed to assess any possible changes to your liver cancer or 
metastases  (Research)
How long will I be on the study?
The total length of the time you will participating in this study is about 3 months. 
What are the possible discomforts or risks?
Discomforts you may experience while in this study include the same discomforts and risk 
which may be encountered during standard radiation treatment for liver cancer. These side 
effects are listed below and your physician will discuss the chances of these toxicities and 
their treatments in the specific context of your cancer and radiation plan. 
In addition to the below risks, this study may include risks that are unknown at this time.

Risk of Dynamic Contrast Enhanced Computed Tomography (DCE-CT) 
Imaging 
There is a risk of slightly higher doses of radiation because of the extra imaging 
scans. The additional exposure from this type of imaging is about 0.05% increase 
from the radiation you would otherwise be receiving from your radiation therapy.
In addition to the small increase of radiation, Dynamic Contrast Enhanced 
Computed Tomography (DCE-CT) scans have the following risks:

Consent and Authorization Form
COMIRB 18-2874
PI: Miften
Version Date: 01/16/2020
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Dynamic Contrast Enhanced Computed Tomography (DCE-CT) 
Imaging Known Risks
RARE, SOME MAY BE SERIOUS
In 100 people receiving contrast, 3 or fewer may have:

Contrast-induced nephropathy (damage to kidneys) – this risk low in 
patients without chronic renal impairment (2%) but is high (30%) in 
patients with chronic renal impairment

Pain 

Burning Sensation

Nausea

Hot Flashes

Warmth

Risk of Loss of Confidentiality
There is a risk that people outside of the research team will see your research 
information.  We will do all that we can to protect your information, but it cannot be 
guaranteed.

Risk of Pregnancy
If you become pregnant, the particular treatment or procedures involved in the study 
may involve risks to the embryo or fetus which are currently unclear. You should 
notify your physician immediately if there is a chance that you could be or become 
pregnant during radiation therapy. Discuss appropriate birth control methods with 
your doctor. 
What are the possible benefits of the study?
This study is designed for the researcher to learn more about Dynamic Contrast Enhanced 
Computed Tomography (DCE-CT) and how it could be used to make an improved 
diagnosis of patients with liver cancer. Physicians are hoping this information could provide 
information that may allow for a customizable treatment plan.

Consent and Authorization Form
COMIRB 18-2874
PI: Miften
Version Date: 01/16/2020
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This study is not designed to treat any illness or to improve your health.  Also, 
there may be risks, as discussed in the section describing the discomforts or 
risks.
Are there alternative treatments? 
You could proceed with Stereotactic Body Radiation Therapy without participating in this 
study.
You could also receive alternative treatments for your liver cancer or metastasis, or choose 
to get no treatment at all. 
You should talk to your doctor about your choices. Make sure you understand all of 
your choices before you decide to take part in this study. You may leave this study 
and still have these other choices available to you.
Who is paying for this study? 
This research is being sponsored by the University of Colorado Cancer Center. 
Will I be paid for being in the study?  
You will not be paid to be in the study. 
Will I have to pay for anything?
There are some medical treatments that you would have to get for your condition whether 
you were in this study or not. You will have to pay for these. There are other medical 
treatments that you will get because you are in this research study. The research study will 
pay for those. Those medical treatments are listed above in the “Study Procedures” 
section of the form under “Research.”
You and/or your health plan/ insurance company will need to pay for the standard of care 
items of treating your cancer.

Consent and Authorization Form
COMIRB 18-2874
PI: Miften
Version Date: 01/16/2020
Page 7 of 11
Combined Biomed ICF and Compound HIPAA (CF-151.C, Effective 9-29-15)
Is my participation voluntary?
Taking part in this study is voluntary. You have the right to choose not to take part in this 
study. If you choose to take part, you have the right to stop at any time. If you refuse or 
decide to withdraw later, you will not lose any benefits or rights to which you are entitled. 
If you leave this study, you will still receive your normal medical care. The only medical 
care that you will lose is the medical care you are getting as part of this study. You might 
be able to get that same kind of medical care outside of the study. Ask your study doctor. 
If there are any new findings during the study that may affect whether you want to continue 
to take part, you will be told about them.
Can I be removed from this study? 
The study doctor may decide to stop your participation without your permission if the study 
doctor thinks that being in the study may cause you harm, or for any other reason. 
 
What happens if I am injured or hurt during the study? 
If you have an injury while you are in this study, you should call Moyed Miften, PhD 
immediately. His phone number is (720) 848-0135. 
If you are hurt by this research, we will give you medical care. However, medical treatment 
will have to be provided by your insurance company for a research related injury. The term 
“research-related injury” means physical injury caused by drugs or procedures required by 
the study which are different from the medical treatment you would have received if you had 
not participated in the trial.
Who do I call if I have questions?
The researcher carrying out this study is Moyed Miften, PhD. You may ask any questions 
you have now. If you have questions, concerns, or complaints later, you may call Moyed 
Miften, PhD at (720) 848-0135. You will be given a copy of this form to keep.  

Consent and Authorization Form
COMIRB 18-2874
PI: Miften
Version Date: 01/16/2020
Page 8 of 11
Combined Biomed ICF and Compound HIPAA (CF-151.C, Effective 9-29-15)
You may have questions about your rights as someone in this study. You can call Moyed 
Miften, PhD with questions. You can also call the responsible Institutional Review Board 
(COMIRB). You can call them at 303-724-1055. 
Who will see my research information?
The University of Colorado Denver (UCD) and its affiliated hospitals have rules to 
protect information about you.  Federal and state laws including the Health Insurance 
Portability and Accountability Act (HIPAA) also protect your privacy. This part of the 
consent form tells you what information about you may be collected in this study and 
who might see or use it.  
The institutions involved in this study include:
University of Colorado Denver
University of Colorado Hospital
We cannot do this study without your permission to see, use and give out your 
information. You do not have to give us this permission. If you do not, then you may not 
join this study.  
We will see, use and disclose your information only as described in this form and in our 
Notice of Privacy Practices; however, people outside the UCD and its affiliate hospitals 
may not be covered by this obligation.
We will do everything we can to maintain the confidentiality of your personal 
information but confidentiality cannot be guaranteed. 
The use and disclosure of your information has no time limit. You can cancel your 
permission to use and disclose your information at any time by writing to the study’s 
Principal Investigator (PI), at the name and address listed below. If you do cancel your 
permission to use and disclose your information, your part in this study will end and no 
further information about you will be collected. Your cancellation would not affect 
information already collected in this study.
Moyed Miften, PhD
Department of Radiation Oncology
1665 Aurora Ct., Suite 1032
Mail Stop F706

Consent and Authorization Form
COMIRB 18-2874
PI: Miften
Version Date: 01/16/2020
Page 9 of 11
Combined Biomed ICF and Compound HIPAA (CF-151.C, Effective 9-29-15)
Aurora, CO 80045
Both the research records that identify you and the consent form signed by you may be 
looked at by others who have a legal right to see that information, such as:  

Federal offices such as the Food and Drug Administration (FDA) and the Office 
of Human Research Protections (OHRP) that protect research subjects like you.

People at the Colorado Multiple Institutional Review Board (COMIRB)

The study doctor and the rest of the study team.

Officials at the institution where the research is conducted and officials at other 
institutions involved in this study who are in charge of making sure that we follow 
all of the rules for research
We might talk about this research study at meetings. We might also print the results of 
this research study in relevant journals, but we will always keep the names of the 
research subjects, like you, private. 
You have the right to request access to your personal health information from the 
Investigator. 
Information about you that will be seen, collected, used and disclosed for these 
procedures:

Name and Demographic Information (age, sex, ethnicity, address, phone 
number, etc.)

Portions of your previous and current Medical Records that are relevant to this 
study, including but not limited to Diagnosis(es), History and Physical, laboratory 
or tissue studies, radiology studies, procedure results

Research Visit and Research Test records

Billing or financial information
What happens to the Data that are collected in this study? 
Scientists at the University of Colorado Denver and the hospitals involved in this study 
work to find the causes and cures of disease.  The data collected from you during this 
study are important to this study and to future research.  If you join this study:

The data given by you to the investigators for this research no longer belong to you.  

Both the investigators and any sponsor of this research may study your data 
collected from you.

Consent and Authorization Form
COMIRB 18-2874
PI: Miften
Version Date: 01/16/2020
Page 10 of 11
Combined Biomed ICF and Compound HIPAA (CF-151.C, Effective 9-29-15)
•
If data are in a form that identifies you, UCD or the hospitals involved in this study 
may use them for future research only with your consent or Institutional Review 
Board (IRB) approval.
•
Any product or idea created by the researchers working on this study will not belong 
to you.
•
There is no plan for you to receive any financial benefit from the creation, use or 
sale of such a product or idea. 
Agreement to participate in this study and use my data
I have read this paper about the study or it was read to me. I understand the possible risks 
and benefits of this study. I understand and authorize the access, use and disclosure of my 
information as stated in this form. I know that being in this study is voluntary. I choose to 
be in this study. I will get a signed and dated copy of this consent form. 
Signature:
Date:
Print Name:
Consent form explained by:
Date:
Print Name:
A signature line for a witness is required for consent of 
non-reading subjects and consent using a short form.
Witness Signature:  
  Date:  
Witness Print Name:  
Witness of Signature

Witness of consent process


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COMIRB 18-2874
PI: Miften
Version Date: 01/16/2020
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