Conditions: Metastatic Prostate Carcinoma Stage IVB Prostate Cancer AJCC v8
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 2
Healthy volunteers: no

Brief summary:
This phase IV trial studies how well an investigational scan (18F-fluciclovine PET-CT) works for the measurement of therapeutic response in patients with prostate cancer that has spread to other places in the body (metastatic). 18F-fluciclovine is a radioactive substance that is used in this study with PET-CT imaging scans that may help doctors learn about response to standard therapy in patients with prostate cancer.

Detailed description:
PRIMARY OBJECTIVE:

I. Evaluate metabolic response by fluciclovine F18 (18F-fluciclovine) PET qualitatively and semi-quantitatively with standardized uptake values (SUV) following androgen deprivation therapy (ADT) plus abiraterone at 22-28 weeks (+/- 4 weeks), and correlate the findings with size changes as defined by conventional imaging and prostate-specific antigen (PSA) response.

SECONDARY OBJECTIVES:

I. To correlate pelvic 18F-fluciclovine PET imaging findings with pathologic findings at radical prostatectomy and pelvic lymph node dissection to determine 18F-fluciclovine PET imaging sensitivity and specificity for pelvic lymph node cancer involvement.

II. To evaluate 18F-fluciclovine PET imaging response and its correlation with progression free survival (defined by Prostate Cancer Working Group 2 \[PCWG2\] criteria).

III. To determine if sites of progressive disease develop at the initial/prior site (diagnostic site) of metastases or in newly developed sites at the time of metastatic progression.

IV. To evaluate metabolic response by 18F-fluciclovine PET semi-quantitatively with target to blood pool ratio (TBR) following ADT plus abiraterone at 22-28 weeks (+/- 4 weeks), and correlate the findings with size changes as defined by conventional imaging and PSA response.

OUTLINE:

Within 4 weeks before starting standard systemic therapy (SST), patients receive fluciclovine F18 intravenously (IV) then undergo a PET-CT scan over 30 minutes. Within 22-28 weeks after starting SST, patients receive fluciclovine F18 IV and undergo a second PET-CT scan over 30 minutes.

Arms:
arm 1: Within 4 weeks before starting SST, patients receive fluciclovine F18 IV then undergo a PET-CT scan over 30 minutes. Within 22-28 weeks after starting SST, patients receive fluciclovine F18 IV and undergo a second PET-CT scan over 30 minutes.

Interventions: intervention 1: Computed Tomography intervention 2: Fluciclovine F18 intervention 3: Positron Emission Tomography
Intervention descriptions: intervention 1: Undergo PET-CT scan intervention 2: Given IV intervention 3: Undergo PET-CT scan

Protocol document:
ICF_007.pdf: 
Protocol 2019-0030 
January 26, 2021 
Page 1 of 8 
 
Informed Consent 
 
 
INFORMED CONSENT/AUTHORIZATION FOR PARTICIPATION IN 
RESEARCH 
 
18F-fluciclovine PET-CT as an indicator of therapeutic response in 
metastatic prostate carcinoma (M1PCa) 
2019-0030  
 
Study Chair: 
Gregory Ravizzini 
 
_________________________ 
_____________________ 
Participant’s Name 
 
 
Medical Record Number  
 
This is an informed consent and authorization form for a research study. It includes 
a summary about the study. A more detailed description of procedures and risks is 
provided after the summary.  
 
STUDY SUMMARY 
 
 
The goal of this clinical research study is to learn if a radioactive imaging agent called 
18F-fluciclovine used during a PET-CT scan can further help measure changes in 
tumor size. The results of these scans will be compared to standard of care imaging 
scans. 
This is an investigational study. 18F-fluciclovine is an FDA-approved and 
commercially available radioactive imaging agent for PET/CT scans in adult males 
with suspected prostate cancer. The PET-CT scans are performed using FDA 
approved and commercially available methods. The use of 18F-fluciclovine to measure 
changes in tumor size in this study is investigational. 
 
Future patients may benefit from what is learned from your participation in this study. 
There are no direct benefits for you in this study. 
 
Your participation is completely voluntary. Before choosing to take part in this study, 
you should discuss with the study team any concerns you may have, including side 
effects, potential expenses, and time commitment. If you take part in this study, you 
may experience pain or redness at the injection site or a change in taste.  
 
You can read a list of potential side effects below in the Possible Risks section of this 
consent. 


Protocol 2019-0030 
January 26, 2021 
Page 2 of 8 
 
Your active participation in this study will be over after the post-treatment 18F-
fluciclovine PET-CT scan. 
 
The 18F-fluciclovine PET-CT scans will be provided at no cost to you while taking part 
in this study. 
 
You may choose not to take part in this study.  
 
1.  STUDY DETAILS 
 
If you agree to take part in this study, you will have two (2) 18F-fluciclovine PET-CT 
scans in addition to some of the standard of care  tests, procedures, bone scans, CT 
scans, and PET-CT scans without 18F-fluciclovine.  
 
For the 18F-fluciclovine PET-CT scans, you will receive an injection of the imaging 
agent 18F-fluciclovine into a vein through a standard catheter while you lie in the 
scanner. The 18F-fluciclovine PET-CT scan will last about 30 minutes. 
 
Within 30 days before and then 22-28 weeks after starting systemic therapy, you 
may have some of the standard of care imaging scans listed above and a research 
18F-fluciclovine PET-CT scan.  
 
Up to 45 participants will be enrolled in this study. All will take part at MD Anderson. 
 
2.  POSSIBLE RISKS 
 
While on this study, you are at risk for side effects. You should discuss these with the 
study doctor. The known side effects are listed in this form, but they will vary from 
person to person. 
 
18F-fluciclovine may cause a feeling of warmth or pain at the injection site. It may 
cause headache and dizziness. It may cause hypersensitivity reactions which may 
cause breathing and/or skin problems (rash, redness, blisters, itching, and/or local 
swellings) and may appear either immediately or up to a few days after the injection.  
It may cause anaphylactic shock (a severe allergic reaction that can cause breathing 
difficulty and/or a drop in blood pressure).  It may cause changes in the way you move 
or changes in your senses. 
 
A PET-CT scan may cause you to feel “closed in” while lying in the scanner. 
However, the scanner is open at both ends and an intercom allows you to talk with 
doctors and staff.  If you feel ill or anxious during scanning, doctors and/or technicians 
will give comfort or the scanning will be stopped. 
 
The PET-CT scan exposes your body to radiation. The radioactive solution does not 
remain in your system for a long period of time. However, you should wait 2 hours 


Protocol 2019-0030 
January 26, 2021 
Page 3 of 8 
before holding an infant or getting close to a pregnant woman to avoid exposing them 
to radiation.  You should drink fluids after the scan to help remove the solution from 
your system. 
 
This study may involve unpredictable risks to participants. 
 
 
3. COSTS AND COMPENSATION  
 
If you suffer injury as a direct result of taking part in this study, MD Anderson health 
providers will provide medical care. However, this medical care will be billed to your 
insurance provider or you in the ordinary manner. You will not be reimbursed for 
expenses or compensated financially by MD Anderson or Blue Earth Diagnostics for 
this injury. You may also contact the Chair of MD Anderson’s IRB at 713-792-6477 
with questions about study-related injuries. By signing this consent form, you are 
not giving up any of your legal rights. 
 
Certain tests, procedures, and/or drugs that you may receive as part of this study 
may be without cost to you because they are for research purposes only. However, 
your insurance provider and/or you may be financially responsible for the cost of 
care and treatment of any complications resulting from the research tests, 
procedures, and/or drugs. Standard medical care that you receive under this 
research study will be billed to your insurance provider and/or you in the ordinary 
manner. Before taking part in this study, you may ask about which parts of the 
research-related care may be provided without charge, which costs your insurance 
provider may pay for, and which costs may be your responsibility. You may ask that 
a financial counselor be made available to you to talk about the costs of this study. 
 
There are no plans to compensate you for any patents or discoveries that may 
result from your participation in this research.  
 
You will receive no compensation for taking part in this study.  
 
Additional Information  
 
4. 
You may ask the study chair (Dr. Gregory Ravizzini, at 713-745-5721) any 
questions you have about this study. You may also contact the Chair of MD 
Anderson's Institutional Review Board (IRB - a committee that reviews research 
studies) at 713-792-6477 with any questions that have to do with this study or your 
rights as a study participant. 
 
5. 
You may choose not to take part in this study without any penalty or loss of 
benefits to which you are otherwise entitled. You may also withdraw from 
participation in this study at any time without any penalty or loss of benefits. If you 
decide you want to stop taking part in the study, it is recommended for your safety 
that you first talk to your doctor. If you withdraw from this study, you can still 


Protocol 2019-0030 
January 26, 2021 
Page 4 of 8 
choose to be treated at MD Anderson. 
 
6. 
This study or your participation in it may be changed or stopped without your 
consent at any time by the study chair, Blue Earth Diagnostics, the U.S. Food and 
Drug Administration (FDA), the Office for Human Research Protections (OHRP), 
or the IRB of MD Anderson. 
 
7. 
You will be informed of any new findings or information that might affect your 
willingness to continue taking part in the study. Results of 18F-fluciclovine PET/CT 
scans and all of your standard tests performed as part of this research will be 
available to you and recorded on the electronic medical records. You may be 
asked to sign another informed consent and authorization form stating your 
continued willingness to participate in this study. 
 
8. 
MD Anderson may benefit from your participation and/or what is learned in this 
study. 
 
9.     This study is sponsored and/or supported by: Blue Earth Diagnostics. 
 
10.  In a medical emergency, you may be cared for by someone who has a financial 
interest with the study sponsor(s)/supporter. If you have any questions about this, 
you may call the IRB at 713-792-6477. 
 
Future Research 
 
Your personal information is being collected as part of this study. This information, 
or data, may be used by researchers at MD Anderson or shared with other 
researchers and/or institutions for use in future research.  
 
Before being shared for future research, every effort will be made to remove your 
identifying information from any data. If all identifying information is removed, you 
will not be asked for additional permission before future research is performed.  
 
In some cases, all of your identifying information may not be removed before your 
data are used for future research. If this research is performed at MD Anderson, the 
researchers must get approval from the Institutional Review Board (IRB) of MD 
Anderson before your data can be used. At that time, the IRB will decide whether or 
not further permission from you is required. The IRB is a committee of doctors, 
researchers, and community members that is responsible for protecting study 
participants and making sure all research is safe and ethical.  
 
If this research is not performed at MD Anderson, MD Anderson will not have 
oversight of any data. 
 
Conflict of Interest 
 


Protocol 2019-0030 
January 26, 2021 
Page 5 of 8 
Dr. Brian Chapin (Collaborator) has received compensation from Blue Earth 
Diagnostics as a Consultant.  The financial interests are within the limits of the 
conflict of interest policy. 
 
Authorization for Use and Disclosure of Protected Health Information (PHI): 
 
A.  During the course of this study, MD Anderson will be collecting and using your 
PHI, including identifying information, information from your medical record, and 
study results. For legal, ethical, research, and safety-related reasons, your doctor 
and the research team may share your PHI with: 
• 
Federal agencies that require reporting of clinical study data (such as the 
FDA, National Cancer Institute [NCI], and OHRP) 
• 
The IRB and officials of MD Anderson 
• 
Blue Earth Diagnostics, who is a sponsor or supporter of this study, and/or 
any future sponsors/supporters of the study 
• 
Study monitors and auditors who verify the accuracy of the information 
• 
Individuals who put all the study information together in report form 
 
Study sponsors and/or supporters receive limited amounts of PHI. They may also 
view additional PHI in study records during the monitoring process. MD 
Anderson’s contracts require sponsors/supporters to protect this information and 
limit how they may use it.  
 
B. 
Signing this consent and authorization form is optional but you cannot take part in 
this study or receive study-related treatment if you do not agree and sign. 
 
C. 
MD Anderson will keep your PHI confidential when possible (according to state 
and federal law). However, in some situations, the FDA could be required to 
reveal the names of participants. 
 
Once disclosed outside of MD Anderson, federal privacy laws may no longer 
protect your PHI. 
 
D.  The permission to use your PHI will continue indefinitely unless you withdraw your 
authorization in writing. Instructions on how to do this can be found in the MD 
Anderson Notice of Privacy Practices (NPP) or you may contact the Chief Privacy 
Officer at 713-745-6636. If you withdraw your authorization, you will be removed 
from the study and the data collected about you up to that point can be used and 
included in data analysis. However, no further information about you will be 
collected. 
 
 E.  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 can 
search this Web site at any time. 
 


Protocol 2019-0030 
January 26, 2021 
Page 6 of 8 
 
 


Protocol 2019-0030 
January 26, 2021 
Page 7 of 8 
CONSENT/AUTHORIZATION 
I understand the information in this consent form.  I have had a chance to read the 
consent form for this study, or have had it read to me. I have had a chance to think 
about it, ask questions, and talk about it with others as needed. I give the study chair 
permission to enroll me on this study.  By signing this consent form, I am not giving up 
any of my legal rights. I will be given a signed copy of this consent document. 
 
________________________________________ 
_______ 
SIGNATURE OF PARTICIPANT 
DATE 
 
_________________________________         
PRINTED NAME OF PARTICIPANT                 
 
LEGALLY AUTHORIZED REPRESENTATIVE (LAR) 
The following signature line should only be filled out when the participant does not have 
the capacity to legally consent to take part in the study and/or sign this document on his 
or her own behalf. 
_____________________________________________________ 
_________ 
SIGNATURE OF LAR 
DATE 
 
 
 
PRINTED NAME and RELATIONSHIP TO PARTICIPANT 
 
WITNESS TO CONSENT 
I was present during the explanation of the research to be performed under Protocol 
2019-0030. 
_____________________________________________________  
_________ 
SIGNATURE OF WITNESS TO THE VERBAL CONSENT  
  
DATE  
PRESENTATION (OTHER THAN PHYSICIAN OR STUDY CHAIR) 
A witness signature is only required for vulnerable adult participants. If witnessing the assent of a 
pediatric participant, leave this line blank and sign on the witness to assent page instead. 
 
 
PRINTED NAME OF WITNESS TO THE VERBAL CONSENT 
 
PERSON OBTAINING CONSENT 
I have discussed this research study with the participant and/or his or her authorized 
representative, using language that is understandable and appropriate.  I believe that I 
have fully informed this participant of the nature of this study and its possible benefits 
and risks and that the participant understood this explanation. 
 
______________________________________________ 
  
_________ 
PERSON OBTAINING CONSENT  
 
 
 
 
 
DATE 
 
______________________________________________ 
PRINTED NAME OF PERSON OBTAINING CONSENT 
 


Protocol 2019-0030 
January 26, 2021 
Page 8 of 8 
TRANSLATOR 
I have translated the above informed consent as written (without additions or 
subtractions) into 
and assisted the people 
(Name of Language) 
obtaining and providing consent by translating all questions and responses during the 
consent process for this participant. 
 
 
_____________________       _______________________________    
___________ 
NAME OF TRANSLATOR       SIGNATURE OF TRANSLATOR 
 DATE 
 
   Please check here if the translator was a member of the research team.  (If checked, 
a witness, other than the translator, must sign the witness line below.) 
 
____________________________________________________   
___________ 
SIGNATURE OF WITNESS TO THE VERBAL TRANSLATION  
  
DATE  
(OTHER THAN TRANSLATOR, PARENT/GUARDIAN,  
OR STUDY CHAIR) 
 
_____________________________________________________ 
PRINTED NAME OF WITNESS TO THE VERBAL TRANSLATION 
 
 

Prot_SAP_006.pdf: 
1 
Protocol Title: 18F‐Fluciclovine PET CT as an indicator of therapeutic response in metastatic 
prostate carcinoma (M1PCa). 
Study Chair (PI) 
Gregory C. Ravizzini, M.D. 
Associate Professor 
Department of Nuclear Medicine 
The University of Texas MD Anderson Cancer Center 
1515 Holcombe Blvd 
Houston, Texas 77030 
Co‐Principal Investigators:  
Diagnostic Radiologists: 
Tharakeswara K Bathala, M.D. 
Nuclear Medicine Specialist: 
Homer Macapinlac, MD 
Radiation Oncologists 
Karen Hoffman, M.D 
Medical Oncologist 
Ana Aparicio, M.D 
Surgical Oncologist (Urology) 
Brian F. Chapin, M.D. 
Physicist 
Osama Mawlawi, Ph.D. 
Statistical Analyst 
Roland L. Bassett, Jr., M.S. 
Jia Sun Ph.D  
Proprietary of MD Anderson Cancer  Center MDACC ID: 2019-0030 
NCT ID: NCT041324208 
Document Date: 7/28/2021


2 
 
Table of Contents 
 
1.0 
Protocol Overview (Schema) 
 
2.0 
Background and Rationale 
 
3.0 
Study Objectives 
 
4.0 
Eligibility Criteria 
 
5.0 
Research Design and Methods 
 
6.0 
Statistical Considerations 
 
7.0 
Adverse Events; Safety Issues 
 
8.0 
Ethical Issues (including Informed Consent) 
 
9.0 
Data Management; Administrative Issues 
 
10.0 
Budget 
 
11.0 
References 
Proprietary of MD Anderson Cancer  Center MDACC ID: 2019-0030 
NCT ID: NCT041324208 
Document Date: 7/28/2021


3 
 
18F‐Fluciclovine PET CT as an indicator of therapeutic response in metastatic prostate carcinoma 
(M1PCa). 
 
1.0 
PROTOCOL OVERVIEW (SCHEMA) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligible metastatic prostate cancer patients 
>/= M1a (castration naïve) 
 
PSA Testing, Bone scan, CT abdomen, Pelvic MRI 
 
Baseline 18F FluciclovinePETCT before initiation of 
SST 
 
22‐28 weeks of SST 
 
PSA Testing, Bone scan, CT abdomen, Pelvic MRI 
 
Repeat 18F FluciclovinePETCT 
Proprietary of MD Anderson Cancer  Center MDACC ID: 2019-0030 
NCT ID: NCT041324208 
Document Date: 7/28/2021


4 
 
2.0 
Background and Rationale 
In screened populations, the incidence of metastatic prostate cancer (M1 PC) at diagnosis is approximately 
1.5%.1  In  the  general  population,  the  incidence  of  M1  PC  at  diagnosis  is  approximately  5%.2  Thus,  men 
presenting with M1 PC at diagnosis represent close to one third of the 30,000 men dying from PC each year 
in the US. The treatment paradigm for M1 and clinically node positive (cN1) PC is centered on use of systemic 
therapies,  commencing  with  androgen  deprivation  therapy  (ADT)  followed  by  secondary  hormonal 
treatments  and  then  chemotherapy  upon  the  development  of  castrate  resistance,  while  definitive  local 
therapy has traditionally been reserved for treatment of localized PC.3 However, a growing body of evidence 
suggests that definitive treatment of the primary tumor may improve the outcome of men with advanced 
disease. First, two recent prospective randomized trials have shown a survival benefit for men with locally 
advanced disease that received radiation therapy in addition to ADT compared to those receiving ADT alone.4,5 
Second, retrospective studies suggest overall survival (OS) and cancer specific survival (CSS) are better in 
patients with pathologically proven lymph node positive disease that went on to receive treatment (radiation 
or prostatectomy) of their primary tumor.6‐8 Third, it has been estimated that 24‐44% of men treated with 
non‐curative  intent  will  develop  symptomatic  local  progression  requiring  intervention.9,10  Symptomatic 
progression  of  local  disease  is  a  source  of  intense  suffering  as  well  as  health  care  resource  spending, 
consumed in hospital admissions and unsatisfactory palliative procedures, and is likely to accelerate death 
from PC.9 While salvage cystoprostatectomies and pelvic exenterations can offer palliation of symptoms, they 
carry a high rate of complications and can only be offered to a subset of men in this situation.11,12 
 
From a biological perspective, recent data suggest that ADT may not provide sufficient control of the primary 
tumor, which may act as a continued source for additional metastatic spread and resistant clonal selection.13‐
15  While  there  is  evidence  that  demonstrates  prostate  cancer  has  significant  heterogeneity  within  the 
multiple foci of tumors with a gland, molecular and cytogenetic data show that multiple metastases within 
the  same  patient  are  clonally  related16‐18  suggesting  that  metastatic  clones  may  arise  from  a  selective 
advantage of individual clones and that further systemic therapies may select for cells with varying malignant 
potentials. Therefore, definitive treatment of the primary tumor may also improve outcomes by removing a 
major source of spread and thereby increasing freedom from local and distant progression, delaying time to 
castrate resistance and prolonging time to fatal metastatic burden, thus resulting in prolongation of overall 
survival. 
 
In this context, it will be important to develop a potential imaging biomarker for assessing response to SST 
which  can  potentially  differentiate  responders  vs  non‐responders  early  in  the  course  of  treatment.  It  is 
possible that SST might significantly benefit only a subset of patients and imaging biomarker could allow risk 
stratification and possible incorporation of alternative therapies at a time when they would be expected to 
be most effective. 
Proprietary of MD Anderson Cancer  Center MDACC ID: 2019-0030 
NCT ID: NCT041324208 
Document Date: 7/28/2021


5 
 
Multiple positron emission tomography (PET) tracers are available to evaluate patients with prostatic cancer, 
including fluorine‐18 fluorodeoxyglucose (18F‐FDG), 11C‐choline, PSMA and 18F FLT. However, these tracers 
have a limited role in the evaluation of response to therapy. Hence, there is a need for a radiotracer that can 
be used to more accurately assess response to therapy. 18F‐fluciclovine, is a Federal Drug Administration 
(FDA)  approved  imaging  agent  that  is  used  to  identify  disease  recurrence  after  definitive  treatment  in 
response to a rising PSA. It is a radiolabeled leucine analog (1‐amino‐3‐ fluorocyclobutane‐1‐carboxylic acid 
in  the  ‘anti’  configuration  [18F‐fluciclovine])  and  used  to  depict  amino  acid  transportation.  Amino  acid 
transporters  and  amino  acid  metabolism  are  up‐regulated  in  multiple  malignancies,  including  prostate 
cancer.  18F‐fluciclovine  has  been  shown  to  accumulate  within  prostate  cancer.19,20Although  18F‐
fluciclovine18F‐fluciclovine has been approved for the evaluation of occult disease at the time of biochemical 
recurrence, this tracer also exhibited excellent in vitro uptake in the DU145 prostate carcinoma cell line and 
within orthotopically implanted prostate tumors in nude mice.19 Moreover, since only a small fraction of 18F‐
fluciclovine is excreted through the urinary tract early after injection, its imaging characteristics are favorable 
in the prostate. 18F‐fluciclovine has been found to be successful in the assessment of primary and metastatic 
prostate cancer.21‐23 In a study of 21 patients, 18F‐fluciclovine uptake in patients with prostate cancer was 
nearly 2‐fold greater than that in patients with normal tissue.24 Schuster et al22 found a moderate correlation 
between 18F‐fluciclovine uptake and cancer aggressiveness. Although 18F‐fluciclovine has been shown to 
successfully image prostate cancer, there is currently no evidence that changes in 18F‐fluciclovine avidity 
correlate with changes in tumor burden or patient outcomes. Before 18F‐fluciclovine is used for evaluation 
of  the  tumor  response,  the  association  of  18F‐  fluciclovine  avidity  and  the  tumor  response  must  be 
established.  The  purpose  of  this  pilot  study  is  to  assess  the  ability  of  18F‐fluciclovine  positron  emission 
tomography computed tomography (PET CT) to determine the therapeutic response to SST in patients with 
metastatic prostate cancer (M1PC). 
 
3.0 
Study Objective 
Primary objective: Evaluate metabolic response by 18F‐fluciclovine PET qualitatively and semi‐quantitatively 
with standardized uptake values (SUV) following standard systemic therapy at 22‐28 weeks (+/‐ 4 weeks) and 
correlate the findings with size changes as defined by conventional imaging and PSA response. 
 
Secondary objectives: 
1. To correlate pelvic 18F‐fluciclovine PET imaging findings with pathologic findings at radical 
prostatectomy and pelvic lymph node dissection to determine 18F‐fluciclovine PET imaging 
sensitivity and specificity for pelvic lymph node cancer involvement. 
2. To evaluate 18F‐fluciclovine PET imaging response and its correlation with progression free survival 
(defined by PCWG2 criteria) 
3. To  determine  if  sites  of  progressive  disease  develop  at  the  initial/prior  site  (diagnostic  site)  of 
metastases or in newly developed sites at the time of metastatic progression.  
4. To evaluate metabolic response by 18F‐fluciclovine PET semi‐quantitatively with target to blood pool 
ratio (TBR) following SST at 22‐28 weeks (+/‐ 4 weeks), and correlate the findings with size changes 
as defined by conventional imaging and PSA response. 
 
 
4.0 
Eligibility Criteria 
For entry into this study, the following criteria must be met. Any exceptions from the 
Proprietary of MD Anderson Cancer  Center MDACC ID: 2019-0030 
NCT ID: NCT041324208 
Document Date: 7/28/2021


6 
 
protocol specific selection criteria must be approved by the principal investigator, and MD Anderson Cancer 
Center IRB, prior to enrollment. 
 
4.1 
Inclusion Criteria 
1. Male patients 
2. 18 years and older 
3. Histologically or cytologically proven prostate carcinoma 
4. Documented evidence of M1 disease by AJCC staging by Bone scan, computed tomography (CT) 
or magnetic resonance imaging (MRI) 5. Castration naive disease, no prior systemic therapy for 
prostate cancer 
Planned to receive SST 
5. ECOG PS 0 or 1 
6. Ability to understand and willingness to sign informed consent 
 
4.2 
Exclusion Criteria 
1. Known brain metastasis 
2. Small cell carcinoma of the prostate 
 
5. 0 
Research Design and Methods 
5.1 
Study Design 
A prospective pilot study will consist of eligible patients referred from genitourinary multidisciplinary 
care center at the University of Texas at MD Anderson cancer Center. All eligible patients scheduled 
to receive SST for up to 28 weeks will be enrolled, and initial 18F‐fluciclovine PET CT will be performed 
within four weeks before initiation of systemic therapy. The patient will receive SST for up to 28 
weeks, and 18F‐fluciclovine PET CT will be repeated within four weeks following SST. 18F‐fluciclovine 
PET CT will be performed as per the standard institutional protocol (Appendix C.). Blinded image 
interpretation  will  be  made  by  radiologists  and  nuclear  medicine  physician.  All  scans  will  be 
interpreted independently by two physicians. Areas of focal tracer uptake will be localized with the 
companion CT and classified as lesions of the prostate, pelvic nodes, extrapelvic nodes, visceral, and 
bone lesions. Three‐ dimensional regions of interest will be placed in areas of tracer uptake, and 
measures of 18F‐ fluciclovine avidity will be recorded; the measures include SUVmax (body weight), 
metabolic tumor volume (MTV; volume of tumor [cm3] with SUV >42% of SUVmax), SUVmean (within 
the MTV), and total lesion avidity (TLA; calculated as MTV x SUVmean). A background SUVmax will be 
documented  for  each  examination.  On  both  pretreatment  and  posttreatment  scans,  the  lesion 
SUVmax  will  be  corrected  for  the  background  as  follows:  corrected  SUVmax  =  lesion  SUVmax  ‐ 
background SUVmax. When the correct SUVmax is less than 0, 0 will be recorded. Similar corrections 
will  be  made  for  SUVmean.  When  the  corrected  SUVmax  and  the  corrected  SUVmean  are  0  on 
posttreatment scans, MTV and TLA will also be recorded as 0. The percentage of change in the 18F‐
fluciclovine SUVmax after therapy will be calculated as follows: [(pretreatment corrected SUVmax ‐ 
posttreatment corrected SUVmax)/pretreatment corrected SUVmax] x 100. Similar calculations will 
be performed for SUVmean, MTV, and TLA. 
  
Proprietary of MD Anderson Cancer  Center MDACC ID: 2019-0030 
NCT ID: NCT041324208 
Document Date: 7/28/2021


7 
 
5.2 
Reference standard 
We will calculate tumor response by using RECIST 1.1 for visceral, bone and lymph node metastasis.25 
Primary tumor within the prostate gland will be assessed based on percent reduction in tumor size, 
changes  in  restricted  diffusion  and  ADC  value  on  mp  pelvic  MRI.26‐28  In  patient  with  available 
pathological specimen following prostatectomy and pelvic LN dissection, the pathologic response 
will be used to assess tumor response as well as identification of involved lymph nodes to assess for 
specificity and sensitivity of F18 Fluciclovine to detect occult lymph node involvement. 
Patients will be dichotomized by PSA measurement is taken at six months, PSA ≤ 4 and PSA > 4.29 
 
 
Response assessment 
 
Evaluation of Target lesions 
 
Complete Response (CR) 
Disappearance of all target lesions. 
Any pathological lymph nodes (whether target or non‐target) 
must have reduction in short axis to 
<10 mm. 
Partial Response (PR) 
At least a 30% decrease in the sum of 
diameters of target lesions, taking as reference the baseline sum 
diameters. 
At least 17% increase in median ADC value within the 
tumor on DWI MR images. 
Progressive Disease (PD): 
At least a 20% increase in the sum 
of diameters of target lesions, taking as reference the smallest sum 
on study (this includes the baseline sum if that is the smallest on 
study). In addition to the relative increase of 20%, the sum must also 
demonstrate 
an absolute increase of at least 5 mm. (Note: 
the appearance of one or more new lesions is also considered 
progression). 
Stable Disease (SD): 
Neither sufficient shrinkage to qualify for 
PR nor sufficient increase to qualify for PD, taking as 
reference the smallest sum diameters while on study. 
Evaluation of non‐target lesions 
 
Complete Response (CR): 
Disappearance of all non‐target lesions 
and normalization of tumor marker level. All lymph nodes 
must be non‐pathological in size 
(<10mm short axis). 
Non‐CR/Non‐PD 
Persistence of one or more non‐target lesion ( 
s) and/or maintenance of tumor marker level 
above the normal limits. 
Progressive Disease (PD): 
Unequivocal progression (see comments below) of existing 
non‐target lesions. (Note: 
the appearance of one or more new lesions is also 
considered progression). 
 
  
5.3 
Investigator and Institutional Requirements 
  
Principle investigator and co‐investigators comply with institutional research procedures and 
policies. The study will be activated after approval by the IRB. 
Proprietary of MD Anderson Cancer  Center MDACC ID: 2019-0030 
NCT ID: NCT041324208 
Document Date: 7/28/2021


8 
 
5.4 
Study Calendar (Accrual process) 
  
Visits 
Activities 
Site/Person involved 
Initial clinic visit 
Determination of eligibility 
GU multidisciplinary center 
Imaging visit 
Standard of care Bone scan 
Diagnostic Imaging 
Imaging visit 
The standard of care CT abdomen 
Diagnostic Imaging 
Imaging visit 
The standard of care pelvic MRI with 
endorectal coil 
Diagnostic Imaging 
Imaging visit 
Research 18F‐fluciclovine PET CT 
Diagnostic Imaging 
  
5.5 
Pre‐test/study evaluation 
Patients with metastatic prostate cancer are seen and evaluated at genitourinary multidisciplinary 
care center of MDACC. Based on the past clinical volumes, we are expected to see 2‐4 metastatic 
prostate cancer patients per month. This center is staffed by clinical faculty from urology, medical 
oncology,  and  radiation  oncology  departments.  Before  enrollment,  patients  will  be  seen  in 
genitourinary  multidisciplinary  center  in  consultation  with  a  medical  oncologist,  urologist,  and 
radiation oncologist to ensure eligibility.  
 
5.6 
Registration Visit and Procedures  
Verification of eligibility criteria, and clinical consultation notes by DI research nurse. All patients will 
be scheduled to undergo standard of care laboratory studies and imaging workup that include PSA, 
bone scan, CT abdomen and mpPelvic MRI with the endorectal coil. Informed consent will be obtained 
by either by a qualified research personnel or research staff. 
 
5.7 
Baseline Imaging Visits  
Baseline bone scan, CT abdomen, mpPelvic MRI (or) 18F‐fluciclovine PET CT will be scheduled or 
completed within 30 days before initiation of SST. Please refer to Appendix C. for complete imaging 
protocols. 
  
5.8 
Post Systemic Therapy‐Imaging Visits  
Patients will return following 22‐28 weeks (+/‐ 4 weeks) of SST for follow‐up imaging studies which 
will include MDP Bone scan, CT abdomen, MP PELVIC MRI AND 18F‐FLUCICLOVINE PET CT. 
 
5.9 
Criteria for Removal from Study  
Subjects must be withdrawn from the study for the following reasons: 
5.9.1 
The patient withdraws consent 
5.9.2 
The patient cannot complete all imaging tests within 30 days of 
time frame. 
5.9.3 
Study completed 
 
5.10 
Innovation: 
This is to our knowledge the first study of using 18F‐fluciclovine PET CT in the assessment of 
therapy  response  in  prostate  cancer.  Although  glucose  metabolism  is  recognized  as  a  key 
metabolic pathway for imaging, amino acid metabolism is emerging as a promising pathway for 
Proprietary of MD Anderson Cancer  Center MDACC ID: 2019-0030 
NCT ID: NCT041324208 
Document Date: 7/28/2021


9 
 
tumor imaging.30,31 Recent studies with 18F‐Fluciclovinehave shown that this tracer can accurately 
detect prostate cancer and regional lymph node metastases with better specificity and sensitivity.32‐
34 18F‐fluciclovine have also been tried in breast cancer with positive results. A pilot study evaluated 
the ability of 18F‐fluciclovine avidity to determine neoadjuvant therapy response in 24 breast cancer 
patients, using histology after definitive surgical management as the gold standard.35 Changes in 18F‐
fluciclovine  avidity  strongly  correlated  with  the  percentage  of  reduction  of  tumor  seen  on 
pathology.35 Motivated by these prior studies, we propose to evaluate the ability of 18F‐fluciclovine 
avidity  to  determine  neoadjuvant  therapy  response  in  M1PCa.  In  addition  to  establishing  the 
importance of tumor response assessment with novel radio tracers, this study has the potential to 
combine with pelvic MRI and whole‐body MRI to study high risk and metastatic prostate cancer. 
Also, the knowledge gained from this research will be used to design and test the utility of PET‐MRI 
with novel tracers such as 18F‐fluciclovine and PSMA. The culmination of the pilot studies will be an 
extramural application to conduct a multicenter trial.  
 
5.11 
End of the Study information handling 
All collected information from participants will be destroyed, including patient identifiers. This 
information will be destroyed within 5 years from publication in accordance with UT MD Anderson  
Cancer Center policies.  
 
 
6.0 
Statistical Considerations 
  
Objectives, Endpoints, and Study Design 
 
The primary objective of this prospective study is to evaluate the ability of 18F Fluciclovine 
PET CT to determine the therapeutic response to SST. All eligible patients will be imaged by 18F 
Fluciclovine  PET  CT  before  and  after  treatment.  Treatment  responders  were  defined  as  the 
posttreatment PSA level <= 4.0 ng/mL, and >4.0 ng/mL for non‐responders. The primary endpoint 
is the percentage change of 18F‐fluciclovine SUVmax. Secondary endpoints include the size changes 
defined by conventional imaging; TBR; sensitivity, specificity, positive predictive value (PPV), and 
negative predictive value (NPV) when comparing 18 F Fluciclovine PET CT imaging findings with 
pathologic findings; progression free survival defined by PCWG2 criteria; and the types of metastatic 
progression sites. The accuracy of using the percentage change of 18F‐ Fluciclovine SUVmax to 
discriminate  treatment  responders  from  non‐responders  is  evaluated  using  Receiver  Operating 
Characteristic (ROC) curve analysis. 
 
 
Sample Size and Power Calculation 
We wish to enroll 41 evaluable patients. With an overall sample size of 41 and an estimated 
70% response rate, we expect approximately 28 responders and 13 non‐responders. With these 
numbers, we will have 83% power to detect a difference of 0.26 between the area under the ROC 
curve (AUC) under the null hypothesis of 0.50 and an AUC under the alternative hypothesis of 0.76 
using a two‐sided z‐test at a significance level of 0.05. Considering a drop‐out rate of 10%, the total 
sample size required is 45. 
 
Proprietary of MD Anderson Cancer  Center MDACC ID: 2019-0030 
NCT ID: NCT041324208 
Document Date: 7/28/2021


10 
 
Analysis Plan 
Patient characteristics and clinical outcomes will be summarized using frequencies, mean, standard 
deviation, median, and range. Accuracy of predicting responders using the percentage changes of 
SUVmax or the size changes by conventional imaging will be analyzed by ROC curves. AUC will be 
compared using the nonparametric method described by Delong (1988). Optimal cut‐ off points for 
dichotomizing the percentage changes of SUVmax or the size changes will be selected by maximizing 
the Youden's index. Dichotomized values will be compared using the McNemar's test. Sensitivity, 
specificity, PPV, and NPV to correlate dichotomized 18 F Fluciclovine PET CT imaging findings with 
pathologic findings will be estimated along with 95% confidence intervals. 
Kaplan‐Meier method will be used to estimate progression free survival (PFS). Log‐rank test will be 
used to compare PFS between imaging response groups. Frequencies will be estimated for different 
types of metastatic progression sites. Other statistical analyses will be carried out as appropriate. 
 
7.0 
Adverse Events; Safety Issues 
 
Adverse event reporting and safety issues will be reported as per the MDACC procedures and 
policies. In addition to reporting of Serious Adverse Events (SAEs) to the responsible IRB and Health 
Authority, the PI is required to promptly notify Blue Earth Diagnostics (BED) in the event of (SAEs) 
that occur following receipt of [18F]fluciclovine (whether or not related to study drug). 
Such SAEs must be reported within 24 hours of Principal Investigator or designee becoming aware 
of the event. All SAE information must be recorded and faxed or scanned and emailed to: 
 
Blue Earth Diagnostics SAE E mail: 
Drugsafety@pharsafer.com 
Tel: 
1 855 AXUMIN1 (1 855 298 6461) 
Fax: 
+44 (0) 1483 212178. 
 
If BED receives any individually identifiable health information collected or produced in the study, 
BED shall use and disclose only for the purpose of complying with applicable laws, provided that all 
such uses are disclosed in the IRB‐approved informed consent form. BED will use all reasonable 
efforts to protect the privacy and security of individually identifiable health information and will 
require its business partners to do so also. BED will not contact any study subjects, unless permitted 
by the informed consent form There are no expectations of BED contacting the participants. 
 
F18 Fluciclovine (Axumin) 
The recommended dose is 370 MBq (10 mCi) administered as an intravenous bolus injection. The 
(radiation absorbed) effective dose resulting from this dose of Axumin is 8 mSv. The clinical trial 
database for Axumin includes data from 877 subjects including 797 males diagnosed with prostate 
cancer. Most patients received a single administration of F18 fluciclovine; a small number of subjects 
(n = 50) received up to five administrations of the drug. The mean administered activity was 370 
MBq (range, 163 to 485 MBq). Adverse reactions were reported in ≤1% of subjects during clinical 
studies with F18 fluciclovine. The most common adverse reactions were injection site pain, injection 
site erythema and dysgeusia. 
 
 
 
 
Proprietary of MD Anderson Cancer  Center MDACC ID: 2019-0030 
NCT ID: NCT041324208 
Document Date: 7/28/2021


11 
 
8.0 
Ethical Considerations (Including Informed Consent) 
 
Informed consent and ethical consideration will be in compliance with MDACC procedures and 
policies. 
 
9.0 
Data Management; Administrative Issues 
Imaging data will be stored in MDACC PACS. Confidentiality of personal health information (PHI) will 
be maintained throughout the study. Data will be stored in password‐protected database maintained 
by research information system and technology service server at MDACC. The investigators do realize 
that a risk to patient PHI confidentiality exists whereby personal information could be accidentally be 
released, however, all necessary precautions will be taken to prevent this from happening. Unique 
patient identifier will be available only to the investigators for the study and will be kept in a password‐
protected database and locked file cabinet. Paper records (data forms, list of patient names, and 
unique  identifiers,  etc.)  will  be  kept  in  a  locked  file  cabinet  with  access  granted  only  to  study 
investigators. No identifying personal health information will be used in any publication from this 
study.  Collected  information  (including  patient  identifiers)  will  be  destroyed  within  5  years  after 
publication. The protected health information used in this study will not be reused or disclosed to any 
person or entity outside of the investigator nor will it be used for other research. 
 
10.0 
Budget 
Research staff support from DI‐Office of Clinical and Translational Research 
DICRC funding for scan time (PET/CT (CABI): $790/hr x 45 patients x 2 time points 
=$71,100) 
Blue  Earth  Diagnostics  (BED)  will  provide  the  dose  upon  completion  research  agreement  with 
MDACC (18F‐Fluciclovine: $6200/dose x 45 patients x 2 time points =$558,000) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Proprietary of MD Anderson Cancer  Center MDACC ID: 2019-0030 
NCT ID: NCT041324208 
Document Date: 7/28/2021


12 
 
11.0 
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