Clinical trial NCT01666808
Conditions: Prostate Cancer
Sponsor: Emory University
Start date: 2012-09-01; Completion date: 2022-04-18
Enrollment: 165 participants; Allocation: RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
Investigators will perform a study with 162 patients in whom there is a strong suspicion of prostate cancer that has returned to the body after having a prostatectomy. Half of these patients will have radiotherapy decision-making and delivery per the usual routine, and half of these patients will have the radiotherapy decision and volumes guided by the FACBC test (anti-1-amino-3-\[18F\]fluorocyclobutane-1-carboxylic acid (anti-3- \[18F\]FACBC). The major goal of the investigation is to see whether the FACBC improves the selection and the cancer control rates of post-surgery patients with a rising PSA who undergo radiotherapy.

Detailed description:
Prostate cancer is the most common solid tumor, with approximately 200,000 new cases diagnosed per year. Several different local therapies are available for treatment, including surgery and radiotherapy Significant advances have been made in the technical aspects of surgery and of radiotherapy which have improved both the cancer control outcomes as well as the morbidity of treatment. Despite these significant advances, approximately 30% of patients treated with definitive local therapy experience recurrent disease. Recurrent disease after prostatectomy usually manifests with rising PSA (blood test for prostate cancer). The PSA level is often of limited use in differentiating local recurrence (ie. recurrence in the prostate bed) from recurrence outside of the prostate bed ( extra-prostatic recurrence).

One PET radiotracer which has shown promise in the staging and restaging of patients with prostate carcinoma is anti-1-amino-3-\[18F\]fluorocyclobutane-1-carboxylic acid (anti-3-\[18F\]FACBC) which is a synthetic amino acid analog. FACBC demonstrated higher accuracy compared with 111Indium-capromab-pendetide in the restaging of patients with suspected recurrent prostate carcinoma.

The major goal in this proposed investigation is to use advanced molecular imaging to better guide post-prostatectomy decision making, in terms of guiding the decision to deliver radiotherapy, and in terms of the exact areas treated with radiotherapy.

Investigators will perform a study with 162 patients in whom there is a strong suspicion of prostate cancer that has returned to the body after having a prostatectomy. Half of these patients will have radiotherapy decision-making and delivery per the usual routine, and half of these patients will have the radiotherapy decision and volumes guided by the FACBC test. The major goal of the investigation is to see whether the FACBC improves the selection and the cancer control rates of post-surgery patients with a rising PSA who undergo radiotherapy.

Arms: arm 1: A trial group in which anti-3-\[18F\]FACBC PET-CT is used to guide radiotherapy decisions and radiotherapy treatment volumes. arm 2: A control group whose treatment decisions will be made based on conventional imaging - bone scan and abdominopelvic CT and/or MR scan.
Interventions: intervention 1: FACBC intervention 2: Radiation therapy
Intervention descriptions: intervention 1: FACBC is given intravenously prior to PET scan, radiotherapy decisions and treatment guided by PET findings intervention 2: External beam radiotherapy to prostate bed +/- pelvic lymph nodes; final dose of 66.6 Gy.

Protocol documents:
Prot_SAP_001.pdf: 
Advanced Molecular Imaging with anti-3-[18F]FACBC PET-CT to Improve the Selection 
and Outcomes of Prostate Cancer Patients Receiving Post-prostatectomy Radiotherapy
NCT01666808 
Date: 02/24/2017


1
Advanced Molecular Imaging with anti-3-[18F]FACBC PET-CT to Improve 
the Selection and Outcomes of Prostate Cancer Patients Receiving Post-
prostatectomy Radiotherapy
Principal Investigator: Ashesh B. Jani, MD,MSEE
Department of Radiation Oncology
 
Co-Investigators
David M Schuster, MD (Nuclear Medicine)
Peter J. Rossi, MD (Radiation Oncology)
Karen Godette, MD (Radiation Oncology)
Raghuveer Halkar, M.D. (Nuclear Medicine)
Mark Goodman, Ph.D. (Radiology)
Zhengjia Chen, Ph.D. (Biostatistics)
Peter Nieh, M.D. (Urology)
Viraj Master, M.D., Ph.D (Urology)
Omer Kucuk, M.D (Medical Oncology) 
Funding Source: National Institutes of Health (NIH R01 CA169188-01)
Version    02-24-2017


2
Table of Contents
1.0
Abstract...............................................................................................................................................3
2.0
Schema................................................................................................................................................4
2.1Eligibility Checklist………………………………………………………………..…… .............5
3.0
Introduction.........................................................................................................................................6
4.0
Objectives (including Specific Aims).................................................................................................8
4.1 Study Endpoints…………………………………………………..……………………………..9
5.0
Preliminary Studies.............................................................................................................................10
6.0
Study Design and Methods .................................................................................................................15
6.1 anti-3-[18F]FACBC Radiolabeling……………………………………………......…… 16
6.2 PET Acquisition…………………………………………………………………..…… 16
6.2.1 FDA Reporting and Laboratory Requirements……………………………. 17
6.3 Patient Assessment: Image Analysis ………………………………………….….....… 17
6.4 Correlation of Histopathology with Imaging ………………………………………..…18
6.5 Patient follow-up…………………………………………………………………….… 18 
7.0 
Participant Selection and Treatment…………………….……………………………………...... ....19
7.1 Inclusion Criteria ……………………………………………................................…… 19
7.2 Exclusion Criteria……………………………………………................................…… 19
7.3 Pretreatment Evaluations and Registration Procedures………… …….....................… 19
7.3.1 Pretreatment Evaluations…………………………………………………….19
7.3.2 Registration Procedures……………………………………………………... 20
7.4 FACBC Details…………………………………………………………………...…….20
7.5 Radiation Therapy Details…………………………..……….....……………….……….21
7.5.1 Dose Specifications……………………………………………………………21
7.5.2 Technical Factors [Equipment, energies] ……………………………………21
7.5.3 Localization, Simulation, and Immobilization ………………………………21
7.5.4 Treatment Planning/Target Volumes ………………………………..…….…21
7.5.4.1 Prostate Bed Planning ………………………………………..……21
7.5.4.1.1 CTV – Arm A…………………………………..….……21
7.5.4.1.2 CTV – Arm B……………………………………..….…23
7.5.4.1.3 PTV – Arm A or Arm B…………………………………23
7.5.4.1.4 Normal Tissue Definitions – Arm A or Arm B………….23
7.5.4.1.5 Planning Parameters – Arm A or Arm B…………….….24
7.5.4.2 Pelvic Lymph Node Radiotherapy (PLNRT) planning …………...24
7.5.4.2.1 Arm A……………………………………………………24
7.5.4.2.2 Arm B……………………………………………………26
7.5.4.2.3 Critical Structures – Arm A or Arm B…………………..26
7.5.5 Documentation Requirements…………………………………………………26
7.5.6 Compliance Criteria……………………………………………………..……..27
7.5.6.1 Dose Heterogeneity…………………………………………………27
7.5.6.2 Normal Tissue Deviations………………………………….……....27
7.5.6.3 Radiotherapy Quality Assurance Reviews ………………………....27
7.5.6.4 Radiation Adverse Events………………………………………..…28
8.0 
Patient Assessments............................................................................................................................29
9.0 
Statistical Considerations....................................................................................................................30
10.0
Adverse Event Reporting....................................................................................................................33
11.0
Data Safety Monitoring Plan ..............................................................................................................36
12.0
References...........................................................................................................................................37
13.0
Appendices..........................................................................................................................................42


3
1.0 Abstract
Our overall goal is to improve the long term biochemical free survival of patients with recurrent 
prostate carcinoma by altering the current decision algorithm through the ability of advanced 
molecular imaging to guide the appropriate selection of patients who will benefit from salvage 
radiotherapy. Approximately 50% of patients who have undergone post-prostatectomy 
radiotherapy after Prostate Specific Antigen (PSA) failure or biopsy proven prostate bed 
recurrence manifest subsequent systemic disease, in part, because conventional imaging 
methods fail to adequately differentiate prostatic from extraprostatic recurrence. In the post-
prostatectomy setting, both under-treatment and over-treatment occur based on existing 
strategies, and appropriately directing radiotherapy is an unmet public health need in this 
population. We plan to leverage advanced molecular imaging with the positron emission 
tomography (PET) radiotracer anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid (anti-3-
[18F]FACBC) which in preliminary data is able to differentiate prostatic from extra-prostatic 
recurrence even at low PSA levels. Doing so will enable more appropriate selection of patients 
who will benefit from salvage radiotherapy and to achieve durable response at higher PSA 
levels than previously believed. 
     We hypothesize that if patients are appropriately selected for salvage radiotherapy with the 
aid of newly available advanced molecular imaging with anti-3-[18F]FACBC PET-CT, a 
significantly higher proportion will achieve long-term cure and at higher PSA levels than via 
conventional treatment algorithms. We also hypothesize that the use of advanced molecular 
imaging will alter post-prostatectomy radiotherapy algorithms both in decision to treat and in 
planning volumes. 
     To test these two hypothesis, we plan to conduct a prospective randomized clinical trial in 
which patients will be treated with salvage radiotherapy after conventional imaging methods in 
the control arm (A) and with the addition of anti-3-[18F]FACBC PET-CT in the trial arm (B). We 
will explore the role of anti-3-[18F]FACBC PET-CT in (1) controlling prostate cancer that would 
otherwise generally not be treated with post-prostatectomy radiotherapy, and improving prostate 
cancer control in patients that would generally be considered for radiotherapy, (2) guiding 
radiotherapy decisions, both in the overall decision to offer radiotherapy and in the decision to 
guide the general radiation field (prostate bed versus pelvis), and (3) influencing the target 
volume and overlap of normal structures when planning and delivering radiotherapy. The work 
will have significant implications for improving the outcomes of post-prostatectomy patients, not 
just for the use of anti-3-[18F]FACBC but for the application of novel imaging to guide post-
prostatectomy radiotherapy.


4
2.0 Schema – 


5
2.1 Eligibility Checklist
___(Y) 1. Adenocarcinoma of the prostate, post radical-prostatectomy
___(Y) 2. Detectable PSA
___(Y) 3. Negative technetium 99-m MDP or F-18 PET bone scan for skeletal metastasis
___(Y) 4. CT and/or MR scan of abdomen and pelvis which does not suggest presence of 
metastatic disease outside of the pelvis
___(Y) 5. ECOG/Zubrod Performance status of 0-2
___(Y) 6. Age over 18
___(N) 7. Contraindications to radiotherapy (including active inflammatory bowel disease or 
prior pelvic radiotherapy)
___(N) 8. Inability to undergo anti-3-[18F]FACBC PET-CT
___(N) 9. Metastatic disease outside of pelvis on any imaging or biopsy
___(N) 10. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease 
free for a minimum of 3 years
___(N) 11. Severe acute co-morbidity, defined as follows:
o
Unstable angina and/or congestive heart failure requiring 
hospitalization in the last 3 months
o
Transmural myocardial infarction within the last 6 months
o
Acute bacterial or fungal infection requiring intravenous antibiotics at 
the time of registration
o
Chronic Obstructive Pulmonary Disease exacerbation or other 
respiratory illness requiring hospitalization or precluding study therapy 
at the time of registration 
o
Acquired Immune Deficiency Syndrome (AIDS) based upon current 
CDC definition; note, however, that HIV testing is not required for entry 
into this protocol. The need to exclude patients with AIDS from this 
protocol is necessary because the treatments involved in this protocol 
may be significantly immunosuppressive. Protocol-specific 
requirements may also exclude immunocompromised patients
___(Y) 12. Willingness to undergo pelvic radiotherapy. 


6
3.0  Introduction 
Prostate cancer is the most common solid tumor, with approximately 200,000 new cases 
diagnosed per year. Several different local therapies are available for treatment, including 
surgery and radiotherapy (1). Significant advances have been made in the technical aspects of 
surgery and of radiotherapy which have improved both the cancer control outcomes as well as 
the morbidity of treatment. 
Despite these significant advances, approximately 30% of patients treated with definitive 
local therapy experience recurrent disease (2, 3). Recurrent disease after prostatectomy usually 
manifests with rising PSA. The PSA level is often of limited use in the differentiation of local 
from extra-prostatic recurrence, though the rate of PSA rise may have some value (4).
The differentiation of local from regional from distant recurrence is of critical importance 
since salvage techniques can cure disease confined to the surgical field. If pelvic nodal 
involvement is suspected, radiation fields can be extended to include the pelvic nodes (5-7). If a 
patient is not a candidate for salvage radiotherapy, he will likely be treated with systemic long 
term hormonal therapy which is expensive and result in significant morbidity, also leading to 
increased healthcare expenditures. Hormonal therapy, particularly long-term hormone therapy, 
can cause vasomotor symptoms, depression, loss of cognitive function, sexual dysfunction, loss 
of muscle mass, weight gain, shrinkage of genitalia, breast tenderness/gynecomastia, 
osteoporosis, risk of bone fracture, changes in lipid profile, glucose intolerance and 
cardiovascular complications (8-11). This morbidity of long-term hormones can be avoided if the 
PSA can be controlled with radiotherapy. 
Appropriate patient selection for radiotherapy is important. The decision to offer 
radiotherapy in the post-prostatectomy setting is somewhat controversial and based on many 
factors, including pre-prostatectomy disease factors, post-prostatectomy PSA nadir, PSA 
velocity, and absolute PSA level (12-25). The last item, the absolute PSA, is perhaps the most 
commonly used, so that in face of an elevated PSA greater than 2.0 ng/ml, patients may not be 
offered potential curative radiotherapy because of the belief that the recurrence has a high 
probability of being systemic. In a recent study by Schuster et al (submitted, Journal of Clinical 
Oncology) based on data from the NIH sponsored clinical trial of anti-3-[18F]FACBC with 
recurrent prostate carcinoma (5R01CA129356), 3/13 patients in the cohort of those with PSA 
>10 ng/ml were true negative for extraprostatic spread, and thus could have been potential 
candidates for salvage radiotherapy. Similarly, with low PSA values, patients may be offered 
radiation therapy. Yet, occult prostate carcinoma may be extraprostatic even at these PSA 
levels, and thus radiotherapy would be futile or could have been modified to include the pelvic 
nodes. In this same study, 4/12 patients in the cohort of those with PSA <2.0 ng/ml had occult 
metastatic disease outside of the prostate bed undiscovered on conventional imaging. If these 
patients had been offered salvage therapy, it would likely have been ineffective since disease 
had spread beyond normal fields of local therapy. 
Thus, imaging plays a central role in the differentiation of prostatic from extraprostatic 
recurrence. Conventional methodology to detect extra-prostatic nodal involvement including 
computed tomography (CT), magnetic resonance imaging (MR), transrectal ultrasound, and 
111Indium-capromab-pendetide (ProstaScint) (EUSA Pharma, Langhorne, PA) suffer from poor 
diagnostic performance with approximately 20-50% reported sensitivity (12, 26-33). ProstaScint 
had been studied to potentially select patients for salvage radiotherapy after PSA relapse with 
discouraging results (12, 34). Bone scanning with Tc-99mMDP is highly sensitive for the 
detection of bone metastasis, but there is low yield with PSA less than 10 ng/ml (35). To date, 
no established imaging test has demonstrated a role in a prospective setting in improving 
outcomes of post-prostatectomy radiotherapy. For this reason, newer methods such as diffusion 
weighted MR (DWMR) and positron emission tomography (PET) with molecular radiotracers are 
currently under study for the characterization of post therapy recurrence (36-44). The choline 


7
Post radical prostatectomy PSA 1.1. anti-3-
[18F]FACBC (a and b) and 111Indium-
capromab-pendetide (c and d). Intense 
uptake on axial anti-3-[18F]FACBC (arrow in 
a) and fused images (arrow in b) in 5 mm 
left obturator lymph node biopsy proven 
recurrence. No uptake in same region on 
111Indium-capromab-pendetide (arrow in 
c) and fused images (arrow in d).
PET radiotracers have also been suggested as a means to individualize post-prostatectomy 
treatment decisions (41). Yet the sensitivity of most imaging techniques including choline based 
radiotracers is dependent upon PSA level, doubling time, and velocity (41, 45, 46).
One PET radiotracer which has shown promise in the staging and restaging of patients 
with prostate carcinoma is anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid (anti-3-
[18F]FACBC) which is a synthetic amino acid analog with little renal excretion and transport via 
sodium dependent and independent pathways (47-49). In a recent study, anti-3-[18F]FACBC 
demonstrated higher accuracy compared with 111Indium-capromab-pendetide in the restaging of 
patients with suspected recurrent prostate carcinoma (50). The figure below demonstrates the 
ability of anti-3-[18F]FACBC PET-CT to detect extraprostatic involvement in a patient with 
negative ProstaScint.
Most importantly, as noted in our preliminary data below, anti-3-[18F]FACBC PET-CT maintains 
excellent diagnostic performance in the differentiation of prostatic from extra-prostatic 
recurrence across all PSA levels.
Our central hypothesis is if patients are appropriately selected for salvage radiotherapy with the 
aid of newly available advanced molecular imaging with anti-3-[18F]FACBC PET-CT, a 
significantly higher proportion will achieve long-term cure and at higher PSA levels than via 
conventional treatment algorithms. We will use anti-3-[18F]FACBC as an imaging vehicle to 
appropriately select patients in order to (1) control prostate cancer that would otherwise 
generally not be treated with post-prostatectomy radiotherapy, and improve prostate cancer 
control in patients that would generally be considered for radiotherapy, (2) guide radiotherapy 
decisions, both in the overall decision to offer radiotherapy and in the decision to guide the 
general radiation field (prostate bed versus pelvis), and (3) influence the target volume and 
overlap of normal structures when planning and delivering radiotherapy. The work will have 
significant implications for improving the outcomes of post-prostatectomy patients and for the 
application of novel imaging to guide post-prostatectomy radiotherapy. 
Study Sites: 
Note that this protocol is intended to be open initially at Emory University Hospital Clifton, Emory 
University Hospital Midtown, and Grady Memorial Hospital. The protocol is also intended to be 
open and available to the members of the Georgia Center for Oncology Research and 
Education (Georgia CORE – an organization which intends to increase the available cancer 
trials in the state of Georgia). Though Georgia CORE has provided written support [for the NIH 
R01 grant in support of this current protocol] to assist in trial accrual, as a formal contract 
between Emory CTO and Georgia CORE for this clinical is currently pending, we will amend this 
protocol at a later date once this formal contract is finalized.  
anti-3-[18F]FACBC 
ProstaScint


8
4.0 Objectives
Imaging techniques have typically been evaluated in terms of diagnostic performance verified 
usually with biopsy or clinical follow-up; truth as an endpoint has usually been that of histology. 
anti-3-[18F]FACBC PET-CT has been studied in this regard as well (47, 50). There have been 
retrospective analyses and reviews analyzing the role of ProstaScint which ultimately were 
negative for the utility of anti-PSMA antibody imaging in prostate control outcomes. In fact the 
study PI’s have considerable expertise in exploring the role of ProstaScint (51-54) and in 
comparison of ProstaScint to anti-3-[18F]FACBC PET-CT (50). There are ongoing prospective 
trials examining the role of androgen deprivation and field size (Radiation Therapy Oncology 
Group [RTOG] Protocol #0534), systemic therapy (RTOG Protocol #0622), and the timing of 
radiotherapy (MRC RADICALS Trial [Protocol NCT00541047] and Trans-Tasmanian Radiation 
Oncology Group [Protocol NCT00860652]) but no current prospective trials evaluating the role 
of advanced molecular imaging. Our study will involve a prospective randomized trial examining 
the impact of a novel imaging technique in guiding post-prostatectomy radiotherapy outcomes, 
decision making, and treatment planning.
Our major goal in this proposed investigation is to use advanced molecular imaging to better 
guide post-prostatectomy decision making. 
Specific Aim 1:  To improve the outcomes of post-prostatectomy radiotherapy prostate 
cancer patients using advanced molecular imaging with anti-3-[18F]FACBC PET-CT 
We hypothesize that the high failure rate of salvage radiotherapy in the post-prostatectomy 
patient population is secondary to lack of adequate imaging to identify extraprostatic spread of 
recurrent tumor which would preclude radiotherapy or result in modification of radiotherapy 
fields. Thus, a patient who normally would be considered for salvage radiation therapy because 
of a low PSA value may be spared needless radiotherapy if carcinoma is discovered outside the 
pelvis through the use of advanced molecular imaging techniques. Similarly, a patient who may 
otherwise not have been considered for salvage radiotherapy may be able to undergo potential 
curative salvage techniques because of the high negative predictive value of advanced 
molecular imaging. Our preliminary data strongly suggests that anti-3-[18F]FACBC PET-CT is 
the correct imaging vehicle for these decisions where others have failed.
Specific Aim 2:  To establish the role of advanced molecular imaging with anti-3-
[18F]FACBC PET-CT in influencing post-prostatectomy radiotherapy decision-making. 
As described above, the use of diagnostic imaging to guide radiotherapy is in its infancy. 
Current field design for prostate carcinoma radiotherapy mainly relies on the planning CT scan, 
with no novel imaging added beyond the bone scan and diagnostic CT scan and MRI in some 
situations. Adding imaging with advanced molecular methods will not only affect decisions to 
provide salvage radiotherapy, but also influence therapy fields, extending the potentially curative 
benefits of salvage techniques. For example, if internal iliac nodes are identified to be malignant 
with the use of anti-3-[18F]FACBC PET-CT, those areas could have radiation fields extended or 
targeted with IMRT to increase likelihood of biochemical control. 
Specific Aim 3: To establish the role of advanced molecular imaging (with anti-3-
[18F]FACBC) in altering radiotherapy treatment volumes. 
Utilizing novel aspects of multimodality image fusion to individualize treatment volumes 


9
As our study will evaluate the role of a PET radiotracer in post-prostatectomy radiotherapy, 
there are several novel aspects of multi-modality image fusion that will be explored in this study. 
Successful completion of this process will pave the way for multi-modality registration of other 
novel radiotracers in the future. 
4.1 Study Endpoints: 
Primary endpoint (on which power calculations are based) is: 
       3-year failure-free survival (Specific Aim 1) 
see section 6.5 for definition of failure 
Secondary endpoints: 
(a) Radiotherapy Decision endpoints (Specific Aim 2)
a.
Decision changes regarding radiotherapy versus no radiotherapy
b.
Decision changes regarding whole-pelvis versus local fields
c.
Total decision changes
(b) Volume-definition and dosimetric endpoints (Specific Aim 3)
a.
Prostate bed clinical target volume (CTV) – absolute volume
b.
Prostate bed planning target volume (PTV) – absolute volume
c.
PTV dosimetric endpoints (V100 and V110)
d.
Rectum dosimetric endpoints (V40 and V65)
e.
Bladder dosimetric endpoints (V40 and V65) 
(c) Toxicity Endpoints – provider-reported (CTCAE v4.0 criteria) [see Appendix 4]
a.
Rate of ≥ Grade 2 Acute GU toxicity
b.
Rate of ≥ Grade 2 Acute GI toxicity
c.
Rate of ≥ Grade 2 Late GU toxicity
d.
Rate of ≥ Grade 2 Late GI toxicity
(d) Toxicity Endpoints – patient-reported on EPIC [see Appendix 2]
a.
EPIC GU domain (Question 5) score [range 0-12]
b.
EPIC GI domain (Question 6) score [range 0-12]
c.
EPIC Sexual domain  (Question 7) score [range 0-12]
d.
EPIC total score [range 0-60]


10
5.0 PRELIMINARY STUDIES
Preliminary Data for Specific Aims 1 and 2: 
In a recent study published by our group in Radiology (50) anti-3-[18F]FACBC has been 
shown to have high sensitivity and specificity in the detection of extraprostatic extension 
of recurrent prostate carcinoma. Briefly, in this study, anti-3-[18F]FACBC PET-CT was 
compared with 111Indium-capromab-pendetide (ProstaScint) performed within 6 weeks of each 
other in 50 patients. anti-3-[18F]FACBC PET-CT demonstrated significantly higher sensitivity in 
the detection of recurrent prostate carcinoma in the prostate bed, but more importantly in 17 
patients in whom there was definitive consensus as to presence or absence of extraprostatic 
disease, there was 100% accuracy of anti-3-[18F]FACBC PET-CT in the detection of 
extraprostatic recurrence, while the sensitivity of ProstaScint was 10%. 
In a more recent analysis of a larger cohort, (submitted JCO), 117 patients with 
suspected recurrent prostate carcinoma were studied with anti-3-[18F]FACBC PET-CT. In the 46 
patients in whom there was definitive consensus on the presence or absence of extraprostatic 
disease, sensitivity to detect extraprostatic disease was 96.2% [CI: 80.4%, 99.9%], specificity 
95.0% [CI: 75.1%, 99.9%], accuracy 95.7% [CI: 85.2%, 99.5%], PPV 96.2% [CI: 80.4%, 99.9%] 
and NPV 95.0% [CI: 75.1%, 99.9%]. Diagnostic performance for extraprostatic detection 
remained high at all PSA levels. The table below is a breakdown of diagnostic performance by 
PSA levels. Of the 26/46 patients with proof of extraprostatic disease, 21 had node only, 3 had 
bone, 2 had both bone and nodal involvement. Lymph node sizes detected ranged from 4 mm 
to 2.3 cm (mean 1.2 cm ± 0.6) [typically, nodes smaller than 1.0 cm would not be deemed 
suspicious in the pelvis on cross sectional imaging]. Both observers were in initial agreement 
115/117 (98.3%) with kappa (SE) of 0.957 (0.03) for presence or absence of extraprostatic 
disease. Most importantly, in further analysis of data for this proposal, all 6 recurrent 
post-prostatectomy patients subsequently treated with local salvage radiotherapy based 
on negative anti-3-[18F]FACBC PET-CT for extra-prostatic disease achieved durable PSA 
nadir. In one of these patients, PSA at restaging, pre-salvage radiotherapy was 6.9 ng/ml.  
Table 1. Extraprostatic Disease Detection Diagnostic Performance (JCO submitted)
Thus, this preliminary data demonstrates excellent diagnostic performance of anti-3-
[18F]FACBC PET-CT in the recurrent disease setting justifying its utility in guiding 
management decisions. Below are two representative cases in which anti-3-[18F]FACBC PET-
CT can detect occult disease and potentially guide treatment decisions both at low and high 
PSA levels: 
PSA (ng/ml)
<2
≥2 and <5
≥5 and <10
≥10
All PSA
True Positive
4
5 
7
9
25 
True Negative
8 
4 
4
3
19 
False Positive
0
0
0
1
1
False Negative
0
0
1
0
1
Total
12 
9
12
13
46 
Sensitivity
100%
100%
87.5%
100%
96.2%
Specificity
100%
100%
100%
75%
95.0%
Accuracy
100%
100%
91.7%
92.3%
95.7%
PPV
100%
100%
100%
90%
96.2%
NPV
100%
100%
80%
100%
95.0%


11
Case 1: 68 year old patient post external beam radiation therapy and prostatectomy with rising 
PSA to 1.9 ng/ml and no abnormal findings in the prostate bed. CT (A) demonstrates 8 x 6 mm 
right internal iliac node (short arrow) with abnormal uptake on anti-3-[18F]FACBC PET (B) and 
fused PET-CT image (C) (long arrows) which was confirmed metastasis by CT guided biopsy. 
H&E stained section of the lymph node (40X) (D) demonstrates metastatic adenocarcinoma 
(arrow) from a prostate primary.
Case 2: 60 year old patient post EBRT, brachytherapy with rising PSA to 28.7 ng/ml and biopsy 
positive prostate bed. CT (A) demonstrates 1 cm left common iliac (short arrow) with abnormal 
uptake on anti-3-[18F]FACBC PET (B) and fused PET-CT image (C) (long arrows)  which was 
confirmed metastasis by laparoscopic biopsy. H&E stained section of the lymph node (40X) (D) 
demonstrates metastatic adenocarcinoma (arrow) from a prostate primary.
Preliminary Data for Specific Aim 3: 
Dr. Jani and Dr. Schuster (co-PI’s on the current proposal) and Dr. Fox (Co-I on the current 
proposal) have worked together on a case report [Jani AB, Fox TH, Whitaker D & Schuster D. 
Clinical Nuclear Medicine 2009] (55) in which the impact of  anti-3-[18F]FACBC PET-CT on 
radiotherapy treatment planning was analyzed in the setting of an intact prostate. For this case 
report, a rigid-body registration was performed, followed by a deformable image registration in 
order to fuse the anti-3-[18F]FACBC PET-CT with the radiotherapy planning CT. The results are 
shown below. Figure 1 depicts for a representative axial slice (a) the radiotherapy planning CT, 
(b) the anti-3-[18F]FACBC PET-CT, and (c) the registered image. Figure 2 shows how the anti-3-
[18F]FACBC image could then be contoured on three levels (A) upper, (B) mid, and (C) lower on 
the  radiotherapy planning CT to define (GTVFACBC [pink]). Finally, Figure 3 shows (A) an mid-
level axial representation of the radiotherapy isodose curves of the treatment plan and (B) 
corresponding dose-volume histograms of the planning target volumes (red, green and aqua, 
corresponding to various phases of the treatment), bladder (blue), and rectum (brown)
A
B
C
D
A
B
C
D


12
 
As shown in Figures 1 through 3 above, the process of registering and using the anti-3-
[18F]FACBC PET-CT information to design a radiotherapy treatment plan in the setting of an 
intact prostate has been established. For the current proposal, the rigid and deformable image 
methods will need to be modified for the prostate bed as the patient population under study is 
post-prostatectomy. The aim of registration is to establish an exact point-to-point 
correspondence (coordinate system transformation) between the voxels of the anti-[18F]FACBC 
PET-CT with the CT simulation dataset, making direct comparison possible. A rigid coordinate 
transformation is when only translations in three orthogonal directions and rotations in three 
directions are allowed.  The use of rigid registration may not provide accurate results since the 
patient can be positioned differently between imaging scans as well the internal organs can 
change position and shape.  In the case of prostate imaging, this may be due to changes in 
volume for internal organs such as bladder and rectum.  Deformable or elastic registration 
methods can be employed for these situations but it is not a trivial matter. Deformable image 
registration extracts structures from one image and elastically deforms it to fit the second image.  
With the deformable registration methods, the optimization algorithm is locally defined and 
calculated in small iterative steps using splines to mathematically represent the surfaces. 
Figure 1
Figure 3
Figure 2


13
Several computational models for deformable registration have been proposed with the 
most commonly used being the fluid-flow approach, BSpline, and the finite element approach 
(FEM). Each model is applied to a particular image registration problem depending and being 
restricted to the type of assumptions made concerning the nature of the images to be 
registered. Especially relevant to the CT-CT registration problem addressed in this proposal is 
the BSpline technique (56-58) combined with the Mattes formulation of the mutual information 
metric. The performance and characteristics of the BSpline model have been intensively studied 
(56, 58, 59) the model being applied to CT-CT (60-62) or 2D-3D (63) registrations with an 
accuracy of 3 mm. 
In the BSpline model, the input image is divided into a grid with N3 cells. The corner of a 
lattice cell is referred to as a node and is indexed by i (i=1, 2, …N3). The displacement of a node 
i is specified by a vector 
 and the displacement vectors, {
}, of a collection of nodes 
ix
ix
characterize the tissue deformation. The displacement at a location 
 on the image is deduced 
x
by fitting a polynomial expressed using the basis spline (BSpline) to the grid nodes 
. One of 
ix
the main advantages of using the spline model is that the deformation is interpolated between 
grid points, making it stable to pixel-level noise. Unlike other spline models, the B-Splines are 
locally controlled. That is, the displacement of an interpolation point is influenced only by that of 
the closest grid points and changing a lattice node only affects the transformation regionally, 
making it efficient in describing local deformations.  Due to these features, the B-Spline model 
should perform well for fusing post-prostatectomy CT images.  
Generally speaking, the input to the image registration model are two images, whose content 
has to be correlated. The task is to find the coefficients of a transformation matrix, 
, that 

x
T
maps an arbitrary point 
 on one image to the corresponding point 
on the second image so 
x
'x
that the best possible match, as measured by the registration metric, is achieved. The metric is 
a usually constructed from the voxel intensities in the two images based on the image content, 
its choice for ranking different possible matching differentiating one algorithm from the others 
and being fundamental to the success of the image registration. As the metric we will select the 
Mattes implementation of the mutual information MI metric due to its speed, simplicity and 
stability to noise in the input images. The Mattes implementation does not use all voxels in the 
input images, rather it evaluates a random sample of the voxels and uses interpolation to 
evaluate the joint histogram, creating histograms that are less noisy if used as criteria for the 
optimization Mattes) Since only a percent of the input image voxels are used, the metric is faster 
than the metrics that are evaluated on the whole image. 
In the BSpline model, node displacements are adjusted iteratively to minimize the metric. The 
limited memory BFGS algorithm L-BFGS is a good candidate to optimize the system here, for its 
superior performance in dealing with high-dimensionality problems. To facilitate the optimization 
it is preferable that both the deformable model and the metric are differentiable (60). This 
condition is satisfied for the system that we are dealing with, as demonstrated in a previous 
mathematical work (64). Additionally, it is possible that L-BFGS may produce unrealistic 
deformations in finding the minimum of the metric. Similar to previous investigators (60), we will 
use the bounded version of L-BFGSB, where variables representing deformation magnitude are 
restricted to within certain limits.
Depending on initial registration results, changes will be accommodated in the BSpline 
model to increase accuracy and decrease computation times. Since noise and artifacts in the 
input images affect accuracy (56), a current trend is to restrict the deformations only to relevant 
image regions to increase algorithm stability by decreasing the number of control points. 
Additionally this approach permits a simple alternative to classical multi-modality metrics for the 
cases voxel intensities in the input images do not build a balanced histogram for evaluating the 
joint information (61). 


14
All calculations will be implemented using an open-source software toolkit named the 
Insight Toolkit (ITK), which consists of template-based codes for a large number of image 
visualization, segmentation and registration classes. The programs contained in ITK are easily 
extendable, making it an ideal platform for the development of image registration methods. A 
special filter permits connecting registration results to other medical software through the 
DICOM protocol.  Potential indicators of the correctness of the deformation field are differential 
operators such as Jacobian, and vectors representations of the warping map. The Jacobian is 
computed from the deformation field as a measure of the local tissue expansion or contraction, 
with negative values implicating that the transformation map has gone singular, an indication of 
an unrealistic situation. It is an efficient and intuitive clinical tool for the understanding of the 
deformation field as it summarizes in a simple number the local characteristics of the 
deformation field.
Once registered to the radiotherapy planning CT scan, the process of formally 
comparing pre- anti-3-[18F]FACBC vs post- anti-3-[18F]FACBC treatment plans (for Specific Aim 
3 of the current study) is well-known. Dr. Jani has led a prior team that has done this very 
analysis (using radioimmunoscintigraphy with ProstaScint) of volumetric and dosimetric 
comparisons of target volumes and their impact on dosimetry of surrounding structures, in prior 
publications (51, 54), and these methods can be readily extended to the anti-3-[18F]FACBC 
volumes. 


15
6.0 Study design and methods  
We will undertake a clinical trial of 162 patients post-prostatectomy with detectable PSA levels. 
Note that patients with any detectable PSA will be eligible, allowing patients who are and 
are not traditionally offered radiotherapy to be enrolled. Patients may or may not have 
biopsy proof of local recurrence, but will be under active consideration for salvage radiotherapy 
based on PSA and other clinical criteria. 
Patients will be stratified as follows:

Adverse Pathological Factor (Margin Status, Extra-capsular Extension, or Seminal 
Vesical Invasion, pathological node positive) (yes vs no)

PSA level (pre-radiation): (≤ 2.0 ng/mL vs > 2.0 ng/mL)

Intended use of Hormone Therapy (yes vs no)
Patients will be randomized to:
Arm A:  a control group whose treatment decisions will be made based on conventional 
imaging - bone scan and abdominopelvic CT scan; or 
Arm B:  a trial group in which anti-3-[18F]FACBC PET-CT is used to guide radiotherapy 
decisions and radiotherapy treatment volumes
For patients treated in Arm B,  we will compare initial (pre- anti-3-[18F]FACBC) versus final 
(post- anti-3-[18F]FACBC) treatment decisions regarding (a) the decision of whether to offer 
post-prostatectomy XRT, (b) the decision of whether to treat the pelvic lymph nodes in addition 
to the prostate bed. 
This will be accomplished via an intention to treat form that will be filled out prospectively by 
each treating radiation oncologist, before and after anti-3-[18F] FACBC PET-CT 
  Decisions on (a) whether to offer radiotherapy and (b) radiotherapy volume to be 
determined are charted
         Then an anti-3-[18F]FACBC PET-CT scan is done, with radiotherapy decisions as follows: 
           If extrapelvic uptake: 
no radiotherapy
           If pelvic uptake or pN1:  
radiotherapy to prostate bed + pelvic lymph nodes
           If prostate-bed only uptake:  radiotherapy to prostate bed only
           If no FACBC uptake:  
radiotherapy to prostate bed only
Radiotherapy plan designed first without anti-3-[18F]FACBC information.
Then anti-3-[18F]FACBC/planning CT fusion done to determine final treatment plan.
Note that in both arms A and B the use and duration of hormone therapy with radiotherapy is at 
the discretion of the treating physician. 
Follow-up
Each patient (Arms A and B) will be followed for a minimum of three years with PSA levels 
every 6 months and other clinical parameters to both measure presence and time to PSA 
failure, as well as manifestation of clinical failure as defined by macroscopic identifiable disease. 
Outcomes will be compared between groups in aggregate and stratified by PSA level. The 


16
endpoint will be failure-free survival after salvage radiotherapy - please see section 6.5 below 
for failure definition.
6.1 anti-3-[18F]FACBC Radiolabeling
Methods. We will prepare anti-3-[18F]FACBC by the GE FastLab Cassette System. Alternatively, 
by the automated synthesis developed by J. McConathy and M.M. Goodman (65) as outlined in 
Figure 3. The automated radiosynthesis of anti-3-[18F]FACBC will be carried out in a chemical 
process control unit (CPCU) with a computer interface. The two-step reaction sequence will 
involve incorporation of no-carrier-added potassium [18F]fluoride into a protected triflate 
precursor and deprotection using aqueous hydrochloric acid. The crude reaction mix will be 
passed in series through ion-retardation resin, an alumina-N SepPak®, an HLB cartridge and a 
0.22 µm sterile filter, and the resulting aqueous solution will be collected in a dose vial. The 
radiochemical purity of the product will be determined by TLC.  Additional chemical solvent 
purity will be measured by Gas Chromatography (GC). The total time for synthesis of anti-3-
[18F]FACBC after delivery of 18[F]fluoride will be ~70 minutes, and the average decay-corrected 
yield of anti-3-[18F]FACBC will be 24 ± 4 % (n = 40 runs, average ± standard error) in over 99% 
radiochemical purity . This procedure will provide 140-200 mCi of anti-[18F]FACBC at the end of 
synthesis. We have prepared greater than 30 batch productions for tumor imaging in volunteer 
subjects.
 
6. 2.   PET Acquisition
We have previously reported on the preparation of anti-3-[18F]FACBC (65). The radiotracer will be 
produced under the auspices of investigational new drug (IND) application 72,437. A GE FastLab 
cassette system will be employed. Scanning will conducted on a GE Discovery MV690 PET-CT scanner 
with time of flight capabilities and interpreted on a workstation utilizing MIMvista 5.2 (Cleveland, OH) 
software. All patients will fast for 4-6 hours before the anti-3-[18F]FACBC scan. After a CT scan of the 
abdomen and pelvis (80-120 mA; 120 kVp) with oral and without IV contrast, anti-3-[18F]FACBC (10 mCi; 
370 MBq) will be injected IV over 2 minutes. At 5 minutes, 4 consecutive 2.5 minutes per frame 
acquisitions (z axis FOV is: 15cm with 3 cm overlap per table position) will be obtained starting from the 
prostate level of the pelvis and extending superiorly to the diaphragm. At 16 minutes, this process will be 
repeated. Thus, 4-15.5 minute, and 16-27.5 minute acquisitions from the pelvis extending superiorly to 
the abdomen at the diaphragm will be obtained (Figure 1). This imaging schema is based on analysis of 
our data to date in which early and delayed uptake to 30 minutes yields the most diagnostic information. 
Imaging will be carried out with either HD mode and respiratory gating or TOF mode with or without 
respiratory gating. This timing is based upon our experience for best criteria in dual time point imaging to 
diagnose prostatic recurrence (50). Imaging above the diaphragm will not be carried out to best 
approximate standard of care CT scans of the abdomen and pelvis. Isolated prostate carcinoma 
metastasis above the diaphragm rarely occur. 
BocHN
CO2CH3
OSO2CF3
BocHN
CO2CH3
18F
H2N
CO2H
18F
a
b
anti-[18F]FACBC
a)K18F, K222, K2CO3; 90C b) 4 NHCl, 120 C
Figure 3. Synthesis 
of anti-FACBC


17
Minutes:  5-7.5    8-10.5   11-13.5   14-15.5                  16-18.5 19-21.5 22-24.5   25-27.5
Figure 16: CT of abdomen and pelvis followed by injection of anti-[18F]FACBC then PET 
scanning as above.
Summary of PET-CT Scanning Procedure
1) The patient will be placed in the tomographic gantry for a CT scan of the abdomen-
pelvis (80-120 mA) to be utilized for anatomic imaging and correction of emission data 
(approximately 1 minute). 
2) The patient will then receive a bolus of anti-[18F]FACBC injected IV over 1-2 minutes
3) The dosage will be approximately 10.0 mCi (370 MBq).
4) At 5 minutes after initial injection (3 minutes after injection ceases), a 2.5 minute per 
bed position PET acquisition will start at the pelvis with the inferior aspect of the 
acquisition to include the entire prostate or prostate bed. 
5) 4 bed positions will be obtained which should cover pelvis through abdomen to the 
diaphragm. 
6) This sequence will be repeated once.
7) The entire study including injection of radiotracer should take approximately 30 
minutes.
6.2.1 FDA Reporting and Laboratory Requirements
 (3) The patient will be called by the study nurse within one week of the scan to determine if 
there were any adverse events and the record of the phone conversation will be recorded in the 
patient chart. 
6.3 Patient Assessment: Image Analysis 
Methods. The methods of image analysis to be used for the anti-[18F]FACBC PET-CT are as 
follows:
1) Images will be reconstructed with iterative technique (2 iterations, 28 subsets) and hardware 
fused (PET to CT) on a MimVista 5.2 or similar workstation which enables SUV (mean, 
maximum, total lesion activity) as well as standard size measurements of lesions. An edge 
seeking conformational volume of interest tool (PET Edge, MIMvista, Cleveland, OH) will 
typically utilized. If this is not possible due to anatomy a 1 cm ROI will be utilized. 
2) Visual inspection of the PET-CT images by 2 board certified nuclear medicine imagers who 
will be blinded to all history and other imaging. Each reader will assess images individually and 
any disagreement will be resolved by consensus. Thus, Z score will be calculated.
3) For anti-3-[18F]FACBC, uptake will be defined according to the following criteria in relation to 
background structures: mild (above blood pool but less than marrow), moderate (above or equal 


18
to marrow but less than liver), and intense (equal to or above liver). Visual analysis will aided by 
quantitative criteria of SUVmax lesion/SUVmean background. Maximum and mean SUV of each 
focus of abnormal uptake as well as background structures including liver, marrow at L3, aorta, 
and bladder will be recorded. For prostate beds as well as extra-prostatic sites such as lymph 
nodes and bone, abnormal moderate or intense focal uptake over background marrow which 
persist from early to delayed images will be considered prospectively positive. These criteria 
were used to analyze data in our study of anti-[18F]FACBC in recurrent disease (66). 
4) Confidence in interpretation for disease within the prostate bed and outside the bed will be 
recorded with the following scale on a per patient basis and any all recordable lymph nodes: 1-
defiinitvely negative; 2 -probably negative; 3 - indeterminate; 4 - probably positive; 5 – 
definitively positive.
5) In summary, we will record both visual and semi-quantitative analysis of the prostate 
bed, positive lymph nodes (greater than blood pool), and other structures such as 
skeletal foci on early and delayed time frames. We will use maximum and mean SUV as 
well as standard bidimensional size measurements. We will also record similar 
measurements on background structures such that we may derive uptake ratios.
6.4 Correlation of Histopathology with Imaging:
Every effort will be made to histologically confirm all anti-3-[18F]FACBC positive nodes or other 
foci. Any positive uptake per above will be treated as a true positive, unless it can be shown that 
the focus in question was biopsied and was definitively a false positive.
6.5 Patient follow-up
This randomized trial will us utilizing anti-3-[18F]FACBC as an imaging vehicle to (a) permit the 
selection of patients with high PSA levels who would not ordinarily be treated with radiotherapy, 
(b) improve biochemical control in post-prostatectomy patients treated with radiotherapy, and (c) 
result in different rates of toxicity than those treated with the current conventional approach. 
Using standard definition of failure [serum PSA value of 0.2ng/mL or more above the 
postradiotherapy nadir followed by another higher value, a continued rise in the serum 
PSA despite radiotherapy (RT), initiation of systemic therapy after completion of RT, or 
clinical progression] (21), Kaplan-Meier Survival curves will be generated for both Arms 
A and B and compared – the primary endpoint will be 3-year failure-free survival. 
This follow-up endpoint is appropriate for the current design as an adequate event rate at 3-
years was noted in one of the original salvage XRT series (67). Follow-up after the 5-year 
period of the grant, particularly for those patients enrolled in year 3, can be completed by a 
minimal-cost grant extension for follow-up only. 


19
7.0 Participant Selection and Treatment
7.1 Inclusion Criteria 

Adenocarcinoma of the prostate, post radical-prostatectomy

Detectable PSA

ECOG/Zubrod Performance Status of 0-2

Negative technetium 99-m MDP or F-18 PET bone scan for skeletal metastasis

CT or MR scan of abdomen and pelvis which does not suggest presence of 
metastatic disease outside of the pelvis

Willingness to undergo pelvic radiotherapy.
7.2 Exclusion Criteria

Contraindications to radiotherapy (including active inflammatory bowel disease or 
prior pelvic XRT)

Inability to undergo anti-3-[18F]FACBC PET-CT

Age under 18

Metastatic disease outside of pelvis on any imaging or biopsy

Prior invasive malignancy (except non-melanomatous skin cancer) unless disease 
free for a minimum of 3 years

Severe acute co-morbidity, defined as follows:
o
Unstable angina and/or congestive heart failure requiring hospitalization in 
the last 3 months
o
Transmural myocardial infarction within the last 6 months
o
Acute bacterial or fungal infection requiring intravenous antibiotics at the time 
of registration
o
Chronic Obstructive Pulmonary Disease exacerbation or other respiratory 
illness requiring hospitalization or precluding study therapy at the time of 
registration 
o
Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC 
definition; note, however, that HIV testing is not required for entry into this 
protocol. The need to exclude patients with AIDS from this protocol is 
necessary because the treatments involved in this protocol may be 
significantly immunosuppressive. Protocol-specific requirements may also 
exclude immunocompromised patients
7.3 Pre-treatment Evaluations & Registration Procedures
7.3.1 Pre-treatment evaluations: 
History and Physical (i.e., Symptom-directed examination)
ECOG/Zubrod Performance Status (see Appendix 1)
Pathology report (from radical prostatectomy)
Bone scan report
CT or MRI pelvis report
PSA
If ADT intended: Serum Testosterone; Serum AST or ALT
EPIC sheet (see Appendix 2)
Pre-FACBC Radiotherapy Decision / Attestation Sheet (see Appendix 3)


20
7.3.2 Registration/Randomization Process
Randomization Process will be done only after all pre-treatment evaluations have been 
completed and after the decisions on whether to offer radiotherapy (and general target volume), 
as attested on the pre-FACBC Radiotherapy Decision /Attestation Sheet the providing physician 
(see Appendix 3). 
Patients will be stratified as follows:

Adverse Pathological Factor (Margin Status, Extra-capsular Extension, or Seminal 
Vesical Invasion, pathological node positive) (yes vs no)

PSA level (pre-radiation): (≤ 2.0 ng/mL vs > 2.0 ng/mL)

Intended use of Hormone Therapy (yes vs no)
Randomization assignment will be performed by the study statistician through a standard 
random number generator. The subject will be assigned randomly to one of the two arms: 
Arm A: Standard/Control Arm
Arm B: FACBC arm
General treatment methodology of each of these arms is described in section 6.0 above. 
After randomization, information as to the enrollment arm will be shared with the PI, treating 
physician, and subject (ie, the treatment arm will not be masked). While ideally masking would 
be done (for both physicians and subject), in an imaging study this is  not feasible (it not 
generally not possible to obtain a ‘sham’ FACBC scan and the study investigators would not be 
in equipoise if an FACBC scan were obtained on all subjects and this information were to be 
withheld these subjects). 
Within 1 month of randomization, subjects on arm A will begin treatment (radiotherapy and/or 
hormones), and subjects on arm B will receive an FACBC scan. For subjects on arm B, 
treatment (radiotherapy and/or hormones) will begin within 1 month from the FACBC scan date. 
7.4 FACBC details
For subjects randomized to arm B, the FACBC scan will be done at Emory. This has been 
described in detail including post-scan laboratory test required by the FDA above in sections 
6.1-6.4 above. Patients will be responsible for their own travel. A travel allowance of 
approximately $100 per patient will be provided upon completion of all laboratory follow-up. The 
patient does not have to return to Emory for their follow-up laboratory work, but may provide this 
to the study nurse via fax, secure email, or mail.
The cost of the FACBC PET study will also be paid from the grant and will not be billed to 
insurance. All other diagnostic imaging costs as well as costs of biopsies if any, radiotherapy if 
any, and systemic therapy if any will be billed to insurance or paid out of pocket by the patient.


21
7.5 Radiation Therapy Details 
(modeled after Radiation Therapy Oncology Group Protocol 0534: 
http://www.rtog.org/ClinicalTrials/ProtocolTable/StudyDetails.aspx?study=0534)
7.5.1 Dose Specifications 
Radiotherapy dose will be specified to the Planning Target Volume (PTV), as described below. 
For the treatment methods outlined for prostate bed RT (IMRT), ≥ 95% of the PTV should 
receive the prescribed dose. The total dose to the prostate bed for all treatment arms is  64.8-
70.2 Gy at 1.8 Gy per fraction. 
7.5.2 Technical Factors [Equipment, energies]
Megavoltage equipment is required with effective photon energies ≥ 6 MV. IMRT is required.
7.5.3 Localization, Simulation, and Immobilization 
A urethrogram or MRI is recommended, but not required, to establish the most inferior portion of 
the prostate bed. Use of contrast, other than for the urethrogram, is discouraged. The 
placement of contrast in the rectum may cause the rectum to appear more anterior than it will be 
during treatment. Simulation should be with the rectum as empty as possible (an enema 1-2 
hours prior to simulation is encouraged) and with a moderately full bladder (the patient should 
not be uncomfortable at simulation and probably will have more difficulty maintaining a full 
bladder during treatment). An overly distended rectum can introduce a systematic positioning 
error that may increase the probability of missing the CTV. 
Immobilization of the hips and feet using a cradle should be considered. 
Contrast may be used for simulation but can distort the anatomy slightly and so is not 
recommended. The bladder should be reasonably full for simulation, keeping in mind that 
patients may not be able to maintain as full a bladder during radiotherapy. Having a somewhat 
full bladder at simulation ensures that the CTV will be of maximal dimensions.
A treatment planning CT scan will be required to define the clinical and planning target volumes, 
and the critical normal structures. The treatment planning CT will be acquired with the patient 
set up in the same position as for daily treatments. Each patient will be positioned in the supine 
position. Prone positioning for treatment is not permitted. Rectal balloons for planning and 
treatment are not permitted. The CT scan of the pelvis should start at or above the iliac crest 
down to below the perineum (below the ischial tuberosities). All tissues to be irradiated must be 
included in the CT scan. CT scan thickness should be ≤ 0.3 cm through the region that contains 
the target volumes. The regions above and below the target volume region may be scanned 
with slice thickness ≤ 1.0 cm.
7.5.4 Treatment Planning/Target Volumes 
7.5.4.1 Prostate Bed Planning 
7.5.4.1.1 CTV – Arm A
The seminal vesicles or remnants thereof, if identified on CT or MRI as being present, will 
receive the full dose. The immediate periprostatic bed surgical clips should receive the full dose. 
The CTV will extend from the top of the penile bulb inferiorly, or 1.5 cm below the urethrogram 


22
peak if done, to just above the pubic symphysis superiorly (at least for the anterior-most portion 
of the bladder). Laterally, the CTV will extend from the medial edge of one obturator internus 
muscle to the other. Anteriorly, the CTV will include the entire bladder neck until above the pubic 
symphysis, where a gradual reduction off of the anterior bladder is made. Superiorly, above the 
pubic symphysis, at least the posterior 2 cm of bladder should be included in the CTV, as well 
as the area between the bladder and rectum, to the anterior rectal wall. The CTV should extend 
superiorly to cover any clips in the seminal vesicle bed and the seminal vesicle remnants if 
present and should extend at least 2 cm above the pubic symphysis. Posteriorly, the CTV is 
defined by the anterior-most aspects of the anus-rectum. The CTV may be increased (not 
decreased) beyond these limits based on pre-prostatectomy imaging information.
A consensus definition of the prostate bed and an anatomically-based description should be 
considered in defining the CTV. There has been considerable variability in how the prostate bed 
has been defined in the past. Although consensus definitions are not based on clinical outcome, 
they are extremely valuable in making the transition from conventional to conformal volumes. 
The consensus definition is not much different than the CTV originally described above, but 
subtle differences are evident and should be considered. Either CTV definition will be accepted 
in this clinical trial.
1) Superiorly: The prostatic fossa CTV (PF-CTV) should extend superiorly from the level of the 
caudal vas deferens remnant. In some cases, the vas deferens remnant may be difficult to 
visualize. In the absence of gross disease or seminal vesicle remnants, the superior limit of the 
CTV should extend at least 2 cm and need not extend more than 3-4 cm above the level of the 
pubic symphysis. The consensus definition calls for “inclusion of the seminal vesicle remnants, if 
present, in the CTV if there is pathologic evidence of their involvement. However, inclusion of 
any seminal vesicle remnants seen is recommended.
2) Inferiorly: The PF-CTV should extend inferiorly to > 8-12 mm inferior to vesicourethral 
anastomosis (VUA). With axial CT imaging, the VUA can often be seen in the retropubic region 
as one slice below the most inferior urine-containing image (the bladder must be modestly full). 
Magnetic resonance (MR) imaging defines this landmark more clearly with the hyperintense 
urine signal on T2 images. Inferiorly, the border of the CTV should be at least 8-12 mm below 
the VUA. A sagittal reconstruction facilitates identification of the position of the VUA and the 
inferior border of the CTV below it. If visualization of the VUA is problematic due to image 
quality or surgical clip artifacts, the inferior limit of the CTV can extend to a level just above the 
penile bulb (same border as described above). It should be noted that there was considerable 
discussion about this definition versus extending the inferior border of the CTV to just above the 
penile bulb; both definitions were deemed acceptable.
3) Anteriorly: Below the superior border of the pubic symphysis, the anterior border is at the 
posterior aspect of the pubis. The CTV extends posteriorly to the rectum where it may be 
concave at the level of the VUA. At this level the lateral border extends to the levator ani. Above 
the pubic symphysis the anterior border should encompass the posterior 1-2 cm of the 
bladder wall at the minimum and posteriorly it is bounded by the mesorectal fascia. At this 
level the lateral border is the sacrorectogenitopubic fascia. This is not well-defined in textbooks. 
If in question, the lateral border should extend to the obturator internus muscle.
4) Posteriorly: The CTV extends posteriorly to the anterior rectal wall, but may be somewhat 
concave around the anterior-lateral aspect of the rectum to adequately encompass the prostate 
bed.


23
7.5.4.1.2 CTV – Arm B
For patients on Arm B, the CTV as defined in 7.5.4.1.1 above will be contoured and submitted to 
the Emory Radiation Oncology Department. The Radiation Oncology PI (Dr. Jani) will supervise 
registration of the FACBC scan with the planning CT scan for definition of the prostate bed CTV, 
which will be defined as the union of the CTV [in section 7.5.4.1.1 above] with the prostate bed 
uptake seen on the FACBC scan. 
7.5.4.1.3 PTV – Arm A or Arm B
The PTV margins should be 0.8 cm in all dimensions. A reduction of the PTV margin from 0.8 
cm to ≥ 0.6 cm to minimize rectal exposure will be considered a variation acceptable. A 
posterior margin of < 0.6 cm will be considered an unacceptable deviation. 
Care should be taken to conform the prescribed dose as closely to the PTV as possible, so as 
to avoid including the entire width of the rectum in the posterior blocked margin at the bladder 
neck-rectum interface. The planned dose between 64.8-70.2 Gy will be declared after the 
patient is planned and all dosimetric parameters finalized.
7.5.4.1.4 Normal Tissue Definitions – Arm A or Arm B
Normal tissues will be outlined as solid structures, including the rectum, bladder and femoral 
heads. The penile bulb will be outlined as a reference structure. No constraints will be placed on 
the penile bulb, but doses will be recorded. The rectum will be outlined from the anterior flexion 
of the rectosigmoid superiorly to the ischial tuberosities inferiorly. The entire bladder should be 
outlined down to the anastamosis. The DVH calculations will include doses to the entire bladder 
and the bladder minus the CTV (Bladder - CTV).The femoral heads should be outlined down to 
the region between the greater and lesser trochanters. The planning parameters outlined below 
for IMRT should be used as a guide; formal 3D-CRT normal tissue prostate bed constraints 
have not been the standard in the past and are not specified here. It should be possible to come 
close to achieving the constraints outlined for IMRT, at least within the variation range.
7.5.4.1.5 Planning Parameters – Arm A or Arm B
The plan will be deemed acceptable under the following conditions.
PTV: The dose marker levels for bladder and rectum have been modeled after prior studies in 
men treated definitively with IMRT for prostate cancer. At least 95% of the PTV should receive 
the prescribed dose (64.8-70.2 Gy); a variation acceptable will be noted if < 95% to 90% of the 
PTV receives the prescribed dose, and a deviation unacceptable will be noted if < 90% of the 
PTV receives the prescribed dose. The maximum dose within the PTV, above the prescribed 
dose, will be 15%; an acceptable variation will be > 15% to ≤ 20% and an unacceptable 
deviation will be > 20%.
Rectum: Less than or equal to 35% and 55% of the rectum should receive ≥ 65 Gy and ≥ 40 Gy, 
respectively. An acceptable variation will be noted if up to an additional 10% of the rectal 
volume at either cutpoint receives above the target doses specified. The inclusion of rectal 
volumes beyond these constraints will be considered a secondary acceptable variation and the 
extent of the variation should be recorded. In most patients, these constraints may be easily met 
and every attempt should be made to achieve the best dose distribution possible. The 


24
constraints will be harder to achieve in patients enrolled on Arm 3 (those receiving pelvic 
irradiation).
Bladder: Less than or equal to 50% and 70% of the bladder minus prostate bed CTV 
(Bladder - CTV) should receive ≥ 65 Gy and ≥ 40 Gy, respectively. The criteria for the bladder 
are relaxed because the dosimetric relationship of volume exposed to the specified marker 
doses is much less clear and the bladder neck is included in the CTV. Note that the DVH for the 
entire bladder should be recorded, but the bladder - CTV is the volume that should be used for 
the calculations described here. An acceptable primary variation will be noted if up to an 
additional 7.5% of the bladder volume receives above the target doses specified. The inclusion 
of bladder volumes beyond these constraints will be considered an
acceptable secondary protocol variation; it will not be considered a protocol violation. In some 
patients, the bladder will be relatively empty and the majority will be in the PTV.
Femoral Heads: Less than or equal to 10% of each femoral head should receive ≥ 50 Gy. A 
variation will be noted if up to an additional 5.0% of either femoral head receives > 50 Gy.
Penile Bulb: The penile bulb will be outlined as a reference structure. No constraints will be 
placed on the penile bulb, but doses will be recorded.
Small Bowel: See PLNRT section below.
Use of Cone Beam CT and Plan Adjustment: There may be cases in which the target and 
surrounding normal tissues are found not to be reproducible relative to the simulation CT and 
consequent plan. Replanning will invalidate the dosimetry and is considered a deviation. If all 
attempts to reproduce bladder and rectal filling by coaching the patient do not work and 
replanning is thought to be necessary, the patient should be replanned in the same supine 
position with the same target volumes as specified per the randomization. The patient will 
remain on the trial, despite the deviation.
7.5.4.2 Pelvic Lymph Node Radiotherapy (PLNRT) planning 
7.5.4.2.1 Pelvic Lymph Node Radiotherapy (PLNRT) planning – Arm A
For patients receiving PLNRT, the prostate bed and pelvic lymph nodes (CTV1/PTV1) will 
receive 45.0-50.4 Gy at 1.8 Gy per fraction. Once this is completed, a reduction will be made to 
deliver a total dose of 64.8-70.2 Gy at 1.8 Gy/fraction to the prostate bed (CTV2/PTV2). 
The CTV1 will include the obturator, external iliac, proximal internal iliac and common iliac 
nodes, estimated using the vascular structures, up to the level of L5-S1. The recommended 
volumes are on the RTOG website under the “Core Lab/Contouring Atlases” menu 
(http://www.rtog.org/CoreLab/ContouringAtlases/ProstatePelvicLymphNodes.aspx).
The CTV is described as being 7 mm around the iliac vessels, carving out bowel, bladder and 
bone, which translates into just contouring the iliac/obturator areas with essentially no extra 
margin because of the proximity to these structures (this is well-illustrated in the contouring 
Atlas). Thus, the PTV margins described above are the margins that venture into the potential 
bowel space, bladder and bone. The remainder of the CTV1, including the prostate bed and 
seminal vesicle bed are as described above. The CTV2 will include the prostate bed ( 64.8-70.2 
Gy), as described for PBRT above. The PTV1 and PTV2 margins should be a minimum of 0.8 


25
cm in all dimensions. A reduction of the PTV margin from 0.8 cm to ≥ 0.6 cm to minimize rectal 
exposure will be considered an acceptable variation. A posterior margin of < 0.6 cm will be 
considered an unacceptable deviation. The maximum dose in the PTV2 (the PTV1 is expected 
to have greater heterogeneity and no specific constraints are given) above the prescribed dose 
will be 7%; an acceptable variation will be > 7% to ≤ 12% and an unacceptable deviation >12%. 
The planned dose of 64.8-70.2 Gy will be declared after the patient is planned and all dosimetric 
parameters finalized A minimum of four treatment fields should be used. The normal tissue 
outlines will be the same as described above, with the added contouring of the potential space 
for small/large bowel in the pelvis. The potential bowel space will include the space on either 
side of the bladder to the medial edge of the lymph node outline laterally, beginning 
approximately at the top of the prostate bed field to one CT axial imaging level above the most 
superior level displaying a CTV1 contour. Care should be taken to avoid the presacral lymph 
node region in the bowel volume.
No specific field arrangement is required, although typically 5-9 fields are used. Rotational IMRT 
treatments are permitted, as long as the constraints are met. The posterior PTV margin at the 
bladder neck-rectum interface should not include the entire width of the rectum. A composite 
plan should be generated showing that at least 95% of the PTV1 and PTV2 receive the 
prescribed dose; a variation acceptable will be noted if < 95% to 90% of the PTV receives the 
prescribed dose, and a deviation unacceptable will be noted if < 90% of the PTV receives the 
prescribed dose. The maximum dose within the PTV2 (the PTV1 is expected to have greater 
heterogeneity and no specific constraints are given), above the prescribed dose, will be 15%; an 
acceptable variation will be > 15% to ≤ 20% and an unacceptable deviation > 20%. The other 
dosimetric parameters for IMRT are the same as for PBRT, except for the addition of a small 
bowel constraint.
Small/Large Bowel: The volume to be contoured is described above. For the patients receiving 
PLNRT, ≤ 150 cc of potential bowel space should receive ≥ 45 Gy. A variation will be noted if > 
150 cc to 200 cc of potential small bowel space receives ≥ 45 Gy. A secondary variation will be 
noted if >200 cc receives >45 Gy (see below). Since there are not protocol violations for bowel, 
treatment volumes should not be dramatically altered to adjust for bowel. In prior protocols, 
considerable bowel was in the field and patients tolerated treatment well. Thus, these 
constraints act as a guide.
Overlap of the Bowel with the Prostate Bed PTV: This situation has been one of concern in 
cases where the high dose PTV overlaps with loops of bowel. Since these patients have had 
prior surgery, bowel is not as mobile as for the patient with an intact prostate. However, it should 
be kept in mind that such compromises were not done in prior studies and that this should be an 
infrequent occurrence.
Overlap of the Bowel with the Lymph Node PTV: No adjustments in the PTV are permitted. 
Since the potential bowel contour abuts the lymph node CTV, there should be an overlap with 
the lymph node PTV. The overlap is expected.
Use of cone beam CT and plan adjustment: There may be cases in which the target and 
surrounding normal tissues are found to not be reproducible relative to the simulation CT and 
consequent plan. It should be emphasized that replanning should be avoided if at all possible 
because this will be considered a deviation. If the patient must be replanned in the opinion of 
the treating physician, then a deviation will be recorded, but continue to treat the patient per 
protocol in terms of dose and CTV/PTV volumes.


26
7.5.4.2.2 Pelvic Lymph Node Radiotherapy (PLNRT) planning – Arm B
For patients on Arm B, the Pelvic Lymph Node Radiotherapy clinical target volumes CTV1 & 
CTV2 as defined in 7.5.4.2.1 above will be contoured and submitted to the Emory Radiation 
Oncology Department. The Radiation Oncology PI (Dr. Jani) will supervise registration of the 
FACBC scan with the planning CT scan for definition of the pelvic lymph node and prostate bed 
CTV’s (CTV1/CTV2) which will in each case be defined as the union of the CTV1/CTV2 in 
section 7.5.5 above with the prostate bed uptake seen on the FACBC scan. PTV expansions 
around this final CTV1/CTV2 will be as in section 7.5.4.2.1 above.
7.5.4.2.3 Critical Structures – Arm A or Arm B
The critical normal structures are the bladder, rectum, small/large bowel above the rectum, and 
femoral heads. The normal tissues will be contoured and considered as solid organs.
The bladder should be contoured from its base to the dome, excluding the CTV1 (the CTV1 
includes the bladder neck).
The rectum should be contoured from the anus (at the level of the ischial tuberosities) to the 
rectosigmoid flexure (this is roughly at about 10 cm) or for a maximum length of 15 cm if the 
sigmoid flexure is felt to be higher.
Each femoral head should be outlined down to the interface between the greater and lesser 
trochanters. Each femoral head should be considered separately.
For the patients who will undergo PLNRT treatment, the external iliac, obturator, internal iliac 
and common iliac vessels/lymph node regions should be outlined inferiorly from where the 
external iliacs become the inguinal vessels and superiorly from the level of the common iliacs at 
L5-S1. The presacral lymph nodes from L5-S1 to S3 should be included.
For the patients who will undergo PLNRT treatment in, the potential bowel space (not individual 
loops of bowel) where the small and large bowel may fall should be outlined. The borders are 
the abdominal wall anteriorly, pelvic sidewalls laterally (excluding the pelvic lymph node 
regions), superiorly to one cut above the last axial CT image on which the lymph nodes are 
outlined and inferiorly from the level of the top of CTV1 (outlining around the sides of the 
bladder near the top of the bladder to encompass the bowel that may fall into these regions). 
Posteriorly, the small bowel potential space should extend to in front of the sacrum, abutting the 
anterior presacral nodal contours.
The tissue within the skin and outside all other critical normal structures and PTV’s is 
designated as unspecified tissue. 
7.5.5 Documentation Requirements 
The Radiation Oncology PI (Dr. Jani) will facilitate the review of the CTV, PTV, and designated 
organs at risk (critical structures). For patients on Arm B of the protocol, the PTV ultimately used 
to treat the patient (which includes information from the FACBC/planning CT registration) will be 
sent back securely to the treating institution. For both arms, the planning CT images, target 
volume structure set, and treatment plan ultimately used to treat the patient will be stored 
securely on the Emory Radiation Oncology server. 


27
The treating institution will archive treatment prescription and verification images for later review 
by the study chair if requested. At least one port film from each orthogonal film along with the 
digital reconstructed radiographs (DRRs) from the treatment planning program shall be acquired 
and kept for evaluation. Note: Images are required to be taken but not submitted.
7.5.6 Compliance Criteria
 
7.5.6.1 Dose Heterogeneity
The maximum dose within the PTV, above the prescribed dose, will be 15%; an acceptable 
variation will be > 15% to ≤ 20% and an unacceptable deviation > 20%. Although, the maximum 
dose allowable in the PTV(s) will be 15% above the prescribed dose, it is possible in the vast 
majority of cases to achieve less than 15%.
7.5.6.2 Normal Tissue Deviations
Less than or equal to 35% and 55% of the rectum should receive ≥ 65 Gy and ≥ 40 Gy, 
respectively. Less than or equal to 50% and 70% of the bladder minus prostate bed CTV 
(Bladder - CTV) should receive ≥ 65 Gy and ≥ 40 Gy, respectively. The criteria for the bladder 
are relaxed because the dosimetric relationship of volume exposed to the specified marker 
doses is much less clear and the bladder neck is included in the CTV. Less than or equal to 
10% of each femoral head should receive ≥ 50 Gy. A variation acceptable will be noted if up to 
an additional 5.0% of either the femoral head receives > 50 Gy. For the patients receiving 
PLNRT, ≤ 150 cc of potential small/large bowel space should receive ≥ 45 Gy. A primary 
variation will be noted if > 150 cc to 200 cc of potential small/large bowel space receives ≥ 45 
Gy. A secondary variation will be noted if > 200 cc of potential small/large bowel space receives 
≥ 45 Gy.
7.5.6.3 Radiotherapy Quality Assurance Reviews 
The Radiation Oncology PI (Dr. Jani) will facilitate the review of CTV, PTV, designated organs 
at risk, isodose distributions, treatment plans, and dose-volume histograms (DVH’s) of interest 
for each study subject prior to initiation of radiotherapy. 
Specifically the following structures and DVH’s will be reviewed and archived on the secure 
Emory Radiation Oncology server (below are suggested standard names for the structures): 
For all patients: 
Bladder
Rectum
Small Bowel
Penile_Bulb
R_Femoral_Head
L_Femoral_Head
For Prostate Bed only patients: 
CTV
PTV
For Pelvic radiotherapy patients:
Pelvic_Lymph_Nodes
CTV1
CTV2


28
PTV1
PTV2
Additionally, for Arm B only (final volumes including FACBC information registered to 
planning CT scan): 
For Prostate Bed only patients: 
CTV_final
PTV_final
For Pelvic radiotherapy patients:
Pelvic_Lymph_Nodes_final
CTV1_final
CTV2_final
PTV1_final
PTV2_final
7.5.6.4 Radiation Adverse Events
All patients will be seen weekly by their radiation oncologist during radiation therapy. Any 
observations regarding radiation reactions will be recorded and should include attention toward 
the following potential side effects:
Small bowel or rectal irritation manifesting as abdominal cramping, diarrhea, rectal urgency, 
proctitis, or hematochezia;
Bladder complications including urinary frequency/urgency, dysuria, hematuria, urinary tract 
infection, and incontinence; 
Radiation dermatitis.
Clinical discretion may be exercised to treat side effects from radiation therapy as described 
above. Examples of typical medications used in the management of rectal side effects, such as 
diarrhea, include diphenoxylate or loperamide. Bladder or rectal spasms are usually treated with 
anticholinergic agents or tolterodine. Bladder irritation may be managed with phenazopyridine. 
Erectile dysfunction is often treated with medical management or mechanical devices.


29
8.0 Patient Assessments
8.1 Prior to Randomization
History and Physical (i.e., symptom-directed examination)
ECOG/Zubrod Performance Status (see Appendix 1)
Pathology report (from radical prostatectomy)
Bone scan report
CT or MRI pelvis report
PSA
EPIC sheet (see Appendix 2)
Pre-FACBC Radiotherapy Decision / Attestation Sheet (see Appendix 3)
8.2 After Randomization but before Radiotherapy
Digital Rectal Examination (DRE) [may also be done prior to randomization]
If randomized to Arm A:
CT simulation
Radiotherapy Treatment Planning
If randomized to Arm B: 
FACBC scan (& related lab tests)
CT simulation
Radiotherapy Treatment Planning
8.3 During Radiotherapy
Adverse event evaluations (see Appendix 4 for AE definitions) on average once weekly during 
XRT course
8.4 After Radiotherapy
Note: see Appendix 4 for all radiotherapy adverse event definitions, and see Appendix 5 for the 
Follow-up Data Sheet. 
1 month (+/- 2 weeks) follow-up: 
Zubrod PS, PSA, AST/ALT/Serum Testosterone (if on hormones), 
EPIC, adverse event evaluation
6, 12, 18, 24, 30, and 36 month (+/- one month) follow-ups: 
Zubrod PS, DRE, PSA, AST/ALT/Testosterone (if on hormones), EPIC, adverse event 
evaluation; Radiological workup (CT/MR scan, Bone scan, etc.) as clinically indicated
>36 month (+/- two months) follow-up:
As per clinical routine
Note that if primary endpoint is reached (i.e., 36 months of follow-up is reached, patient is 
determined to fail treatment [as defined in section 6.5], or the decision to administer 
radiotherapy is aborted), subsequent follow-up (and specified data collection at the above 
timepoints) is optional. Also, if subject declines to follow-up after reasonable attempt has been 


30
made to contact the subject, data through the most recent follow-up will be used for the primary 
and secondary endpoints of the study. 
For synopsis of study assessments, see Appendix 9.0. Statistical Analysis
Statistical considerations for Specific Aim 1:
Primary endpoint: 
As the primary analysis, the chi-square test will be first used to compare the 3 year biochemical 
failure rates between the two arms. Then a survival analysis will be conducted on biochemical 
failure time. The survivor functions for biochemical failure will be estimated with Kaplan and 
Meier method and plotted in a graph. The logrank test will be used to test the difference in the 
biochemical failure between the two arms. The power and sample size calculation is based on 
the difference in the 3 year biochemical failure rates between the two arms. We estimate that 
the 3 year biochemical control rates are 50% and 70% for the Arm A and Arm B, respectively. 
The 50% rate with conventional imaging (Arm A) has been reported in all salvage patients 
treated with a median PSA of 2.0 ng/mL(14-16, 21-23). The estimated improvement in 
biochemical failure (in Arm B) comes from the sensitivity data from the preliminary results of Aim 
1 below (an estimated 25/46 (54%) true positive rate [see Table 1 in the “Preliminary Data for 
Specific Aim 1” subsection] would be expected to translate conservatively into a failure rate 
difference of 20% advantage in biochemical control at 3 years (over those treated without the 
aid of anti-3-[18F]FACBC guidance). In the study, a total of 162 patients will be accrued and 
randomized to the two groups (Arm A and Arm B) with a ratio of 1:1. At the significance level of 
0.05, the sample size of 73 patients per group will achieve a power of at least 80% to detect the 
difference (50% vs 70%) between the two groups using chi-square test.   
Secondary endpoints: 
PSA Analysis: Although stratification during enrollment will be done by PSA < 2.0 or  PSA ≥ 2.0, 
during analysis, cohorts in arms A and B will be stratified by PSA <0.2; ≥0.2 and <1.0; ≥1.0 and 
<2.0; ≥2.0 and <5.0, ≥5.0 and <10.0, ≥10 ng/mL. We will continuously monitor the accrual to 
ensure enough patients in each strata (as was done in the prior RO1 trial); also, no more than 
50% of patients in each arm will have PSA < 2.0 – this will ensure that enough high-risk patients 
are included. Stratification groups may be conglomerated or subdivided to achieve adequate 
statistical power depending on accrual figures. This will allow us to determine (a) whether 
patients with high PSA (a population with a relatively low chance of success with radiotherapy) 
can be controlled with radiotherapy guided by anti-3-[18F]FACBC, and (b) whether for a given 
PSA level (in each individual or combined strata) whether anti-3-[18F]FACBC guided 
radiotherapy improves biochemical control. Patients will also be analyzed per risk level 
stratification groups as above; this analysis will serve as the basis for design of a larger trial in 
the future which more closely examines the strata. 
Multivariate Analysis: For the multivariate analysis of biochemical failure time, a Cox model will 
be employed to assess the effect of anti-3-[18F]FACBC guided treatment on biochemical failure 
time after adjusting for patients’ other demographic and clinical factors. To confirm that the use 
of anti-3-[18F]FACBC PET-CT permits the selection of patients with high PSA levels who would 
not ordinarily be treated with radiotherapy, a chi-square test will also be conducted to compare 
frequency of patients with high PSA levels between the two arms. 
Toxicity Analysis: Common Terminology Criteria for Adverse Events (CTCAE) [acute and late] 
gastrointestinal (GI) and [acute and late] genitourinary (GU) toxicity rates will be charted and 
EPIC scores (for GU, GI, and Sexual axes, in addition to total scores) for arms A and B and 
compared. Additionally, a multivariate analysis will be done examining all patient demographic, 
disease, and treatment factors (including anti-3-[18F]FACBC use) that influence each of these 


31
toxicity endpoints. This will enable determining whether anti-3-[18F]FACBC PET-CT guided 
treatment is tolerable compared to conventional treatment. For provider-reported toxicity, the 
Chi-square test will be conducted to compare the distribution of the grade (0, 1, 2, or 3) of acute 
GU or GI toxicity between the two arms, respectively. For the multivariate analysis of acute GU 
or GI toxicity, an ordered logistic model will be employed to assess the effect of anti-3-
[18F]FACBC guided treatment on the grade of acute GU or GI toxicity after adjusting for patients’ 
other demographic and clinical factors. A survival analysis will be conducted on late GU or GI 
toxicity. The survivor functions for the time to late GU or GI toxicity (grade ≥2) will be estimated 
by Kaplan and Meier method and plotted in a graph. The logrank test will be used to test the 
difference in the overall time to late GU or GI toxicity between the two arms. For the multivariate 
analysis of late GU or GI toxicity, a Cox model will be employed to assess the effect of anti-3-
[18F]FACBC guided treatment on the time to late GU or GI after adjusting for patients’ other 
demographic and clinical factors.For patient-reported toxicity, a similar analyses to that 
described above will be done using EPIC scores rather than CTCAE grades. 
Analysis of Treatment Decisions Data
For Specific Aim 2, we will analyze patients treated in Arm B (of the randomized trial in Specific 
Aim 1 above) and compare initial (pre- anti-3-[18F]FACBC) versus final (post- anti-3-[18F]FACBC) 
treatment decisions regarding (a) the decision of whether to offer post-prostatectomy 
radiotherapy, (b) the decision of whether to treat the pelvic lymph nodes in addition to the 
prostate bed. We will also explore the cost-effectiveness of anti-3-[18F]FACBC (and anti-3-
[18F]FACBC PET-CT based decision changes) in guiding post-prostatectomy treatment. 
In determining the impact of anti-3-[18F]FACBC PET-CT on the decision to offer 
radiotherapy, as shown in the schema of the randomized trial for Specific Aim 1 above, the 
radiotherapy treatment decision will be charted before the anti-3-[18F]FACBC is completed. 
Then, the final decision based on the anti-3-[18F]FACBC PET-CT will also be charted as 
determined by the strict protocol-defined use of anti-3-[18F]FACBC. Then, the total number of 
decision changes (changes from offering radiotherapy to not, and not offering to offering 
radiotherapy) will be noted and compared. Similarly, in determining the impact of anti-3-
[18F]FACBC on the decision to treat pelvic lymph nodes (versus prostate bed alone), as shown 
in the schema of the randomized trial for Specific Aim 1 above, the radiotherapy treatment field 
decision will be charted before the anti-3-[18F]FACBC PET-CT is done. Then, the final treatment 
field decision based on the anti-3-[18F]FACBC will also be charted as determined by the strict 
protocol-defined use of anti-3-[18F]FACBC. Then, the total number of decision changes 
(changes to treating regionally to include the pelvic nodes, and changes to treating the prostate 
fossa alone) will be noted and compared. In addition to the individual decisions regarding the 
decision to treat and the region to treat, these decisions will be examined (weighing each 
decision change equally) in composite to determine the total number of decision changes and 
the overall impact of anti-3-[18F]FACBC PET-CT on decision-making. 
Analysis of Data for Cost Effectiveness
A cost-effectiveness analysis based on these decision changes will also be done. As anti-3-
[18F]FACBC is used to guide decision making, the simple cost of anti-3-[18F]FACBC PET-CT is 
not the only item under consideration, as the employment of anti-3-[18F]FACBC can guide the 
decision on whether to offer radiotherapy and may influence the biochemical control rate and 
need for salvage (hormone) therapy. The two major factors that will influence the overall cost of 
treatment when using anti-3-[18F]FACBC are the number of decision changes to offer versus not 
offer radiotherapy (and resultant salvage hormone therapy), and the biochemical failure rate 
difference (Arm B versus Arm A in the randomized trial). 
Estimates will be made for (a) the cost of radiotherapy, (b) the cost of hormone therapy, 
and (c) the cost of anti-3-[18F]FACBC. A model will be constructed which assumes (a) failures 


32
are treated with hormone therapy, (b) decisions to abort radiotherapy imply using hormone 
therapy. In this manner the cost-effectiveness of anti-3-[18F]FACBC for post-radical 
prostatectomy radiotherapy can be determined. Avoiding futile radiotherapy will also be factored 
into the data analysis as cost-saving.
Statistical considerations for Specific Aim 2: 
The McNemar test will be used to compare (a) the decision to offer radiotherapy or not and (b) 
the decision on treatment of pelvic nodes or not between the initial (pre- anti-3-[18F]FACBC) and 
final (post- anti-3-[18F]FACBC) treatment decisions, respectively. The Stuart-Maxwell test will be 
also used to compare the combined number of decision changes for both decisions together 
between the initial (pre- anti-3-[18F]FACBC) and final (post- anti-3-[18F]FACBC) treatment 
decisions. The cost-effectiveness of anti-3-[18F]FACBC (and anti-3-[18F]FACBC based decision 
changes) in guiding post-prostatectomy treatment will be further explored by comparing the cost 
of radiotherapy, the cost of hormone therapy, and the cost of anti-3-[18F]FACBC PET-CT with t-
test.  
Statistical Considerations for Specific Aim 3: 
Paired t-test will be used to compare the target volumes (CTV and PTV) and the planned dose 
delivered to surrounding bladder, rectum, and penile bulb between the initial (pre- anti-3-
[18F]FACBC) and final (post- anti-3-[18F]FACBC) radiation treatment plans. Spearman’s 
correlation coefficient will be estimated to measure the correlations of the bladder and rectum 
dosimetric endpoints (V65, V40) with the grades (0, 1, 2, or 3) of acute GU or GI toxicity, 
respectively, and Wald test will be used to test the significance level of their correlations. A COX 
model will be employed to assess the relationship between the time to late GU or GI toxicity 
(grade ≥2) and the bladder and rectum dosimetric endpoints (V65, V40), respectively. 
For this technically-oriented aim, we will analyze patients treated in Arm B (of the randomized 
trial in Specific Aim 1 above) and compare initial (pre- anti-3-[18F]FACBC PET-CT) versus final 
(post- anti-3-[18F]FACBC PET-CT) radiation treatment plans. We will determine the impact of 
anti-3-[18F]FACBC PET-CT on (a) target volumes – the clinical target volume (CTV) and 
planning target volume (PTV), and (b) the planned dose delivered to surrounding normal 
structures (bladder, rectum, and penile bulb).
Prostate bed CTV (CTV-pre) will first be defined by CT without any anti-3-[18F]FACBC 
PET-CT information – this will enable blinding of the anti-3-[18F]FACBC PET-CT information 
when first designing the treatment plan. Then the anti-3-[18F]FACBC PET-CT scan [using iso-
SUV level of 2.2 (55)] will be registered to the planning CT scan using deformable registration to 
define the final CTV used for treatment planning (CTV-post) [see proposed details of this 
registration under “Preliminary Data for Specific Aim 3” subsection below]. CTV-pre and CTV-
post will be compared, as will (using standard expansion from CTV to planning target volume 
[PTV] in both arms) PTV-pre and PTV-post. In the above manner the impact of anti-3-
[18F]FACBC PET-CT in influencing target volumes can be determined. 
CTV-pre will be expanded using uniform guidelines to define PTV-pre. CTV-post will be 
expanded to define PTV-post. For each patient 2 plans will be generated – one using PTV-pre 
and a second using PTV-post. Dose volume histograms for the normal structures (rectum, 
bladder, and penile bulb) using standard dosimetric endpoints (V65 [%volume receiving ≥ 65 
Gy], V40) and compared (51, 52). Additionally, the bladder and rectum dosimetric endpoints will 
be correlated with observed rates of GU and GI toxicity (which are both components of the 
clinical outcomes study in Specific Aim 1 above), respectively. 


33


34
10.0 Adverse Event Reporting:
Adverse event data collection and reporting, which are required as part of every clinical trial , 
are done to ensure the safety of patients enrolled in the studies as well as those who will enroll 
in future studies using similar agents. Adverse events are reported in a routine manner at 
scheduled times during a trial (please follow directions for routine reporting provided in the full 
Data Safety and Monitoring Plan). Additionally, certain adverse events must be reported in an 
expedited manner to for timelier monitoring of patient safety and care. The following sections 
provide information about expedited reporting.
Serious adverse event (SAE) or reaction is any untoward medical occurrence related to the 
imaging analysis that: results in death, is life-threatening, requires inpatient hospitalization or 
prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or 
is a congenital anomaly / birth defect.
The definition of serious adverse event (experience) also includes important medical event. 
Medical and scientific judgment should be exercised in deciding whether expedited reporting is 
appropriate in other situations, such as important medical events that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the patient or may require 
intervention to prevent one of the other outcomes listed in the definition above. These should 
also usually be considered serious. Examples of such events are intensive treatment in an 
emergency room or at home for allergic bronchospasm; blood dyscrasias or convulsions that do 
not result in hospitalization; or development of drug dependency or drug abuse.
Attribution:  The determination of whether an adverse event is related to a study imaging agent.  
The categories are:
Definite:  The adverse event is clearly related to the study imaging agent.
Probable:  The adverse event is likely related to the study imaging agent.
Possible:  The adverse event may be related to the study imaging agent.
Unlikely:  The adverse event is doubtfully related to the study imaging agent.
Unrelated:  The adverse event is clearly not related to the study imaging agent.
Unexpected Adverse Event:  An adverse event, the nature or severity of which is not consistent 
with the applicable product information.  
Investigational Agent:  A protocol drug administered under an Investigational New Drug 
Application (IND).  In this case, this will be FACBC.
Commercial Agent:  An agent not provided under an IND but obtained from a commercial 
source.
Determination of Reporting Requirements
Reporting requirements may include the following considerations: 1) whether the patient has 
received an investigational or commercial agent; 2) the characteristics of the adverse event 


35
including the grade (severity), the relationship to the study imaging agent (attribution), and the 
prior experience (expectedness) of the adverse event; 3) the Phase (1, 2, or 3) of the trial; and 
4) whether or not hospitalization or prolongation of hospitalization was associated with the 
event.
Steps to determine if an adverse event is to be reported in an expedited manner:
Step 1: Identify the type of event using the NCI Common Toxicity Criteria for Adverse Event 
Reporting Version 4.0 (CTCAE v4.0). The CTCAE v4.0 provides descriptive terminology and a 
grading scale for each adverse event listed. A copy of the CTCAE v4.0 can be downloaded from 
the CTEP home page (http://ctep.cancer.gov). Additionally, if assistance is needed, the NCl 
has an Index to the CTCAE v4.0 that provides help for classifying and locating terms. All 
appropriate treatment locations should have access to a copy of the CTCAE v4.0.
Step 2: Grade the event using the NCI CTCAE  v4.0.
Step 3: Determine whether the adverse event is related to the protocol imaging agent 
(investigational or commercial). Attribution categories are as follows:  Unrelated, Unlikely, 
Possible, Probable, and Definite.
Step 4: Determine the prior experience of the adverse event. Expected events are those that 
have been previously identified as resulting from administration of the agent. An adverse event 
is considered unexpected, for expedited reporting purposes only, when either the type of event 
or the severity of the event is not listed in the investigator brochure for an investigational agent 
or the drug package insert for a commercial agent.
Step 5: Review Table 1 below to determine if there are any protocol-specific requirements for 
expedited reporting of specific adverse events that require special monitoring.
Step 6: Determine if the protocol treatment given prior to the adverse event included 
investigational agent(s), a commercial agent(s), or a combination of investigational and 
commercial agents.
Reporting Methods:
The Principal Investigator is responsible for evaluating all reports of adverse events which occur 
in patients enrolled on this study and reporting those events which are serious to the FDA, and 
the Emory University IRB according to the guidelines below. SAEs must be reported as required 
by the WCI DSMP.
Expedited reporting requirements:  All grade 4-5 adverse events (unexpected and expected) 
and grade 2-3 adverse events that are unexpected must be reported to Principal Investigator via 
the AE Form within 24 hours of occurrence.
Routine reporting requirements:  All adverse events must be reported via the Toxicity Form and 
submitted according to the bodies outlined below.  


36
Table 1. Outline of Reporting Documents to be Used:
a All deaths within 30 days of the last dose of treatment with an investigational agent regardless 
of attribution; and any late death attributed to the agent (possible, probable or definite), should 
be reported within 10 working days.  
b Submit to Emory within 24 hours of occurrence.
c See submission schedule in Section 11.0.
Reporting to Institutional Review Board (IRB):  All SAEs must be reported by the Principal 
Investigator to the Emory University IRB as required by their regulations and the conditions of 
approval for the protocol.
Reporting to FDA: The Principal Investigator must notify the FDA in a written IND safety report 
of any adverse event which is both serious and unexpected.  Each written notification must be 
made as soon as possible but no later than 15 calendar days of first becoming aware of the 
event.  Reports should be submitted using the FDA Form 3500A (available on the FDA website 
at www.fda.gov/medwatch.  Reporting may be done online or via mail or fax.     
Any unexpected fatal (Grade 5) or unexpected, life-threatening (Grade 4) adverse event must 
be reported to the FDA as soon as possible but no later than 7 calendar days of first becoming 
aware of the event. Reports should be submitted using the FDA Form 3500A via fax at 1-800-
332-0178
Grade 2
Grade 3
Grade 4
Grade 5a
Report to
Unexpected
Expected
Unexpected
Expected
Unexpected
Expected
Unexpected
Expected
Principal 
Investigator
AE Formb
Toxicity 
Formc
Toxicity 
Formc
AE Formb
Toxicity 
Formc
Toxicity 
Formc
AE Formb
Toxicity 
Formc
AE 
Formc
Toxicity 
Formc
AE Formb
Toxicity 
Formc
AE 
Formb
Toxicity 
Formc


37
11.0 Data Safety Monitoring Plan
The Data and Safety Monitoring Committee (DSMC) of the Winship Cancer Institute will oversee 
the conduct of this study. This committee will review all pertinent aspects of study conduct 
including patient safety, compliance with protocol, data collection and efficacy. The committee 
will review the charts of 10% of patients enrolled to the study and two of the first 5 patients 
entered to the study. Reviews will occur annually for studies that are low risk or moderate risk. 
High risk studies will be reviewed every 6 months. The committee reserves the right to conduct 
additional audits if necessary at any time-point. The Principal Investigator is responsible for 
notifying the DSMC about the accrual of patients when the first 5 have been entered to the 
study. The PI will also notify the DSMC of the study status within 2 months before the next 
annual review is due. The charter for the Winship DSMC is available upon request to the 
investigator or other study-related personnel.
Additionally, the study team [to include the PI (Dr. Jani) & NIH grant co-PI (Dr. Schuster)] will 
present all data analyzed to date, record of accrual, and attributable toxicities at the 
Multidisciplinary Genitourinary Oncology meeting which meets on a monthly basis (and is 
chaired by Dr. Omer Kucuk). This body will serve as the DSMC for study sites that are external 
to Emory,  and will produce a written document every 6 months in which the decision to proceed 
or to halt the study will be made based upon standard clinical and scientific standards.


38
12.0  References
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Lange PH. PROSTASCINT scan for staging prostate cancer. Urology. 2001;57(3):402-
6.PMID=11248606.


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33.
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postprostatectomy biochemical failure: does pretreatment radioimmunoscintigraphy help select 
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21.PMID=18234446.
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for characterization of pelvic lymph nodes in patients with prostate cancer by diffusion-weighted 
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42
66.
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43
13.0 Appendices
Appendix 1: ECOG/Zubrod Performance Scale
Appendix 2: EPIC
Appendix 3: Pre-FACBC Radiotherapy Decision Sheet
Appendix 4: RTOG/CTCAE Toxicity Grading
Appendix 5: Follow-up Data Sheet
Appendix 6: Study Parameters Table


44
Appendix 1:
ECOG/ ZUBROD PERFORMANCE SCALE
0 - Fully active, able to carry on all predisease activities without restriction
1 - Restricted in physically strenuous activity but ambulatory and able to carry
work of a light or sedentary nature. For example, light housework, office
work
2 - Ambulatory and capable of all self-care but unable to carry out any work
activities. Up and about more than 50% of waking hours
3 - Capable of only limited self-care, confined to bed or chair 50% or more of
waking hours
4 - Completely disabled. Cannot carry on self-care. Totally confined to bed
5 - Death


45
Appendix 2: 
Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) 
Questionnaire.
Firm enough for masturbation 
and foreplay only
Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP)
Patients: Please answer the following questions by checking the appropriate checkbox.  All questions are 
about your health and symptoms in the LAST FOUR WEEKS.  Select one answer for each question.  
2. Which of the following best describes your urinary control?  
0      Total control      1      Occasional dribbling      2    Frequent dribbling      4      No urinary control
3. How many pads or adult diapers per day have you been using for urinary leakage?  
0      None        1      One pad per day        2      Two pads per day        4      Three or more pads per day
4. How big a problem, if any, has urinary dripping or leakage been for you?  
0      No problem     1     Very small problem     2      Small problem     3      Moderate problem      4      Big problem
CLINICIANS: ADD the answers from questions 2-4 to calculate 
the Urinary Incontinence Symptom Score (out of 12):
5. How big a problem, if any, has each
of the following been for you?
a. Pain or burning with urination
b. Weak urine stream/incomplete bladder emptying
c. Need to urinate frequently
0                   1                    2                  3  
4
No 
problem
Very small 
problem
Small 
problem
Moderate 
problem
Big 
problem
CLINICIANS: ADD the answers from questions 5a-5c to calculate the 
Urinary Irritation/Obstruction Symptom Score (out of 12):
6. How big a problem, if any, has each
of the following been for you?  
a. Rectal pain or urgency of bowel movements
b. Increased frequency of your bowel movements
c. Overall problems with your bowel habits
CLINICIANS: ADD the answers from questions 6a-6c
to calculate the Bowel Symptom Score (out of 12):
7. How would you rate your ability to reach orgasm (climax)?  
8. How would you describe the usual quality of your erections?  
0                                       1                    
2               
4       None at all
Firm enough 
for intercourse
Not firm enough for 
any sexual activity
9. Overall, how much of a problem has your sexual function or lack of sexual function been for you?  
CLINICIANS: ADD the answers from questions 7-9 to 
calculate the Sexual Symptom Score (out of 12):
10. How big a problem, if any, has each
of the following been for you?  
a. Hot flashes or breast tenderness/enlargement
b. Feeling depressed
c. Lack of energy
CLINICIANS: ADD the answers from questions 10a-10c to calculate 
the Vitality/Hormonal Symptom Score (out of 12):
0      No problem     1     Very small problem     2      Small problem     3      Moderate problem      4      Big problem
A Clinical Tool to Measure Urinary, Bowel, Sexual and Vitality/Hormonal Health                Date: ___ /___ /___
0      Very good            1      Good            2      Fair            3      Poor            4      Very poor to none
0                   1                    2                  3  
4
0                   1                    2                  3  
4
0                   1                    2                  3  
4
No 
problem
Very small 
problem
Small 
problem
Moderate 
problem
Big 
problem
0                   1                    2                  3  
4
0                   1                    2                  3  
4
0                   1                    2                  3  
4
No 
problem
Very small 
problem
Small 
problem
Moderate 
problem
Big 
problem
0                   1                    2                  3  
4
0                   1                    2                  3  
4
CLINICIANS: Add the five domain summary scores to calculate the Overall Prostate Cancer QOL Score (out of 60):
1. Overall, how much of a problem has your urinary function been for you?  
No problem                Very small problem         
Small problem               Moderate problem             Big problem


46
Appendix 3:
Pre-FACBC Radiotherapy Decision / Attestation Sheet
Note: This form must be completed prior to randomization.
Pathologic Stage:       T_______ N________
M_________
Margin positive (y/n)_____        Extra-capsular Extension (y/n) ______    Seminal Vesical 
Invasion(y/n)_____
Highest post-prostatectomy PSA:    Value________
Date________
Most recent PSA:    Value________
Date________
DRE date & Findings___________
CT or MRI scan shows no extrapelvic disease (y/n)______________
Scan date___________
Bone scan shows no skeletal metastases (y/n)_____________
Scan date___________
Please answer the below provider-related questions:
1. Are you planning to offer the patient pelvic radiotherapy (check only one):   Yes_____
No/Undecided______
     If Yes, which of the following general target volumes are you planning to treat (check only one): 
Prostate bed alone _______
OR 
Prostate bed plus regional lymph nodes ____
     If No/Undecided, please provide reason below: 
Wish to observe PSA 
______
Likely futile________
Other (please explain): _________________________________________________


47
2. Are you planning to offer the patient androgen deprivation therapy?     Yes_____
No______
If Yes, what is intended duration ?________________
3. All other pretreatment evaluations ( Symptom-directed Exam, Zubrod, path report, bone scan report, 
CT/MR report, PSA, EPIC, [LFT’s/testosterone only if hormones intended]) have been completed:
    
 Yes______
No_______
If no, please explain__________________________
Provider signature____________________________________
Date_____________


48
Appendix 4:
RTOG/CTCAE Definitions
CTCAE version 4.0 can be found at the following link: 
http://www.acrin.org/Portals/0/Administration/Regulatory/CTCAE_4.02_2009-09-
15_QuickReference_5x7.pdf
The common side effects related to pelvic radiotherapy are gastrointestinal (pages 28-54 of the above 
PDF), and urinary (pages 147-152 of above PDF).


49
Appendix 5:  
Follow-up Data Sheet 
Note: This form must be provided at each of  1, 6, 12, 18, 24, 30, and 36 months post-radiotherapy.
Follow-up Visit
_____ months post-radiotherapy
______ Date
Symptom-directed examination completed
_____ (y/n)
DRE completed (not needed at 1 month follow-up)?
_____ (y/n)
 
If completed, is DRE Normal?
______ (y/n)
ECOG/Zubrod Performance Status (0-5) _____ 
PSA (ng/mL):  
Value________
Date________
GU Toxicity Grade  
_____ (0-4)
GI Toxicity Grade 
 _____ (0-4)
Insert EPIC sheet here.
Other Toxicity? If so, list type(s) and 
grade(s)_____________________________________________________________
Did patient receive or is patient receiving androgen deprivation therapy ? ___(y/n)
If yes, below are needed (if androgen deprivation therapy spans current follow-up period): 
Testosterone: Value________
Date________ 
AST:
 
Value________
Date________
or ALT:  
Value________
Date________
Any evidence of clinical progression or started additional non-ADT systemic therapy since last visit ? 
_____ (y/n)
If clinical progression, provide details (CT scan, bone scan, biopsy, etc) including dates: 
 
__________________________________________________________________________________


50
If chemotherapy started, provide details of type and start 
date?_______________________________
Provider signature____________________________________
Date_____________


51
Appendix 6. Study Parameter Table [see also sections 8.1-8.4 for details]
During 
XRT
Follow-up After XRT
Long-
term 
follow 
up
Assessment
Pre-XRT  
(may be 
required 
for 
eligibility)
Weekly
1mo
6 mo
12 mo
18 mo
24 mo
30 mo
36 mo
As per 
routine
Symptom-
Directed 
Exam
x
x
x
x
x
x
x
x
x
x
DRE
x
x
x
x
x
x
x
x
Performance 
Status
x
x
x
x
x
x
x
x
x
Prostatectomy 
Report
x
PSA
x
x
x
x
x
x
x
x
x
Bone Scan
x
x
CT or MRI 
pelvis
x
x
EPIC
x
x
x
x
x
x
x
x
x
Radiotherapy 
Decision 
Sheet (RDS)
x
AST or ALT
If H 
intended
If on 
H
If on 
H
If on H
If on H
If on H
If on H
If on H
If on H
Serum 
Testosterone
If H 
intended
If on 
H
If on 
H
If on H
If on H
If on H
If on H
If on H
If on H
FACBC scan 
& related labs 
(only after 
RDS 
completed)
Arm B 
only
CT simulation
x
XRT plan 
registration
x


52
AE evaluation
x
x
x
x
x
x
x
x
x
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ICF_002.pdf: 
Study No.: «ID» 
Emory University IRB 
IRB use only 
Document Approved On: «ApproveDate» 
Page 1 of 12 
Version Date: 03/07/2018 
IRB Form 12152017 
Advanced Molecular Imaging with anti-3-[18F] FACBC PET-CT to Improve the Selection and Outcomes of Prostate 
Cancer Patients Receiving Post-prostatectomy Radiotherapy 
Informed Consent version date: March 07, 2018 
NCT01666808 


Study No.: «ID» 
Emory University IRB 
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Document Approved On: «ApproveDate» 
Page 2 of 12 
Version Date: 03/07/2018 
IRB Form 12152017 
Emory University, Saint Joseph’s Hospital, and Grady Health System 
Consent to be a Research Subject and HIPAA Authorization 
Title:   Advanced Molecular Imaging with anti-3-[18F] FACBC PET-CT to Improve the Selection and Outcomes of Prostate 
Cancer Patients Receiving Post-prostatectomy Radiotherapy 
Principal Investigator:  Ashesh B. Jani, MD, MSEE 
Study Supporter:  National Institute of Health 
Introduction:  
You are being asked to take part in this study because you have had surgery to remove your prostate and your study 
doctor has recommended radiation therapy because your blood level of Prostate Specific Antigen (PSA) has been going 
up. (The PSA is a value that helps determine the aggressiveness of your prostate cancer.) 
This form is designed to tell you everything you need to think about before you decide to consent (agree) to be in the 
study or not to be in the study.  It is entirely your choice.  If you decide to take part, you can change your mind later on 
and withdraw from the research study. The decision to join or not join the research study will not cause you to lose any 
medical benefits.  If you decide not to take part in this study, your doctor will continue to treat you. 
Before making your decision: 
•
Please carefully read this form or have it read to you
•
Please listen to the study doctor or study staff explain the study to you
•
Please ask questions about anything that is not clear
You can take a copy of this consent form, to keep. Feel free to take your time thinking about whether you would like to 
participate. You may wish to discuss your decision with family or friends. Do not sign this consent form unless you have 
had a chance to ask questions and get answers that make sense to you.  By signing this form you will not give up any 
legal rights. 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. law. This Web site 
will not include information that can identify you. At most the Web site will include a summary of the results. You may 
search this Web site at any time. 
Study Overview: 
The purpose of this study is to see if (1) using FACBC PET scan will be useful in helping your doctor plan your radiation 
treatments and (2) if, as a result of using the PET scan to plan your treatments, the outcome of radiation treatment will 
be improved. 


Study No.: «ID» 
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Page 3 of 12 
 
Version Date: 03/07/2018 
IRB Form 12152017 
FACBC is a radiotracer that is injected into the vein. After the substance is injected, scans called PET or Positron 
Emission Tomography are done. This is similar to having CAT scans or x-rays. In recent studies, FACBC has been 
shown to enter prostate cancer cells. FACBC has been approved by the FDA (Food and Drug Administration) for 
recurrent prostate cancer. 
External beam radiation therapy is one of the standard treatments for men with prostate cancer who have a rising 
PSA after surgery. Different methods of radiation therapy are used, and it is not known which one is best. Most 
commonly, the area where the prostate was originally located before being removed (the prostate bed) is treated, 
without treating the lymph nodes in the pelvis. Prostate cancer can spread to the lymph nodes. There is some 
evidence in men who have not had surgery that radiotherapy to the pelvic lymph nodes may stop the cancer from 
spreading under some conditions. Since treating the pelvic lymph nodes can result in increased side effects, the 
benefit of this method of radiation therapy needs to be tested. 
Procedures:  
You will need to have the following exams, tests or procedures to find out if you can be in the study. These exams, tests 
or procedures are part of regular cancer care and may be done even if you do not join the study. If you have had some 
of them recently, they may not need to be repeated. This will be up to your study doctor 
•
History and physical
•
A CT (Computed Tomography) scan or MRI (Magnetic Resonance Imaging) of your abdomen and pelvis to
determine if there is any evidence of cancer spread to the pelvic lymph nodes. A CT scan is a study using x-rays to
look at one part of your body. An MRI is imaging using a strong magnetic field to look at one part of your body.
•
A bone scan to determine if the cancer has spread to the bones.
•
Review of the tissue from your prior surgery to remove your prostate to determine your Gleason score (a value
that helps determine the aggressiveness of your prostate cancer).
•
You will be asked to complete a form that asks questions on your urinary, bowel hormone, and sexual functions.
You will be "randomized" into one of the study groups described below. Randomization means that you are put into a 
group by chance (like drawing straws). A computer program will place you in one of the study groups. You will be 
randomized to one of two groups of treatment. 
If you are in group 1 (often called "Arm 1"): You will receive radiation treatments to the prostate bed once daily, 5 
days a week, Monday through Friday, the exact number will be decided by your study doctor. Each radiation 
treatment will take about 15-30 minutes. 
If you are in group 2 (often called "Arm 2"):  
You will have a FACBC PET scan that will be used to plan your radiation treatment. 
On the day of the scan,  
•
You will be required to fast for 4hours before the scan.
•
You will be given oral contrast to drink; this allows the abdominal organs to be better visible.
FACBC scan: 
The scans will be performed at the Emory Center for PET located in the Nuclear Medicine Department on the first 
floor of the Emory University Hospital or in the Winship Cancer Institute. The entire procedure will last about 2 
hours, including set up and preparation time. Before the PET scan, you will be asked to not eat or drink for four 
hours. This will allow the FACBC to get in your blood system easier. You will meet with a technologist and doctor 
who are approved to work on this study, and who will be performing the procedures on you. An intravenous tube 
called a catheter (IV) will be inserted in a vein in your arm to be used later for injection of the FACBC. One hour 


Study No.: «ID» 
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Page 4 of 12 
Version Date: 03/07/2018 
IRB Form 12152017 
prior to scanning, you will drink 1 bottle (500 ml) of oral contrast over 1 hour to allow for better pictures of your 
abdomen and pelvic structures. 
After placement of the IV, you will lay down on a mobile couch that will slide into the scanner. The scanner has 
the appearance of a large box containing a large round opening into which your body is placed. An initial 
“transmission” scans lasting about 1 minute in which the couch will move. This transmission scan is similar to a 
CAT scan and is used to correct for the effect of your body on the PET scan in order to produce better images. This 
transmission scan is done on the PET scanner and will look no different to you. You will then receive a slow 
injection through the IV tube of the FACBC.  A set of PET scans (pictures) will be done over thirty minutes. The 
couch will move. When finished, the IV will be removed, and a urine specimen may be collected to test for how 
the body gets rid of the FACBC.  You will be able to leave the PET Center after this time. 
If you are medically eligible, depending on the results of your scan, you will receive radiation treatment to the prostate 
bed (and possibly, the pelvic lymph nodes) once daily, 5 days a week, Monday through Friday, the exact number of 
treatments and area to be treated will be decided by your study doctor. Each radiation treatment will take about 15-30 
minutes. Also depending on the results of the FACBC scan, your doctor may recommend biopsy of suspicious areas or 
other therapies. 
Follow-Up 
All patients will also be followed for a minimum of three (3) years with blood draws for PSA levels every six (6) 
months. We may follow your medical progress for up to five years total. 
Risks 
You may have side effects while on the study. Everyone taking part in the study will be watched carefully for any 
side effects. However, researchers don’t know all the side effects that may happen. Side effects may be mild or 
very serious. Your health care team may give you medicines to help lessen side effects. Many side effects go away 
soon after you stop radiation). In some cases, side effects can be serious, long lasting, or may never go away. In 
addition, some of the side effects may be life threatening and, in rare instances, may cause death.   
The procedures described in this study may cause all, some, or none of the side effects listed here. These are 
common procedures that are considered relatively safe. Previously unknown side effects can also occur. If new 
side effects are reported, you will be told. It is also important that you give us accurate and complete information 
about your past medical history.  
You may also find it uncomfortable to lie motionless during the approximately 30 minutes necessary to complete 
the scan.  If you believe you cannot lie still for 30 minutes, you should not participate in this study. 
Although the risk is small, it is possible to develop an allergic reaction to the FACBC.  This can result in hives, rash, 
itching and difficulty breathing which may require emergency medical treatment.  There have been no previous 
instances of allergic reaction. 
FACBC: In previous studies with 100 patients, there were no problems reported. However it is important to report 
any unusual side effects that you are having such as itching, skin rashes, fever, chills, nausea, dizziness, and 
vomiting. Please also see the risks of radiation exposure below. 
Radiation Exposure:  
This research study involves exposure to radiation from PET/CT scans, similar to those routinely used for medical 
purposes. This radiation dose is not necessary for your medical care and will occur only as a result of your participation 
in this study. The radiation dose that you will receive is estimated to be equal to or less than the annual radiation 


Study No.: «ID» 
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Document Approved On: «ApproveDate» 
Page 5 of 12 
Version Date: 03/07/2018 
IRB Form 12152017 
exposure limit allowed for persons who are occupationally exposed to radiation (for example, x-ray technologist, and 
radiologist).  The principal risk associated with a radiation dose is the possibility of developing a radiation-induced 
cancer later in life. The risk for radiation-induced cancer from this study is minimal.  The risk from radiation exposure of 
this magnitude is considered to be comparable to other everyday risks. There are currently no studies that show an 
increase in the risk of genetic mutation in the next generation of offspring. 
Risks and side effects related to the radiation therapy include those which are: 
Likely 
•
Tanning, redness, or darkening of skin in treatment area
•
Rash, itching or peeling of skin
•
Temporary hair loss in the treatment area
•
Temporary fatigue
•
Abdominal cramps
•
Frequent bowel movements, sometime with urgency, or diarrhea
•
Rectal cramps and irritation with pain on defecation
•
Mild rectal bleeding that does not require treatment
•
Bladder irritation with a stinging sensation
•
Frequency or urgency of urination
•
Small amounts of blood in the urine
Less Likely 
•
Urinary obstruction requiring the placement of a temporary urinary catheter and/or dilatation because of
stricture (narrowing) 
•
Less ability to control urine (increased incontinence)
•
Inability to achieve an erection (inability of the penis to become hard)
•
Rectal bleeding that requires medication or laser treatment to stop
Rare but serious 
•
Injury to the bladder, urethra, bowel, or other tissues in the pelvis or abdomen requiring additional procedure or
surgery, such as a colostomy (bag for stool) 
•
Intestinal obstruction requiring surgery
Reproductive risks 
You should not father a baby nor donate sperm while on this study or during the first 3 months after cessation of 
therapy because the drugs and radiation in this study can affect an unborn baby. Check with your study doctor about 
what kind of birth control methods to use and how long to use them.  
Intravenous Catheter: One tube will be placed in your vein (arm or hand.) It is called an intravenous catheter or IV. 
It is placed under sterile conditions by piercing the skin and underlying vein with a needle, over which is threaded 
the IV catheter and then the needle is withdrawn. When the catheter is placed or removed, the site of insertion 
may become sore or bruised. Rarely, bleeding or infection can occur at this site; however, this is highly unlikely. A 
small gauze pad or bandage is placed over the site after the IV catheter is removed. This is similar to what 
happens when one donates blood. 
Vein Puncture 
. Care will be taken to minimize these risks. 
New Findings 


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IRB Form 12152017 
We may learn new things during the study that you may need to know. We can also learn about things that might 
make you want to stop participating in the study. If so, you will be notified about any new information. 
Benefits 
Taking part in this research study may not benefit you personally. The outcome for patients randomized to Group 2 may 
or may not be as good, or may be better, than patients in Group 1 receiving standard of care.  We do know that the 
information from this study will help researchers learn more about how best to treat men who have a rising PSA after 
surgery to remove their prostate. This information could help future cancer patients 
Compensation 
If you were enrolled in Arm 2 of the study, we will compensate you $50.00 for travel expenses to Emory for the PET 
scan. 
Alternatives 
Your other choices may include: 
•
Getting treatment or care for your cancer without being in a study; this could include the following options,
either alone or in combination with each other: 
o
External beam radiation therapy (typically, to the prostate bed)
o
External beam radiotherapy plus hormone therapy
o
Hormone therapy
•
Taking part in another study
•
Getting no treatment (With this choice, your tumor could continue to grow and your disease could spread )
Talk to your doctor about your choices before you decide if you will take part in this study. 
Confidentiality 
Emory, Saint Joseph’s Hospital, or Grady Health System will keep any research records that it creates private to the 
extent that this is required to do so by law.  Whenever possible, a study number, rather than your name, will be used on 
study records.  Your name and other identifying information will not appear when we present or publish the study 
results. 
Certificate of Confidentiality 
There is a Certificate of Confidentiality from the National Institutes of Health for this Study.  The Certificate of 
Confidentiality helps us to keep others from learning that you participated in this study.  Emory will rely on the 
Certificate of Confidentiality to refuse to give out study information that identifies you.  For example, if Emory received a 
subpoena for study records, it would not give out information that identifies you. 
The Certificate of Confidentiality does not stop you or someone else, like a member of your family, from giving out 
information about your participation in this study.  For example, if you let your insurance company know that you are in 
this study, and you agree to give the insurance company research information, then the investigator cannot use the 
Certificate to withhold this information. This means you and your family also need to protect your own privacy. 
The Certificate does not stop Emory from making the following disclosures about you: 
•
Giving state public health officials information about certain infectious diseases,
•
Giving law officials information about abuse of a child, elderly person or disabled person.
•
Giving out information to prevent harm to you or others.


Study No.: «ID» 
Emory University IRB 
IRB use only 
Document Approved On: «ApproveDate» 
Page 7 of 12 
Version Date: 03/07/2018 
IRB Form 12152017 
•
Giving the study sponsor or funders information about the study, including information for an audit or
evaluation.
Medical Record 
If you are or have been a patient at an Emory, Saint Joseph’s Hospital, or Grady Health System, then you will have an 
Emory, Saint Joseph’s Hospital,  or Grady health System medical record. If you are not and have never been a patient at 
an Emory, Saint Joseph’s Hospital, or Grady Health System facility then you do not have one. An Emory, Saint Joseph’s 
Hospital, or Grady Health System medical record will be made for you if you have any services or procedures done by an 
Emory, Saint Joseph’s Hospital, or Grady Health System provider or facility for this study. 
Copies of the informed consent form and HIPAA authorization form that you sign will be placed in your Emory, Saint 
Joseph’s Hospital, or Grady Health System medical record. Emory, Saint Joseph’s Hospital, or Grady Health System may 
create study information that can help Emory, Saint Joseph’s Hospital, or Grady Healthcare take care of you. For 
example, the results from study tests and procedures. These useful study results will be placed in your Emory, Saint 
Joseph’s Hospital, or Grady Health System medical record. Anyone who has access to your medical record will be able to 
have access to all study information placed there The confidentiality of the study information in your medical record will 
be protected by laws such as HIPAA Privacy Rule. On the other hand, some state and federal laws and rules may not 
protect the research information from disclosure. 
Emory, Saint Joseph’s Hospital, or Grady Health System do not control results from tests and procedures performed 
and/or analyzed at other places, so these result would not be placed in your Emory, Saint Joseph’s Hospital ,or Grady 
Health System medical record. They will not necessarily be available to Emory, Saint Joseph’s Hospital, or Grady Health 
System to help take care of you.  Emory, Saint Joseph’s Hospital, or Grady Health System  also do  not have control over 
any other medical records that you may have with other healthcare providers and will not send any test or procedure 
results from the study to these providers. It is up to you to let these healthcare providers know that you are participating 
in a clinical trial.   
Some tests and procedures that may be performed during this study by Emory, Saint Joseph’s Hospital, or Grady 
Healthcare or other facilities or persons may not be looked at or read for any healthcare treatment or diagnostic 
purposes. These tests and procedures will only be looked at for research purposes and the results will not be reviewed 
to make decisions about your personal health or treatment except as explained earlier. The specific types of tests or 
procedures, if any, that fall within this category are listed below: 
FACBC PET scan 
A Data Safety Monitoring Board will be regularly meeting to monitor safety and other data related to this study.  The 
Board members may receive confidential patient information, but they will not receive your name or other information 
that would allow them to identify you by name. 
Authorization to Use and Disclose Protected Health Information 
The privacy of your health information is important to us.  We call your health information that identifies you, your 
“protected health information” or “PHI.”  To protect your PHI, we will follow federal and state privacy laws, including the 
Health Insurance Portability and Accountability Act and regulations (HIPAA).  We refer to all of these laws as the “Privacy 
Rules.”  Here we let you know how we will use and disclose your PHI for this study. 
PHI that will be Used/Disclosed:   
The PHI that we will use and/or disclose (share) for the research study includes 
•
Entire medical record.


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IRB Form 12152017 
•
Results of exams, procedures and tests you have before and during the study including pathology results,
laboratory results, and radiology results.
•
FACBC PET scan results.
Purposes for which your PHI will be Used/Disclosed: 
We will use and disclose your PHI for the conduct and oversight of the research study.  We will use and share your PHI to 
provide you with study related treatment and for payment for such treatment.  We will also use and share your PHI to 
conduct normal business operations.  We may share your PHI with other people and places that help us conduct or carry 
out the study, such as laboratories, data management centers, data monitors, contract research organizations, 
Institutional Review Boards (IRBs) and other study sites. If you leave the study, we may use your PHI to determine your 
health, vital status or contact information. We will use and disclose your PHI for the administration and payment of any 
costs relating to subject injury from the study.   
Use and Disclosure of Your Information that is Required by Law:   
We will use and disclose your PHI when we are required to do so by law. This includes laws that require use to report 
child abuse or abuse of elder or disabled adults. We will also comply with legal requests or orders that require us to 
disclose your PHI. These include subpoenas or court orders.   
Authorization to Use PHI is Required to Participate: 
By signing this form, you give us permission to use and share your PHI as described in this document. You do not have to 
sign this form to authorize the use and disclosure of your PHI.  If you do not authorize the use and disclosure of your PHI 
for the study, then you may not participate in the research study or receive research-related treatment.  You may still 
receive non-research related treatment.   
People that will Use and/or Disclose Your PHI: 
The following people and groups will use and disclose your PHI in connection with the research study: 
•
The Principal Investigator and the research staff will use and disclose your PHI to conduct the study and give you
study related treatment.
•
Emory and Saint Joseph’s Hospital may use and disclose your PHI to get payment for study related treatment
and to run normal business operations.
•
The Principal Investigator and research staff will share your PHI with other people and groups to help conduct
the study or to provide oversight for the study.
•
The National Institute of Health is the Sponsor of the study.  The Sponsor may use and disclose your PHI to make
sure the research is done correctly and to collect and analyze the results of the research.  The Sponsor may
disclose your PHI to other people and groups like study monitors to help conduct the study or to provide
oversight for the study.
•
The research team and the Sponsor may use and disclose your PHI, including disclosure to insurance carriers to
administer payment for subject injury.
•
The following people and groups will use your PHI to make sure the research is done correctly and safely:
o
Emory offices that are part of the Human Research Participant Protection Program and those that
involved in study administration and billing.  These include the Emory IRB, Western IRB, and other IRBs
or privacy boards involved in this study; the Emory Research and Healthcare Compliance Offices; and the
Emory Office for Clinical Research.
o
The Institutional Review Board at Saint Joseph’s Hospital.
o
Grady Health System Research Oversight Committee.
o
Grady Health Systems or Saint Joseph’s Hospital offices involved in the study administration and billing.


Study No.: «ID» 
Emory University IRB 
IRB use only 
Document Approved On: «ApproveDate» 
 
 
Page 9 of 12 
 
Version Date: 03/07/2018 
IRB Form 12152017 
o Government agencies that regulate the research including:  Office for Human Research Protections; 
Food and Drug Administration. 
o Public health agencies. 
o Research monitors and reviewer. 
o Accreditation agencies. 
 
Expiration of Your Authorization 
This authorization will not expire because it is a research study. 
 
Revoking Your Authorization 
If you sign this form, at any time later you may revoke (take back) your permission to use your information.  If you want 
to do this, you must write to: 
 
Dr. Ashesh B. Jani 
Department of Radiation Oncology 
 
Atlanta, GA 30322 
Tel: 
  
Email: 
 
 
At that point, the researchers would not collect any more of your PHI.  But they may use or disclose the information you 
already gave them so they can follow the law, protect your safety, or make sure that the study was done properly and 
the data is correct.  If you revoke your authorization you will not be able to stay in this study.  
 
Other Items You Should Know 
Not all people and entities are covered by the Privacy Rules.  HIPAA only applies to health care providers, health care 
payers or health care clearinghouses.  If we disclose your information to people who are not covered by the Privacy 
Rules, including HIPAA, then your information won’t be protected by the Privacy Rules.  People who do not have to 
follow the Privacy rules can use or disclose your information with others without your permission if they are allowed to 
do so by the laws that cover them.   
 
To maintain the integrity of this research study, you generally will not have access to your PHI related to this research 
until the study is complete.  When the study ends, and at your request, you generally will have access to your PHI that 
we maintain in a designated record set.  A designated record set is data that includes medical information or billing 
records that your health care providers use to make decisions about you. If it is necessary for your health care, your 
health information will be provided to your doctor.  
 
We may remove identifying information from your PHI.  Once we do this, the remaining information will not be subject 
to the Privacy Rules.  Information without identifiers may be used or disclosed with other people or organizations and/or 
for other purposes besides this study.   
 
In case of Injury 
If you are injured by or become ill from being in the study, Emory, Saint Joseph’s Hospital, or Grady Health System would 
help you get medical treatment. If you believe you have been injured by this research, you should contact Dr. Schuster. 
Phone: 
 or Dr. Ashesh B. Jani, 
if you are being treated at the Emory Clinic. You should also 
let any health care provider who treats you know that you are in a research study. At Saint Joseph’s Hospital contact Dr. 
Bruce Hershatter at 
 At Grady Healthcare contact Dr. Joseph Shelton at 
 


Study No.: «ID» 
Emory University IRB 
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Document Approved On: «ApproveDate» 
 
 
Page 10 of 12 
 
Version Date: 03/07/2018 
IRB Form 12152017 
If you get ill or injured as the direct result of being in this study, then, depending on what insurance you may have, the 
sponsor may pay for some or all of the costs for your medical treatment of the illness or injury if  it: 
(a) is not a medical condition that you had before you started the study; 
(b) is not the result of the natural progress of your disease or condition; 
(c) is not caused by your failure to follow the study plan; and   
(d) is not proved to be directly caused by the negligence of an Emory employee.  “Negligence” is the failure to 
follow a standard duty of care.  
If your case meets all four of these requirements and you are uninsured or have Medicare or Medicaid, then the sponsor 
will pay all of the costs of your medical treatment for the illness or injury. 
If your case meets all four of these requirements and you have private insurance, Emory or Grady Health System will 
look at the claims for these costs to see if they can be sent to your insurer for payment.  Your insurer may be told that 
you are in a research study and given information about your treatment.   
You will have to pay for any costs that the sponsor or your insurer does not pay. The sponsor will pay for any of the costs 
that are not paid by your insurance provider. The sponsor will not pay for costs like co-payments that your insurer says 
you have to pay.  
Emory, Saint Joseph’s Hospital, and Grady Health System have not set aside any money to pay you or to pay for your 
treatment if you get ill or injured from being in the study.  The only exception to this policy is if it is proved that your 
injury or illness is directly caused by the negligence of Emory, Saint Joseph’s Hospital, Grady Health System, or sponsor 
employee. 
Costs 
You will not be charged for the FACBC PET scans, urinalysis, or blood work that is done before the FACBC and one week 
after. These costs will be paid for by the Sponsor. 
 
You will have to pay for the items or services for which the study sponsor does not pay. The sponsor will not pay for your 
regular medical care including any other care you receive related to your prostate problem, including the bone scan, CT 
or MRI scans, biopsies, radiation therapy, hormonal or other therapy.  
If you have insurance, Emory or Grady Health System will submit claims to your insurance for items and services that the 
sponsor does not cover.  Emory or Grady Health System will send in only those claims for items and services that it 
reasonably believes your insurance will pay and that the sponsor has not paid.  
 
The actual amount that you have to pay depends on whether or not you have health insurance and whether or not that 
insurance will pay for any research study costs. Generally, insurance companies will not pay for items and services that 
are required just for a research study. Some insurance companies will not pay for regular medical treatment or 
treatment for complications if you are in a study.  How much you will have to pay for any co-payments, deductibles or 
co-insurance depends on your plan.  Emory, Saint Joseph’s Hospital, Grady Health System, and the sponsor will not pay 
for these costs.  
 
It is a good idea to contact your insurance provider and tell them you want to be in this research study.  Ask them what 
they will pay for and what they will not pay for.  You can also ask the study team for help in figuring out what you will 
have to pay.  
 


Study No.: «ID» 
Emory University IRB 
IRB use only 
Document Approved On: «ApproveDate» 
 
 
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Version Date: 03/07/2018 
IRB Form 12152017 
If you do not have insurance, Emory, Saint Joseph’s Hospital, or Grady Health System will review your case as part of its 
program for low-income patient care.  The standard policies of that program will apply.  The program will figure out if 
you have to pay any costs for taking part in the study and what those costs will be. 
 
Disclosure of Financial Interest 
Emory University and Dr. Goodman have a financial interest in the radiopharmaceutical FACBC being studied in this 
study because Emory has licensed the radiopharmaceutical FACBC to Nihon Medi-Physics Co.  Emory University and Dr. 
Goodman receive research funding and are entitled to sales royalty from Nihon Medi-Physics, which is developing 
products related to the research.  The terms of this arrangement have been reviewed and approved by Emory University 
in accordance with its conflict of interest policies. 
 
Voluntary Participation and Withdrawal 
Your participation is completely voluntary and you have the right to refuse to be in this study.  You can stop at any time 
after giving your consent. This decision will not affect in any way your current or future medical care or any other 
benefits to which you are otherwise entitled.  
 
The study doctors have the right to end your participation in this study without your consent for any of the following 
reasons:   
• It would be dangerous for you to continue;  
• you were to object to any future changes that may be made in the study plan; 
• do not follow study procedures as directed by the study doctors;  
• the sponsor decides to end the study. 
 
Contact Persons:  
If you have any questions about this study call the study coordinator. Call Dr. David Schuster or Dr. Ashesh Jani, if you 
have been harmed from being in this study. Call Dr. David Schuster if you have questions concerning the risk of radiation 
their telephone numbers are: 
Dr. Ashesh B. Jani:  
 
Dr. David Schuster:   
 
Bridget Fielder, RN (Study Coordinator):  
 
 
Contact the Emory Institutional Review Board at
 or 
 
• 
If you have questions about your rights as a research participant. 
• 
If you have questions, concerns or complaints about the research.  You may also let the IRB know about your 
experience as a research participant through our Research Participant Survey at 
http://www.surveymonkey.com/s/6ZDMW75 
 
If you are a patient receiving care from the Grady Health System and you have a question about your rights, you may contact 
the Office of Research Administration at 
 
 
 
 
 
 
 
 
 


Study No.: «ID» 
Emory University IRB 
IRB use only 
Document Approved On: «ApproveDate» 
 
 
Page 12 of 12 
 
Version Date: 03/07/2018 
IRB Form 12152017 
Consent and Authorization 
 
TO BE FILLED OUT BY SUBJECT ONLY 
Please print your name, sign, and date below if you agree to be in the main study. By signing this consent and 
authorization form, you will not give up any of your legal rights. We will give you a copy of the signed form to 
keep. 
 
 
 
Name of Subject  
 
 
 
 
 
 
 
_________________ 
 
___ 
____:____ am / pm 
Signature of Subject (18 or older and able to consent) 
Date  
Time (please circle) 
 
 
TO BE FILLED OUT BY STUDY TEAM ONLY 
 
_________________________________________________________ 
Name of Person Conducting Informed Consent Discussion 
 
 
 
 
 
 
 
_________________ 
 
___ 
____:____ am / pm 
Signature of Person Conducting Informed 
Date  
Time (please circle) 
Consent Discussion 
 
 
 
Study Coordinator (initial if applicable): 
 
_______ 
I attest that I participated in the informed consent discussion with the subject 
_______ 
I attest that I was present when the subject gave informed consent 
 
 
 
 
 
 
_______  
 
 
 
Signature of Study Coordinator 
 
Date