Clinical trial NCT01479348
Conditions: Head and Neck Neoplasms Lung Neoplasms Urinary Bladder Neoplasms Breast Neoplasms
Keywords: Imaging Radiopharmaceutical Safety Dosimetry Drug Distribution Cancer
Sponsor: National Cancer Institute (NCI)
Start date: 2011-11-01; Completion date: 2019-01-11
Enrollment: 5 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Background:

\- The drugs FdCyd (also called 5-fluoro-2'-deoxycytidine) and THU (also called tetrahydrouridine) are being used in a cancer treatment study. Not a lot is known about how FdCyd works in the body. Researchers want to look at a modified form of FdCyd using imaging studies to see how the drug reacts with the cancer. This study is not a treatment study. It is open only to people who are already on the FdCyd and THU cancer treatment study.

Objectives:

\- To study how FdCyd affects advanced cancer cells.

Eligibility:

\- Participants in National Cancer Institute study 09-C-0214.

Design:

* Participants will have two imaging studies, one before starting FdCyd and THU treatment and one after starting treatment.
* Participants will have the modified FdCyd, known as F-18 FdCyd, with a dose of THU. The doses will be followed by two imaging study scans and frequent blood samples.
* This procedure will be repeated at a later date, during the FdCyd and THU treatment period.
* Treatment will not be provided as part of this study. This is an imaging study protocol only....

Detailed description:
BACKGROUND:

\- In pre-clinical models, 5-fluoro-2-deoxycytidine (FdCyd), administered along with

tetrahydrouridine (THU; an inhibitor of cytidine/deoxycytidine deaminase), has shown superior anti-tumor activity as compared with 5-fluorouracil.

\- FdCyd can be phosphorylated to 5-fluoro-2-deoxycytidylate (FdCMP) by deoxycytidine

kinase and the nucleotide deaminated to FdUMP by deoxycytidylate (dCMP) deaminase.

The activity of dCMP deaminase is reported to be higher in human malignancies than in normal tissues, which may result in selective cytotoxicity.

* FdCyd is an inhibitor of deoxyribonucleic acid (DNA) methyltransferase and DNA methylation, resulting in reexpression of genes silenced by DNA hypermethylation. It is being evaluated in a phase II multihistology clinical trial at the Developmental Therapeutics Clinic, National Cancer Institute (NCI), Clinical Center, National Institutes of Health (NIH).
* While FdCyd + THU has shown preliminary evidence of activity in early phase trials not all patients show clinical response. The establishment of a radiolabeled form to image the biodistribution in vivo at baseline and during therapy may provide insight into the distribution of the therapeutic drug.
* The first step in the development of such an in vivo marker is to determine the

biodistribution and safety of the radiolabeled form.

OBJECTIVES:

* Determine the safety of \[F-18\]-5-fluoro-2'-deoxycytidine (FdCyd) administered intravenously with administration of tetrahydrouridine (THU).
* Estimate the radiation dosimetry of \[F-18\]-FdCyd in humans.

ELIGIBILITY:

* Only patients enrolled in NCI Phase II Study evaluating FdCyd with THU (NCI Protocol # 09-C-0214 (CTEP# 8351) or NCI Protocol #12-C-0066 (CTEP# 9127)) at the NIH Clinical Center will be eligible to participate in this study).
* Patients must have a target lesion greater than or equal to 10mm
* May not be pregnant or lactating; must be less than or equal to 350 lbs; and may not have known allergy to FdCyd or contraindications to positron emission tomography (PET)/computed tomography (CT) imaging.

DESIGN:

* There are two arms to this study
* The first arm will be patients enrolling in the therapeutic Phase II 5-FdCyd/THU study (NCI Protocol # 09-C-0214 (CTEP# 8351) in the NCI Developmental Therapeutics Clinic
* The second arm will be patients enrolling in the Phase I 5-FdCyd/THU study (NCI Protocol #12-C-0066 (CTEP# 9127)) in the NCI Developmental Therapeutics Clinic.
* Patients will undergo an initial \[F-18\]-FdCyd + THU PET/CT imaging prior to therapeutic dosing on study NCI Protocol # 09-C-0214 (CTEP# 8351) or NCI Protocol #12-C-0066 (CTEP# 9127). Repeat imaging will be performed while the patient is receiving FdCyd + THU therapy under the parent therapeutic protocol. This imaging must be completed 2-5 days after cycle start and at least 2 hours after a dose. Upon completion of repeat imaging, patients will be taken off this imaging study 24 hours after the last imaging session.

Arms: arm 1: \[F-18\]-5-fluoro-2'-deoxycytidine plus Tetrahydrouridine arm 2: \[F-18\]-5-fluoro-2'-deoxycytidine plus Tetrahydrouridine
Interventions: intervention 1: [F-18]-5-FLUORO-2'-DEOXYCYTIDINE intervention 2: Tetrahydrouridine intravenous (IV) intervention 3: Tetrahydrouridine (oral) intervention 4: Positron emission tomography (PET)/Computed tomography (CT)
Intervention descriptions: intervention 1: 18FdCyd radiotracer intervention 2: Total dose of THU = 350 mg/m\^2, IV intervention 3: Total dose of THU is 3000 mg, oral intervention 4: One prior CT and 3 sequential whole body PET

Protocol documents:
ICF_002.pdf: 
MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
INSTITUTE: 
National Cancer Institute 
STUDY NUMBER: 
12-C-0014 
PRINCIPAL INVESTIGATOR: 
Karen A. Kurdziel, M.D. 
STUDY TITLE:  
Phase 0 Trial of [F-18]-5-Fluoro-2'-Deoxycytidine with Tetrahydrouridine 
 
 
Continuing Review Approved by the IRB on 02/27/17 
Amendment Approved by the IRB on 03/18/15 (G) 
 
Date Sent to Web: 03/18/17  
Oral FdCyd + THU 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent (2) 
 
 
INTRODUCTION 
We invite you to take part in a research study at the National Institutes of Health (NIH). 
First, we want you to know that: 
Taking part in NIH research is entirely voluntary.  
You may choose not to take part, or you may withdraw from the study at any time.  In 
either case, you will not lose any benefits to which you are otherwise entitled.  However, 
to receive care at the NIH, you must be taking part in a study or be under evaluation for 
study participation. 
You may receive no benefit from taking part.  The research may give us knowledge that 
may help people in the future. 
Second, some people have personal, religious or ethical beliefs that may limit the kinds of 
medical or research treatments they would want to receive (such as blood transfusions).  If you 
have such beliefs, please discuss them with your NIH doctors or research team before you agree 
to the study. 
Now we will describe this research study.  Before you decide to take part, please take as much 
time as you need to ask any questions and discuss this study with anyone at NIH, or with family, 
friends or your personal physician or other health professional.   
Why is this study being done?  
There is a treatment research study being done in patients with advanced cancer in which two 
experimental drugs are being given, FdCyd (also called 5-fluoro-2’-deoxcytidine), and THU 
(also called tetrahydrouridine).  You have agreed to participate in that treatment study.  There is 
not a lot of information known about how FdCyd works in the body.  Therefore, this study is 
being done to test if PET (Positron Emission Tomography) imaging with F-18 FdCyd (a 
radiolabeled version of the experimental treatment drug FdCyd) will give us information about 
how much of the treatment drug your tumor is taking up.  This will help us understand how 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0014 
CONTINUATION: page 2 of 10 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
FdCyd works in the body to fight cancer.  This is not a treatment study; participating in this 
study will not help in the treatment of your cancer.   
Why are you being asked to take part in this study? 
You are being asked to participate because you are enrolled in the treatment protocol entitled: 
Phase I Trial of Oral 5- Fluoro-2’-Deoxycytidine With Oral Tetrahydrouridine in Patients With 
Advanced Solid Tumors NCI #12-C-0066/CTEP #9127 being performed in the Medical 
Oncology Branch, NCI/NIH.  Throughout this consent document, the treatment protocol will be 
referred to as or 12-C-0066/9127. 
How many people will take part in this Study?  
We expect to enroll 10-20 patients in this experimental imaging study. 
Description of Research Study 
Participation in this study involves undergoing 2 PET/CT imaging sessions, one before starting 
your treatment on 12-C-0066/9127, and one after you start treatment on 12-C-0066/9127.  The 
reason 2 imaging sessions are being done is to see if the quality of the images gets better after 
you have some of the treatment FdCyd in your body. 
What will happen if you take part in this research study?   
Before you begin the imaging study 
This study is being performed in conjunction with protocol 12-C-0066/9127 that you have 
enrolled in.  If you chose to participate in this imaging study, we will first make sure you are 
eligible.  To make sure it is safe to undergo the scans we will ask you some questions about your 
medical history and any allergies, if you are a woman able to get pregnant, we will also perform 
a pregnancy test (blood or urine) to make sure you are not pregnant, and ask you to sign this 
informed consent.  
During this imaging study 
Before beginning your first therapy dose of FdCyd on protocol 12-C-0066/9127, you will receive 
a dose of Tetrahydrouridine (THU) oral solution, a compound that blocks the enzyme which 
breaks down FdCyd, by mouth.  THU should be taken on an empty stomach at least 1 hour 
before or 2 hours after a meal, and 30 minutes before taking FdCyd.  Tetrahydrouridine oral 
solution will be mixed with 2-3 ounces of an acidic juice (for example, orange juice, apple juice 
or lemonade) immediately prior to dosing. There are no known side effects to THU at the dose 
levels you will be given, and this additional dose will NOT affect your future treatment with 
FdCyd + THU.  You will also receive a small amount of F-18 FdCyd.  This is a radiolabeled 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0014 
CONTINUATION: page 3 of 10 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
version of the therapy drug you will receive on12-C-0066/9127.  The F-18 radiolabel acts as a 
tag, and lets us see on the PET/CT scan where the FdCyd goes in your body.   
The F-18 FdCyd is given into your IV over about 1-3 minutes.  You should not feel anything 
during this time.  After you are given the F-18 FdCyd you will have a PET/CT scan.  You will 
need to lie still on your back on the scanning table for up to 75 minutes for the first scan and ~35 
minutes for an additional scan.  The PET/CT scan consists of a “low dose transmission” CT 
(sometimes called a CAT scan), followed by PET imaging.   
This imaging procedure will be repeated on a separate day, after receiving your therapeutic dose 
of FdCyd + THU by mouth on protocol 12-C-0066/9127. Repeat imaging will be performed 2-5 
days after the initiation of FdCyd + THU therapy and at least 2 hours after dosing. 
When you are finished the Imaging Sessions 
When you are finished with each PET/CT imaging session, there are no restrictions on your diet 
or activity as a result of this protocol.  After you have completed the second imaging session you 
will be taken off this imaging study and will continue your participation on protocol 12-C-
0066/9127.  We may use the information from the protocol 12-C-0066/9127; we will compare 
how well the F-18 FdCyd went into the tumor with your tumor response after receiving the 
experimental treatment agents.  
What does this study involve? 
This study involves two F-18 FdCyd PET/CT imaging sessions, one performed before receiving 
a treatment dose of FdCyd + THU, and a second performed while receiving a treatment dose of 
FdCyd + THU as prescribed by the Phase 1 protocol.  You will be required to have an IV 
catheter put into a vein in your arm for each PET/CT imaging study.  You will need to lie still on 
the PET scan table for up to 120 minutes during the imaging session.   
If you are a woman who is breast feeding or pregnant, you may not take part in the study because 
we don’t know how this medicine would affect your baby or your unborn child.  
Alternative Approaches or Treatments 
This is not a treatment study.  This study can only be performed in conjunction with your 
participation on protocol 12-C-0066/9127.  The alternative is to not participate.  If you choose 
not to participate in this imaging study, it will not affect your ability to participate in protocol 12-
C-0066/9127. 
What other choices do I have if I do not take part in this study?  
As this is not a treatment study, you can choose not to participate.   


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0014 
CONTINUATION: page 4 of 10 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
Will my medical information be kept private? 
We will do our best to make sure that the personal information in your medical record will be 
kept private.  However, we cannot guarantee total privacy.  Your personal information may be 
given out if required by law.  If information from this study is published or presented at scientific 
meetings, your name and other personal information will not be used. 
Organizations that may look at and/or copy your medical records for research, quality assurance, 
and data analysis include: 
• The National Cancer Institute (NCI) and other government agencies, like the Food and 
Drug Administration (FDA), involved in keeping research safe for people. 
Risks or Discomforts of Participation 
What side effects or risks can I expect from being in this study?  
Risks of FdCyd/THU 
 
COMMON, SOME MAY BE SERIOUS 
In 100 people receiving FdCyd/THU, more than 20 and up to 100 may have: 
• Anemia which may require blood transfusion 
• Diarrhea, nausea, vomiting 
• Tiredness 
• Bruising, bleeding 
• Infection, especially when white blood cell count is low 
• Loss of appetite 
 
OCCASIONAL, SOME MAY BE SERIOUS   
In 100 people receiving FdCyd/THU, from 4 to 20 may have: 
• Abnormal heartbeat 
• Bloating, constipation, heartburn, passing gas 
• Pain 
• Dry mouth, skin 
• Sores in mouth which may cause difficulty swallowing 
• Chills, fever 
• Swelling of arms, legs 
• Weight loss 
• Dehydration 
• Muscle weakness 
• Dizziness, headache 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0014 
CONTINUATION: page 5 of 10 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
• Changes in taste 
• Numbness, tingling or pain of the arms and legs 
• Cough, shortness of breath 
• Nose bleed 
• Hair loss, itching, rash 
• Increased sweating 
• Redness, pain or peeling of the palms and soles 
• Low blood pressure which may cause feeling faint 
o  
Risks of FdCyd 
No adverse effects are expected from the small amount of F-18 FdCyd that will be administered 
under this protocol (for PET/CT imaging).  THU has no expected side effects at the dose used in 
this study and may increase the risk of experiencing FdCyd side effects.  Even though we do not 
anticipate adverse side effects, you should tell the doctors or nurses supervising the scan of any 
discomfort. 
Potential discomforts from the IV and injection of the radiotracer include 
o Mild pain and possible bruising at the injection site  
o Discomfort from lying on a hard surface for about 75 minutes 
o Infection at the IV site or infection in the blood  
o Leaking of the dose of F-18 FdCyd into the skin and tissue around the IV 
o Allergic reaction 
o Vasovagal reaction, a lowered blood pressure and heart rate during the IV insertion  
Risks of Radiation 
F-18 FdCyd is a radioactive tracer and you will receive a small amount radiation exposure that 
you would not otherwise receive.  Please note that this radiation exposure is not necessary for 
your medical care and is for research purposes only.  
Using the standard way of describing radiation dose, from participating in this study and 
undergoing a total of two F-18 FdCyd PET/CT imaging sessions (including radiation from the F-
18 FdCyd injection and low dose transmission scans), the amount of radiation exposure you will 
receive is equal to a uniform whole-body exposure of 3.5 rem, although each organ will receive a 
different dose.  This calculated value is known as the “effective dose” and is used to relate the 
dose received by each organ to a single value.  For comparison, the average person in the United 
States receives a radiation exposure of 0.3 rem per year from natural background sources, such 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0014 
CONTINUATION: page 6 of 10 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
as from the sun, outer space, and from radioactive materials that are found naturally in the earth’s 
air and soil.  The dose that you will receive from this research study is about the same amount 
you would normally receive in 11.7 years from these natural sources. The organs receiving the 
highest doses are the urinary bladder wall (15.3 rad), the surfaces of the bones (4.15 rads), and 
the liver (4.15 rads). 
The effects of radiation exposure on humans have been studied for over 60 years.  In fact, these 
studies are the most extensive ever done of any potentially harmful agent that could affect 
humans.  In all these studies, no harmful effects were ever observed from the levels of radiation 
you will receive by taking part in this research study.  However, scientists disagree on whether 
radiation doses at these levels are harmful.  Even though no effects have been observed, some 
scientists believe that radiation can be harmful at any dose - even low doses such as those 
received during this research.  
If you would like more information about radiation and examples of exposure levels from other 
sources, please ask the investigator for a copy of the pamphlet called, An Introduction to 
Radiation for NIH Research Subjects. Please tell your doctor if you have taken part in other 
research studies or received any medical care at the NIH or other places/hospitals that used 
radiation.  This way we can make sure that you will not receive too much radiation.  Consider x-
rays taken in radiology departments, cardiac catheterization, and fluoroscopy as well as nuclear 
medicine scans in which radioactive materials were injected into your body. 
When the medication is put through a vein in your arm, you may experience a moment of pain.  
In addition, there is the discomfort of having the catheter taped to your arm.  Other risks include 
bleeding, bruising, temporary clotting of the vein, and infection.  
Potential Benefits of Participation 
Are there benefits to taking part in this study?  
As this is NOT a treatment protocol, you will not to have any direct benefits; however, the result 
of this study may help doctor’s better understand how and how much FdCyd enters tumors, 
which may benefit other patients in the future who have cancer.   
Research Subject’s Rights 
What are the costs of taking part in this study?  
Participation in this research study is voluntary and you can withdraw at any time.  We 
encourage you to ask questions so you can make the most informed decisions during your 
participation in this study.  Refusal to participate will not result in penalty or less benefits to 
which you are otherwise entitled.  


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0014 
CONTINUATION: page 7 of 10 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
It is important to stress that being in this protocol does not promise long-term medical care at the 
NIH Clinical Center.  If there is no further research study that is suitable for you and your state 
of disease, or if you are not currently on another research study, you will be returned to the care 
of your referring doctor or institution, or alternative sources of care closer to your home.  If you 
have any questions about your treatment in this protocol at NIH, you can contact the Principal 
Investigator, Dr. Karen A. Kurdziel (301-443-0622) or the patient care representative (301-496-
2626).  
If you choose to take part in the study, the following will apply, in keeping with the NIH policy: 
• 
Medicines that are not part of the study treatment will not be provided or 
paid for by the Clinical Center, NIH. 
• 
Once you have completed taking part in the study, medical care will no 
longer be provided by the Clinical Center, NIH. 
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. 
Stopping This Study 
Your doctor may decide to stop your participation in this study for the following reasons: 
• if he/she believes that it is in your best interest 
• if you are no longer participating in protocol 12-C-0066/9127 
• if you have side effects from the imaging sessions that your doctor thinks are too severe 
• if the imaging study is stopped for any reason. 
In this case, you will be informed of the reason therapy is being stopped. 
You can stop taking part in the study at any time. However, if you decide to stop taking part in 
the study, we would like you to talk to the study doctor and your regular doctor first. 
Conflict of Interest 
The National Institutes of Health (NIH) reviews NIH staff researchers at least yearly for conflicts 
of interest.  This process is detailed in a Protocol Review Guide.  You may ask your research 
team for a copy of the Protocol Review Guide or for more information.  Members of the research 
team who do not work for NIH are expected to follow these guidelines but they do not need to 
report their personal finances to the NIH. 
 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0014 
CONTINUATION: page 8 of 10 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
Members of the research team working on this study may have up to $15,000 of stock in the 
companies that make products used in this study.  This is allowed under federal rules and is not a 
conflict of interest.  
 


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
STUDY NUMBER: 12-C-0014 
CONTINUATION: page 9 of 10 pages 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
(Continuation Sheet) 
• 
Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
 
File in Section 4:  Protocol Consent 
 
 
OTHER PERTINENT INFORMATION 
1. 
Confidentiality.  When results of an NIH research study are reported in medical journals 
or at scientific meetings, the people who take part are not named and identified.  In most cases, 
the NIH will not release any information about your research involvement without your written 
permission.  However, if you sign a release of information form, for example, for an insurance 
company, the NIH will give the insurance company information from your medical record.  This 
information might affect (either favorably or unfavorably) the willingness of the insurance 
company to sell you insurance. 
The Federal Privacy Act protects the confidentiality of your NIH medical records.  However, you 
should know that the Act allows release of some information from your medical record without 
your permission, for example, if it is required by the Food and Drug Administration (FDA), 
members of Congress, law enforcement officials, or authorized hospital accreditation 
organizations. 
2. 
Policy Regarding Research-Related Injuries.  The Clinical Center will provide short-
term medical care for any injury resulting from your participation in research here.  In general, 
no long-term medical care or financial compensation for research-related injuries will be 
provided by the National Institutes of Health, the Clinical Center, or the Federal Government.  
However, you have the right to pursue legal remedy if you believe that your injury justifies such 
action. 
3. 
Payments.  The amount of payment to research volunteers is guided by the National 
Institutes of Health policies.  In general, patients are not paid for taking part in research studies at 
the National Institutes of Health.  Reimbursement of travel and subsistence will be offered 
consistent with NIH guidelines. 
4. 
Problems or Questions.  If you have any problems or questions about this study, or 
about your rights as a research participant, or about any research-related injury, contact the 
Principal Investigator, Karen A. Kurdziel, M.D., Building 10, Room B3B403, Telephone:  301-
443-0622. You may also call the Clinical Center Patient Representative at (301) 496-2626.  
5. 
Consent Document.  Please keep a copy of this document in case you want to read it 
again.


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
STUDY NUMBER: 12-C-0014 
CONTINUATION: page 10 of 10 pages 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
(Continuation Sheet) 
• 
Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
 
File in Section 4:  Protocol Consent 
 
 
 
COMPLETE APPROPRIATE ITEM(S) BELOW: 
A. Adult Patient’s Consent 
B. Parent’s Permission for Minor Patient. 
I have read the explanation about this study 
and have been given the opportunity to discuss 
it and to ask questions.  I hereby consent to 
take part in this study. 
I have read the explanation about this study 
and have been given the opportunity to discuss 
it and to ask questions.  I hereby give 
permission for my child to take part in this 
study.   
(Attach NIH 2514-2, Minor’s Assent, if 
applicable.) 
 
  
  
 
 
 
Signature of Adult Patient/ 
Legal Representative 
Date 
Signature of Parent(s)/ Guardian Date 
 
 
Print Name 
 
 
Print Name 
C. Child’s Verbal Assent (If Applicable) 
The information in the above consent was described to my child and my child agrees to 
participate in the study. 
 
  
  
 
Signature of Parent(s)/Guardian 
Date 
Print Name 
THIS CONSENT DOCUMENT HAS BEEN APPROVED FOR USE  
FROM FEBRUARY 27, 2017 THROUGH FEBRUARY 26, 2018. 
 
 
 
 
 
 
 
 
Signature of Investigator 
Date 
Signature of Witness 
Date 
 
 
Print Name 
 
 
Print Name 
 

Prot_SAP_000.pdf: 
Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
Abbreviated Title:  [F-18]-FdCyd Imaging
NCI Protocol #: 8865
Local Protocol #: 12-C-0014
Amendment: G
CTEP Protocol #: 8865
Title: Phase 0 Trial of [F-18]-5-Fluoro-2'-Deoxycytidine with Tetrahydrouridine
Principal Investigator:   
Karen A. Kurdziel, MD, 
Molecular Imaging Program (MIP)/CCR/NCI 
Building 10/ B3B403
10 Center Drive
Bethesda, MD 20892
Tel: 301-443-0622
kurdziek@mail.nih.gov
Associate Investigators:
Alice Chen, M.D. 
DTC/ NCI
31 Center Drive
Bldg 31, Room 3A44
Bethesda, MD 20892
Tel: 301-496-4291
Fax: 301-402-0172
chenali@mail.nih.gov
Peter L. Choyke, M.D.
MIP/CCR/NCI
Building 10/1B40
Bethesda, MD 20892
Tel: 301-451-4220
Fax: 301-402-3191
pchoyke@nih.gov
James H. Doroshow, M.D.
NCI/DCTD/OD
9000 Rockville Pike, Building 10/12N226
Bethesda, MD 20892
Tel: 301-496-4291
doroshoj@mail.nih.gov
Maria Liza Lindenberg, M.D.
MIP, CCR/NCI
Bldg 10/ RMB3B403 
Bethesda, MD 20892
301-443-0604
lindenbergml@mail.nih.gov
Responsible Research Nurse: 
Yolanda McKinney, RN
Office of the Clinical Director (OCD), CCR/NCI
Building 10/ Room B3B69E
Page 1 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
Bethesda, MD 20892
301-443-6913
ymckinney@mail.nih.gov
Statistician:
Joanna H. Shih, Ph.D.
Biometric Research Branch, DCTD/ NCI
9609 Medical Center Drive Room 4W230
Bethesda, MD 20850-9735
Phone: 240-276-6035
Fax: 240-276-7888
Jshih@mail.nih.gov
NCI Supplied Investigational Agents:    
Drug Name:
[F-18]-FdCyd Imaging (NSC 755309), 
Tetrahydrouridine (NSC 112907)
IND Number:
105843
Sponsor:
CTEP
Identifying words: Imaging, radiopharmaceutical, safety, dosimetry, drug distribution
Page 2 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
PRÉCIS
Background: 
x
In pre-clinical models, 5-fluoro-2’-deoxycytidine (FdCyd), administered along with 
tetrahydrouridine (THU; an inhibitor of cytidine/deoxycytidine deaminase), has shown 
superior anti-tumor activity as compared with 5-fluorouracil.
x
FdCyd can be phosphorylated to 5-fluoro-2’-deoxycytidylate (FdCMP) by deoxycytidine 
kinase and the nucleotide deaminated to FdUMP by deoxycytidylate (dCMP) deaminase. 
The activity of dCMP deaminase is reported to be higher in human malignancies than in 
normal tissues, which may result in selective cytotoxicity.
x
FdCyd is an inhibitor of DNA methyltransferase and DNA methylation, resulting in re-
expression of genes silenced by DNA hypermethylation. It is being evaluated in a phase 
II multihistology clinical trial at the Developmental Therapeutics Clinic, NCI, Clinical 
Center, NIH.
x
While FdCyd + THU has shown preliminary evidence of activity in early phase trials not 
all patients show clinical response.  The establishment of a radiolabeled form to image 
the biodistribution in vivo at baseline and during therapy may provide insight into the 
distribution of the therapeutic drug.
x
The first step in the development of such an in vivo marker is to determine the 
biodistribution and safety of the radiolabeled form.
Objectives:
x
Determine the safety of [F-18]-5-fluoro-2'-deoxycytidine (FdCyd) administered 
intravenously with administration of tetrahydrouridine (THU).
x
Estimate the radiation dosimetry of [F-18]-FdCyd in humans.
Eligibility:
x
Only patients enrolled in NCI Phase II Study evaluating FdCyd with THU (NCI Protocol 
# 09-C-0214 (CTEP# 8351) or NCI Protocol #12-C-0066 (CTEP# 9127)) at the NIH 
Clinical Center will be eligible to participate in this study).
x
Patients must have a target lesion  10mm
x
0D\QRWEHSUHJQDQWRUODFWDWLQJPXVWEH 350 lbs; and may not have known allergy to 
FdCyd or contraindications to PET/CT imaging.
Design:
x
There are two arms to this study
o
The first arm will be patients enrolling in the therapeutic Phase II 5-FdCyd/THU 
study (NCI Protocol # 09-C-0214 (CTEP# 8351) in the NCI Developmental 
Therapeutics Clinic
o
The second arm will be patients enrolling in the Phase I 5-FdCyd/THU study
(NCI Protocol #12-C-0066 (CTEP# 9127)) in the NCI Developmental 
Therapeutics Clinic.
x
Patients will undergo an initial [F-18]-FdCyd + THU PET/CT imaging prior to 
therapeutic dosing on study NCI Protocol # 09-C-0214 (CTEP# 8351) or NCI Protocol 
Page 3 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
#12-C-0066 (CTEP# 9127).  Repeat imaging will be performed while the patient is 
receiving FdCyd + THU therapy under the parent therapeutic protocol. This imaging 
must be completed 2-5 days after cycle start and at least 2 hours after a dose. Upon 
completion of repeat imaging, patients will be taken off this imaging study 24 hours after 
the last imaging session.
Page 4 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
TABLE OF CONTENTS
Précis............................................................................................................................................... 3 
TABLE OF CONTENTS................................................................................................................ 5 
1 
INTRODUCTION .................................................................................................................. 7 
1.1 
Study Objectives .............................................................................................................. 7 
2 
Background and Rationale:..................................................................................................... 7 
2.1 
[F-18]-5-Fluoro-2'-deoxycytidine (FdCyd)...................................................................... 8 
2.2 
Tetrahydrouridine (THU)............................................................................................... 12 
2.3 
Rationale......................................................................................................................... 12 
3 
Patient Selection.................................................................................................................... 13 
3.1 
Eligibility Criteria .......................................................................................................... 13 
3.2 
Screening Evaluation...................................................................................................... 14 
3.3 
Inclusion of Women and Minorities............................................................................... 14 
4 
Registration Procedures ........................................................................................................ 14 
5 
STUDY IMPLEMENTATION ............................................................................................ 14 
5.1 
Study Design .................................................................................................................. 14 
5.2 
Study Schema................................................................................................................. 15 
5.3 
Stopping Rules ............................................................................................................... 16 
5.4 
CTEP IND Agent Administration.................................................................................. 17 
5.5 
General Concomitant Medication and Supportive Care Guidelines .............................. 18 
5.6 
Duration of Participation................................................................................................ 18 
5.7 
Dosing Delays/Dose Modifications ............................................................................... 18 
5.8 
Criteria for Removal from Study ................................................................................... 18 
6 
ADVERSE EVENTS:  LIST AND REPORTING REQUIREMENTS ............................... 18 
6.1 
Comprehensive Adverse Events & Potential Risks Lists (CAEPR) for 5-Fluoro-2'-
deoxycytidine (FdCyd, NSC 48006) with Tetrahydrouridine (THU, NSC 112907)................ 19 
6.2 
Adverse Event Characteristics ....................................................................................... 22 
6.3 
Expedited Adverse Event Reporting.............................................................................. 24 
6.4 
Protocol-Specific Expedited Adverse Event Reporting Exclusions .............................. 26 
6.5 
Routine Adverse Event Reporting.................................................................................. 26 
6.6 
Secondary AML/MDS ................................................................................................... 26 
6.7 
NCI-IRB Reporting........................................................................................................ 26 
7 
Pharmaceutical InfoRmation ................................................................................................ 27 
Page 5 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
7.1 
[F-18]-5-Fluoro-2'-deoxycytidine (FdCyd) NSC# 755309 ............................................ 27 
7.2 
Tetrahydrouridine (THU) (NSC 112907) ...................................................................... 28 
8 
Study Calendar...................................................................................................................... 31 
9 
Measurement of Effect: Image Analysis............................................................................... 31 
9.1 
Tumor evaluation ........................................................................................................... 31 
9.2 
Dosimetry Estimates ...................................................................................................... 32 
10 DATA Reporting / Regulatory Considerations..................................................................... 33 
10.1 
Data Collection........................................................................................................... 33 
10.2 
Data Monitoring ......................................................................................................... 33 
10.3 
Sample Storage, Tracking and Disposition ................................................................ 33 
11 STATISTICAL SECTION ................................................................................................... 33 
12 HUMAN SUBJECTS PROTECTIONS ............................................................................... 34 
12.1 
Rationale For Subject Selection ................................................................................. 34 
12.2 
Participation of Children ............................................................................................ 34 
12.3 
Evaluation of Benefits and Risks/Discomforts........................................................... 34 
12.4 
Consent and Assent Process and Documentation....................................................... 34 
13 REFERENCES ..................................................................................................................... 36 
14 Appendix 1: PREPARATION OF TETRAHYDROURIDINE (THU) TUBES.................. 38 
15 Appendix 2:  PERFORMANCE STATUS SCALES/SCORES ECOG or Zubrod scale 
Karnofsky score ............................................................................................................................ 39 
Page 6 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
1
INTRODUCTION
1.1
Study Objectives
1.1.1
Primary Objectives:
1.1.1.1
To determine the safety of [F-18]-5-fluoro-2'-deoxycytidine (FdCyd) administered 
intravenously with administration of tetrahydrouridine (THU) 
1.1.1.2
To estimate the radiation dosimetry of [F-18]-FdCyd in humans
1.1.2
Secondary Objectives:
1.1.2.1
To evaluate the pharmacokinetics of [F-18]-FdCyd via PET/CT 
1.1.2.2
To evaluate the distribution of FdCyd in tumorous and non-tumorous tissue
2
BACKGROUND AND RATIONALE:
5-fluoro-2’-deoxycytidine (FdCyd), administered along with tetrahydrouridine (THU; an 
inhibitor of cytidine/deoxycytidine deaminase), has shown superior anti-tumor activity as 
compared with 5-fluorouracil in pre-clinical models. Following administration of FdCyd, it is 
phosphorylated to 5-fluoro-2’-deoxycytidylate (FdCMP) by deoxycytidine kinase and the 
nucleotide deaminated to FdUMP by deoxycytidylate (dCMP) deaminase. The activity of dCMP 
deaminase is reported to be higher in human malignancies than in normal tissues, which may 
result in selective cytotoxicity. FdCyd is an inhibitor of DNA methyltransferase (DNMT) and 
DNA methylation, resulting in re-expression of genes silenced by DNA hypermethylation. Co-
administration of THU inhibits the metabolism of the parent FdCyd allowing it to circulate in its
original form, and intracellularly inhibit DNMT.  
The process of intracellular activation creates a charged species that is trapped inside the cell, 
and since the sensitivity is directly linked to the amount of activated drug that collects inside the 
cell, the drug itself has very favorable properties as a probe for tumor localization. The 
biomolecular literature indicates that the pathways for intracellular uptake, retention, and 
activation of 5FdC to nucleotides are subject to substantial variation in human tumors. Thus, 
information that could guide the selection of tumors that were more likely to be sensitive or 
resistant to 5FdCyd would potentially aid in its development.
Figure 1: NSC 48006, 5-F-deoxycytidine (5FdC) and Tetrahydrouridine (THU)
In general, noninvasive imaging of many pyrimidines has been hindered by the high amounts of 
background radioactivity produced by catabolism.  In the proposed study, co-administration of 
THU inhibits the catabolism of FdCyd reducing the background. 
Page 7 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
Figure 2: Metabolism of 5-fluoro-2’-deoxycytidine (FdCyd). Metabolites are 5-fluoro-2’-
deoxyuridine (FdUrd), 5-fluorocytosine (FC), 5-fluorouracil (FU), 5-fluorouridine (FUrd), 
and 5-fluorouridine mono-phosphate (FUMP). Tetrahydrouridine (THU) blocks the 
conversion of FdCyd to FdUrd by cytidine deaminase. Solid arrows represent metabolic 
pathways, open arrows represent drug effects (26).
2.1
[F-18]-5-Fluoro-2'-deoxycytidine (FdCyd)
2.1.1
Chemistry and Pharmacology:
FdCyd [C9H12FN3O4, mol. wtİȜPD[ LQ0+&O@LVD
fluoropyrimidine antimetabolite.  The cytotoxicity of FdCyd in culture is associated with 
inhibition of thymidylate synthase (12) and with incorporation into DNA (14).  In addition to 
being activated by dCyd Kinase (12), FdCyd is a substrate for Cyd/dCyd deaminase (24).  The 
metabolism of the deamination product, 5-FdU, has been well characterized (5). No direct 
pharmacokinetic studies of FdCyd have been reported.  By similarity to other analogs of 
deoxycytidine, FdCyd is expected to have a very short mean residence time unless an effective 
inhibitor of Cyd/dCyd deaminase, e.g., THU, is co-administered. 
2.1.2
Formulation and Stability: 
[F-18]-5-Fluoro-2'-deoxycytidine (FdCyd) Injection is formulated in sterile saline and is 
manufactured by the University of Pennsylvania, Philadelphia, PA.
Page 8 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
The radioactive dose is 5 mCi or less at the time of administration.
2.1.3
Toxicity: 
The quantity of [F-18]-FdCyd required for imaging is a microdose, and no toxicity is expected to 
be observed from the radiopharmaceutical.  However, patients will be observed particularly for 
the toxicities noted in the animal and therapeutic studies.  Based on the results of animal studies
(1), the toxicities of a therapeutic dose of FdCyd are expected to be similar to those produced by 
5-FdU and 5-FU, including neutropenia, mucositis, diarrhea, nausea and vomiting.  This drug 
should be considered to have potential carcinogenic and teratogenic effects based on the 
carcinogenicity/teratogenicity of related drugs and on the teratogenic effects of FdCyd that have 
been reported in mice, including vertebral malformations, supernumerary limbs, and limb 
malformations. 
During a Phase 1 therapeutic trial, additional toxicities possibly related to the FdCyd/THU were 
noted at FdCyd doses of 40 mg/m2/day 5 days a week for 2 weeks and above.  These toxicities 
included electrolyte imbalances not immediately corrected with supplementation, elevated liver 
function tests, and anemia.  None of the toxicities to date have had unresolved sequelae. 
2.1.4
Pre-clinical Biodistribution for [18F]-FdCyd:
Radiation dosimetry estimates were based on rodent studies performed by IBA (the manufacturer 
of this radiotracer) under an NCI contract and the results are included in Table 1, and sample 
images are included in Figure 3. Briefly, the estimated ED for the doses proposed in this study 
(5 mCi FdCyd) and transmission CT for a total of 2 imaging sessions) is 3.52 rem and the organs 
receiving the highest doses are the urinary bladder, liver, and kidneys.
Table 1
Radiation Dosimetry and Effective Dose Calculation
Material:
F-18 FdCyd
Dose/study
5
mCi
Subject Age:
ADULT
DOSE/STUDY
Organ
rad/mCi
rads
Adrenals
0.019
0.0955
Brain
0.001
0.0065
Breasts
0.004
0.01945
Esophagus 1
0.004
0.02085
Gallbladder Wall
0.031
0.154
Lower Large Intestine
0.038
0.192
Page 9 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
Radiation Dosimetry and Effective Dose Calculation
Material:
F-18 FdCyd
Dose/study
5
mCi
Subject Age:
ADULT
DOSE/STUDY
Organ
rad/mCi
rads
Small Intestine
0.020
0.0975
Stomach
0.009
0.0459
Upper Large Intestine
0.018
0.091
Colon 2
0.027
0.13443
Heart Wall
0.009
0.04625
Kidney
0.125
0.625
Liver
0.145
0.725
Lungs
0.020
0.1015
Muscle
0.016
0.079
Ovaries
0.036
0.182
Pancreas
0.016
0.081
Red Marrow 3
0.011
0.0555
Bone Surfaces 4
0.007
0.03645
Skin
0.006
0.02845
Spleen
0.008
0.04165
Testes
0.026
0.1275
Thymus
0.004
0.02085
Thyroid
0.002
0.0109
Urinary Bladder Wall
1.250
6.25
Page 10 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
Radiation Dosimetry and Effective Dose Calculation
Material:
F-18 FdCyd
Dose/study
5
mCi
Subject Age:
ADULT
DOSE/STUDY
Organ
rad/mCi
rads
Uterus
0.081
0.405
Salivary Glands3
0.002
0.0109
REMAINDER AVE
0.036
0.180544444
EFFECTIVE DOSE (rem)
4.42E-01
Notes
1 Since no dose is explicitly tabulated for esophagus, thymus dose is used (as per ICRP 80)
2 Colon Dose estimated by [0.57 (DoseULI) + 0.43 (DoseLLI)] (as per ICRP 80).
3Salivary gland dose is set equal to the thyroid dose
Source: IBA, manufacturer
Figure 3:
Page 11 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
a) Typical image of the kidneys after 4 hours (MIP, Axial, sagittal, and coronal at the level 
of the kidneys)
b) Same mouse, typical image of the liver at 4 hours (MIP, Axial, sagittal, and coronal at the 
level of the liver)
As 18F FdCyd is chemically identical to the therapeutic drug FdCyd, the preclinical toxicity data 
from the therapeutic agent is the same as that for this imaging agent. 
2.2
Tetrahydrouridine (THU)
2.2.1
Chemistry and Pharmacology: 
THU [C9H16N2O6, mol. wt. 248.2] is an effective inhibitor of Cyd/dCyd deaminase in animals 
and humans (18, 19). It has a plasma half-life in humans of approximately one hour (19).
2.2.2
Toxicity: 
At an average total dose of 750 mg/kg (10 to 50 mg/kg/day for up to 23 days), THU alone was
not toxic to humans; THU potentiated the toxicity of araC, but no toxicity occurred with the 
combination that would not have been expected from araC given alone at an equitoxic dose (20). 
THU has been administered by three-hour infusion in conjunction with araC without producing 
toxicities other than those expected from the araC (22).
2.3
Rationale 
FdCyd + THU has shown preliminary evidence of clinical benefit in early phase trial and is 
being evaluated in a phase II trial for the treatment of refractory head and neck, breast, non-small 
cell lung and transitional cell carcinoma as part of the CTEP 8351 (NCI Protocol # 09-C-0214) 
trial. However, the clinical benefit so far has been observed in a minority of patients making it 
important to design a strategy for patient selection. By establishing a method to evaluate the
biodistribution of the drug and its ability to be taken up by the tumor cells, achieving 
intracellular therapeutic concentrations may provide insight into these variable responses.
Page 12 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
Currently an oral form of 5-fluoro-2’-deoxycytidine with oral tetrahydrouridine is being tested in 
a phase I study (CTEP# 9127, NCI Protocol 12-C-0066) in patients with advanced solid tumors. 
The goal of the protocol is to achieve oral FdCyd plasma concentrations similar to IV 
administration concentrations. Protocol 12-C-006 (CTEP 9127) is being performed because one
of the main limitations of the IV regimen is the number of days and duration of drug 
administration in each cycle, which requires multiple patient visits. An oral formulation would 
improve feasibility and compliance; therefore allowing an additional pool of patients that can 
participate in this study.
The proposed study with the establishment of a radiolabeled form could image the 
biodistribution at baseline and during therapy in patients receiving the therapeutic drug. The first 
step in the development of such an in vivo marker is to determine the safety of the radiolabeled 
form and the radiation dosimetry.  The resultant pharmacokinetics of [F-18]-FdCyd will 
subsequently be evaluated both with and without non- radiolabeled FdCyd concurrently
administered using PET/CT.  Due to rapid metabolism in the absence of a Cyd/dCyd deaminase 
inhibitor, a trial of single agent [F-18]-FdCyd alone would be irrelevant to the potential clinical 
utility of this drug.  Therefore, the treatment plan of this protocol incorporates a fixed dose of 
THU which is known to be safe, and to effectively diminish the activity of Cyd/dCyd deaminase 
in humans (22).  
3
PATIENT SELECTION 
3.1
Eligibility Criteria
3.1.1
Inclusion Criteria
3.1.1.1
Enrolled in the NIH Phase II Clinical protocol evaluating FdCyd with THU (NCI 
protocol # 09-C-0214 (CTEP# 8351) or NCI protocol #12-C-0066 (CTEP# 9127)) with 
target lesion PHDVXUHGDV 10mm with spiral CT scan.
3.1.1.2
Written, voluntary, informed consent of the patient must be obtained in compliance with 
institutional, state and federal guidelines
3.1.1.3
For females: Negative serum pregnancy test OR post-menopausal for at least 2 years 
OR patient has had a hysterectomy
3.1.2
Exclusion Criteria
3.1.2.1
Participants with severe claustrophobia unresponsive to oral anxiolytics
3.1.2.2
Subjects weighing > 400 lbs (weight limit for scanner table), or unable to fit within the 
imaging gantry
3.1.2.3
Known allergy to FdCyd
3.1.2.4
The subject is unable to lie still for ~75 minutes
3.1.2.5
Pregnant or lactating women. Pregnant women are excluded from this study because the 
effects of 18F-FdCyd in pregnancy are not known. Because there is an unknown but 
potential risk for adverse events in nursing infants secondary to administration of 18F-
FdCyd in the mother, breastfeeding should be discontinued if the mother receives 18F-
FdCyd
3.1.2.6
Participants with any co-existing medical or psychiatric condition that is likely to 
interfere with study procedures and/or results
Page 13 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
3.2
Screening Evaluation
This is a companion study to the therapeutic Phase II 5-FdCyd/THU study (NCI protocol # 09-C-
0214: CTEP # 8351) and Phase I 5-FdCyd/THU study in Patients (NCI protocol # 12-C-0066/ 
CTEP # 9127 open in the NCI Developmental Therapeutics Clinic at the Clinical Center, NIH.  
Both studies are multicenter studies and only patients enrolled at the Clinical Center will be
recruited for this imaging protocol.  After determination of enrollment on NCI protocol # 09-C-
0214(CTEP# 8351) or NCI protocol # 12-C-0066/CTEP# 9127, patients will be approached for 
willingness to participate in this imaging study.  To ensure eligibility for this imaging study, the 
following evaluation will be performed:
3.2.1
History and Physical Examination, including vital signs
3.2.2
Evaluation of Performance Status using the ECOG scale
3.2.3
ȕ+&*RUXULQHSUHJQDQF\WHVW
3.2.4
Review of previous scans to assure measurable disease
3.3
Inclusion of Women and Minorities
Both men and women of all races and ethnic groups are eligible for this trial.  
4
REGISTRATION PROCEDURES
Authorized staff must register an eligible candidate with NCI Central Registration Office (CRO) 
within 24 hours of signing consent.  A registration Eligibility Checklist from the web site 
(http://home.ccr.cancer.gov/intra/eligibility/welcome.htm) must be completed and faxed to 301-
480-0757.  After confirmation of eligibility at Central Registration Office, CRO staff will call 
Molecular Imaging Program (Yolanda McKinney, RN, MIP/CCR/NCI) to advise them of the 
acceptance of the patient on the protocol prior to the release of any investigational agents.  
Verification of Registration will be forwarded electronically via e-mail to the research team.  A 
recorder is available during non-working hours. 
5
STUDY IMPLEMENTATION
5.1
Study Design
Only patients who are enrolled in the therapeutic trials NCI Protocol # 09-C-0214 (CTEP# 8351)
or NCI Protocol # 12-C-0066 (CTEP # 9127) will be recruited for this trial.  The initial [F-18]-
FdCyd + THU PET/CT imaging should be completed prior to therapeutic dosing.  Repeat 
imaging will be performed 2-5 days after the initiation of FdCyd + THU therapy and at least 2 
hours after dosing.
Page 14 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
Patient enrolls in 
parent therapeutic
study (NCI # 09-C-
0214: CTEP# 8351
or NCI# 12-C-0066
:CTEP# 9127)
Patient enrolled in 
this 18FdCyd +THU 
imaging sub-study 
Patient undergoes 
18FdCyd+THU PET/CT 
imaging*
Patient undergoes 2nd 18FdCyd PET/CT 
imaging while receiving a therapeutic dose 
of FdCyd +THU prescribed by the parent
protocol (NCI protocol # 09-C-0214:
CTEP# 8351** or 12-C-0066:CTEP9127
5.2
Study Schema
Figure 4: Imaging session without therapeutic “cold” FdCyd 
Arm 1 (#09-C-0214): 18FdCyd injection 
(between 20-60 min of beginning IV THU)
Arm 2 (#12-C-0066): 18FdCyd injection ( 
approximately 2hrs after oral THU )
Page 15 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
Figure 5:  Imaging session with “cold” FdCyd and administered per NCI protocol # 09-C-
0214 (CTEP# 8351) and NCI protocol #12-C-0066 (CTEP #9127)
5.2.1
Imaging session per NCI protocol #09-C-0214 (CTEP #8351)
For THU administration, an IV bolus of 20% the total dose of tetrahydrouridine (total dose 
of THU = 350 mg/m2) is administered, followed by the other 80% of the dose, diluted in 
250 ml of D5W, which will be infused for 3 hours or until the end of imaging. At least 20
minutes after the tetrahydrouridine IV is begun, the radiopharmaceutical will be 
administered over ~1 minute.  The patient will be imaged continuously from top of head to 
thigh for 60-75 minutes, followed by whole body static imaging at 2 hours post infusion 
(approximately 2.5 hours total). A licensed clinical practitioner will be available during the 
drug administration and imaging session. 
**The 18FdCyd will be administered at least 20 minutes after the THU is begun and 
concurrent with, or following (within 1 hr of) the start of the FdCyd therapeutic dose.
5.2.2
Imaging session per NCI protocol #12-C-0066 (CTEP #9127)
Patients will receive a dose of THU (total dose of THU is 3000 mg ) for the initial scan 
approximately 2 hours (+30 minutes) before injection of the F-18 FdCyd radiotracer. The 
patient will be imaged continuously from top of head to thigh for 60-75 minutes, followed 
by whole body static imaging at 2 hours post radiotracer injection approximately 2.5 hours 
total). A licensed clinical practitioner will be available during the drug administration and 
imaging session.
5.3
Stopping Rules
For the purpose of protecting patient safety, the study will be stopped according to the following 
stopping rule.
Arm 1 (#09-C-0214): 18FdCyd injection 
(between 20-60 min of beginning IV THU)
Arm 2 (#12-C-0066): 18FdCyd injection ( 
approximately 2hrs after oral THU )
Page 16 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
Table 2
Number of Patients
Number of Grade 3 
or 4 CTCAE toxicity
3-6
3
7-12
4
13-18
5
The operating characteristic of the stopping rule was assessed by simulations. Based on 10,000 
simulations, the probability of stopping early for an excess of grade 3 or 4 CTCAE toxicity over 
the course of trial is 4.6% when the toxicity rate is 0.10 and 84% when the toxicity rate is 0.35. 
This is deemed reasonable for protecting patient safety.  
5.4
CTEP IND Agent Administration
5.4.1
5-fluoro-2’-deoxycytidine (FdCyd) and Tetrahydrouridine (THU)
5-fluoro-2’-deoxycytidine (FdCyd) and Tetrahydrouridine (THU) will be administered according 
to the specifications of the parent protocol NCI protocol # 09-C-0214 (CTEP# 8351) or NCI 
Protocol #12-C-0066 (CTEP# 9127).  The investigational agent administered on this study is the 
radiolabeled dose of [F-18]-5-Fluoro-2'-deoxycytidine (FdCyd).
5.4.2
[F-18]-5-Fluoro-2'-deoxycytidine (FdCyd) (NSC #755309)
Intravenous administration:  The imaging dose of [F-18]-FdCyd will be administered to the 
patient ~20 minutes after initiation of the intravenous bolus dose of THU.  It will be 
administered as an IV injection over ~1 minute.
5.4.3
Tetrahydrouridine (THU)
5.4.3.1
Intravenous administration:  
An IV bolus of 20% the total dose of tetrahydrouridine (total dose of THU = 350 mg/m2) is 
administered (over less than 1 minute), followed by the other 80% of the dose, diluted in 250 ml 
of D5W, which will be infused for 3 hours.  
5.4.3.2
Oral Administration:
The dose of THU is fixed at 3000 mg. THU oral solution should be taken on an empty stomach 
at least 1 hour before or 2 hours after a meal, and 30 minutes before taking FdCyd. THU Oral 
Solution should be mixed with 2-3 ounces of an acidic juice to aid in masking the taste (i.e., orange 
juice, apple juice or lemonade) immediately prior to dosing.
5.4.4
PET/CT Imaging
A transmission CT of the imaging field of view (top of head to thigh) will be performed 
immediately prior to radiotracer injection.  Three sequential whole body PET emission scans will 
be performed from top of head to thigh for the first 60-75 minutes.  An additional top of the head 
to thigh scan (~35 minutes) will be acquired at 2 hours post radiotracer injection.  
Page 17 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
Vital signs and queries for potential adverse events will be performed during the imaging at the 
following intervals: 0, 15, 30 minutes, 1-hour and 2-hours post injection. A query for potential 
AEs will also be made 24 +/-8 hrs after (~6 times the t1/2 of the imaging drug) after 
administration.
5.5
General Concomitant Medication and Supportive Care Guidelines
In general, the concomitant medications and supportive care guidelines in the parent protocol 
NCI protocol # 09-C-0214 (CTEP# 8351) or NCI Protocol #12-C-0066 (CTEP# 9127) will be 
followed.  Based on known toxicity, no reactions are expected; however, supportive care may be 
necessary in rare instances when a reaction is encountered.  
Supportive care will be provided for infusion-related reactions such as allergic or anaphylactic 
reactions.  Allergic reactions requiring therapy will be treated according to standard guidelines 
by the attending physician after appropriate medical assessment.  Subjects with significant 
infusion related reactions which are atypical and not successfully treated on site in the Molecular 
Imaging Clinic or which develop later or require closer monitoring may be admitted to the 
inpatient medical oncology service under Dr. Chen for observation/treatment or the ICU as 
needed.
5.6
Duration of Participation
Participants will be taken off this study 1 day after the repeat imaging session is complete.
5.7
Dosing Delays/Dose Modifications
5 mCi of F-18 FdCyd is prescribed. Due to potential unpredictable delays, the total activity
administered may be reduced at the discretion of the PI. A corresponding increase in PET bed 
position acquisition time will be made as needed.
In the unlikely event of complications during the injection (infiltration, adverse reaction), the 
injection will be discontinued.  If the PI determines there are no contraindications, the remaining 
amount of tracer will be injected following resolution of the cause of discontinuation.
5.8
Criteria for Removal from Study
The investigator may withdraw a patient from the study for any of the following reasons:
x
A protocol violation occurs,
x
A serious or intolerable adverse event occurs
x
A clinically significant change in patient status occurs making the patient no longer 
eligible to receive the radiopharmaceutical or undergo the PET/CT imaging 
x
The investigator terminates the study
Authorized staff must notify Central Registration Office (CRO) when a subject is taken off-
study. An off-study form from the web site 
(http://home.ccr.cancer.gov/intra/eligibility/welcome.htm) main page must be completed and 
faxed to 301-480-0757.
6
ADVERSE EVENTS:  LIST AND REPORTING REQUIREMENTS
Page 18 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
Adverse event (AE) monitoring and reporting is a routine part of every clinical trial.  The 
following list of AEs (Section 6.1) and the characteristics of an observed AE (Section 6.2) will 
determine whether the event requires expedited (via CTEP-AERS) in addition to routine
reporting.
6.1
Comprehensive Adverse Events & Potential Risks Lists (CAEPR) for 5-Fluoro-2'-
deoxycytidine (FdCyd, NSC 48006) with Tetrahydrouridine (THU, NSC 112907)
The Comprehensive Adverse Event and Potential Risks list (CAEPR) provides a single list of 
reported and/or potential adverse events (AE) associated with an agent using a uniform 
presentation of events by body system. In addition to the comprehensive list, a subset, the 
Specific Protocol Exceptions to Expedited Reporting (SPEER), appears in a separate column and 
is identified with bold and italicized text. This subset of AEs (SPEER) is a list of events that are 
protocol specific exceptions to expedited reporting to NCI (except as noted below).  Refer to the 
'CTEP, NCI Guidelines: Adverse Event Reporting 
Requirements' http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/aeguidel
ines.pdf for further clarification. Frequency is provided based on 166 patients. Below is the 
CAEPR for 5-Fluoro-2'-deoxycytidine with tetrahydrouridine (FdCyd/THU).
NOTE: Report AEs on the SPEER ONLY IF they exceed the grade noted in parentheses next to 
the AE in the SPEER.  If this CAEPR is part of a combination protocol using multiple 
investigational agents and has an AE listed on different SPEERs, use the lower of the grades to 
determine if expedited reporting is required..
Version 2.2, January 17, 20141
Adverse Events with Possible 
Relationship to 5-Fluoro-2'-deoxycytidine with tetrahydrouridine 
(FdCyd/THU)
(CTCAE 4.0 Term)
[n= 166]
Specific Protocol Exceptions to Expedited 
Reporting (SPEER) 
Likely (>20%)
Less Likely (<=20%)
Rare but Serious (<3%)
BLOOD AND LYMPHATIC SYSTEM DISORDERS
Anemia
Anemia (Gr 2)
Febrile neutropenia
CARDIAC DISORDERS
Sinus tachycardia
Sinus tachycardia (Gr 2)
GASTROINTESTINAL DISORDERS
Abdominal distension
Abdominal pain
Abdominal pain (Gr 2)
Constipation
Constipation (Gr 2)
Diarrhea
Diarrhea (Gr 2)
Dry mouth
Dyspepsia
Flatulence
Ileus
Mucositis oral
Mucositis oral (Gr 2)
Nausea
Nausea (Gr 2)
Vomiting
Vomiting (Gr 2)
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS
Chills
Chills (Gr 2)
Page 19 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
Edema limbs
Fatigue
Fatigue (Gr 2)
Fever
Fever (Gr 2)
Non-cardiac chest pain
Pain
INVESTIGATIONS
Activated partial 
thromboplastin time 
prolonged
Activated partial thromboplastin time prolonged 
(Gr 2)
Alanine aminotransferase 
increased
Alanine aminotransferase increased (Gr 2)
Alkaline phosphatase 
increased
Alkaline phosphatase increased (Gr 2)
Aspartate aminotransferase 
increased
Aspartate aminotransferase increased (Gr 2)
Blood bilirubin increased
Blood bilirubin increased (Gr 2)
Cholesterol high
Creatinine increased
Creatinine increased (Gr 2)
Lymphocyte count decreased
Lymphocyte count decreased (Gr 2)
Neutrophil count decreased
Neutrophil count decreased (Gr 2)
Platelet count decreased
Platelet count decreased (Gr 2)
Weight loss
Weight loss (Gr 2)
White blood cell decreased
White blood cell decreased (Gr 2)
METABOLISM AND NUTRITION DISORDERS
Anorexia
Anorexia (Gr 2)
Dehydration
Dehydration (Gr 2)
Hypercalcemia
Hyperglycemia
Hyperglycemia (Gr 2)
Hyperkalemia
Hypermagnesemia
Hypoalbuminemia
Hypoalbuminemia (Gr 2)
Hypocalcemia
Hypocalcemia (Gr 2)
Hypokalemia
Hypokalemia (Gr 2)
Hypomagnesemia
Hypomagnesemia (Gr 2)
Hyponatremia
Hyponatremia (Gr 2)
Hypophosphatemia
Hypophosphatemia (Gr 2)
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS
Arthralgia
Generalized muscle 
weakness
Myalgia
NERVOUS SYSTEM DISORDERS
Dizziness
Dizziness (Gr 2)
Dysgeusia
Headache
Headache (Gr 2)
Peripheral motor 
neuropathy
Peripheral motor neuropathy (Gr 2)
Peripheral sensory 
neuropathy
RENAL AND URINARY DISORDERS
Proteinuria
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS
Cough
Dyspnea
Dyspnea (Gr 2)
Epistaxis
Page 20 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
SKIN AND SUBCUTANEOUS TISSUE DISORDERS
Alopecia
Dry skin
Hyperhidrosis
Palmar-plantar 
erythrodysesthesia 
syndrome
Pruritus
Rash maculo-papular
VASCULAR DISORDERS
Hypotension
Hypotension (Gr 2)
1This table will be updated as the toxicity profile of the agent is revised.  Updates will be distributed to all 
Principal Investigators at the time of revision.  The current version can be obtained by 
contacting PIO@CTEP.NCI.NIH.GOV. Your name, the name of the investigator, the protocol and the 
agent should be included in the e-mail.
Also reported on FdCyd/THU trials but with the relationship to FdCyd/THU still undetermined:
CARDIAC DISORDERS - Aortic valve disease; Atrial fibrillation; Cardiac arrest; Mitral valve disease; 
Myocardial infarction; Palpitations; Pericardial effusion; Pericarditis; Tricuspid valve disease; Ventricular 
tachycardia
EAR AND LABYRINTH DISORDERS - Ear pain; Middle ear inflammation; Tinnitus
EYE DISORDERS - Blurred vision; Conjunctivitis; Dry eye; Eye disorders - Other (right eye blindness [90-95% 
visual acuity loss]); Eye disorders - Other (subconjuctival hemorrhage); Eye disorders - Other (visual changes); Eye 
pain; Floaters; Photophobia; Watering eyes
GASTROINTESTINAL DISORDERS - Bloating; Colitis; Colonic obstruction; Duodenal ulcer; Dysphagia; 
Esophagitis; Gastrointestinal disorders - Other (pyloric ulcer); Gastrointestinal pain; Hemorrhoids; Lip pain; Oral 
pain; Rectal hemorrhage; Typhlitis; Upper gastrointestinal hemorrhage
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - Edema face; Flu like symptoms; 
Infusion site extravasation; Injection site reaction; Localized edema; Malaise
INFECTIONS AND INFESTATIONS - Enterocolitis infectious; Eye infection; Lung infection; Mucosal 
infection; Sepsis; Skin infection; Upper respiratory infection
INJURY, POISONING AND PROCEDURAL COMPLICATIONS - Bruising; Vascular access complication
INVESTIGATIONS - CPK increased; Hemoglobin increased; INR increased; Investigations - Other (bicarbonate)
METABOLISM AND NUTRITION DISORDERS - Alkalosis; Hypernatremia; Hypertriglyceridemia; 
Hyperuricemia; Hypoglycemia
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS - Arthritis; Back pain; Bone pain; Chest 
wall pain; Joint range of motion decreased; Neck pain; Pain in extremity
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS) - Tumor pain
NERVOUS SYSTEM DISORDERS - Cognitive disturbance; Nervous system disorders - Other (neuropathy -
cranial); Neuralgia; Syncope; Tremor
PSYCHIATRIC DISORDERS - Agitation; Anxiety; Confusion; Depression; Insomnia
RENAL AND URINARY DISORDERS - Cystitis noninfective; Hematuria; Hemoglobinuria; Renal and urinary 
disorders - Other (bladder pain); Renal and urinary disorders - Other (urethra pain); Urinary frequency; Urinary 
incontinence; Urinary tract pain
Page 21 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
REPRODUCTIVE SYSTEM AND BREAST DISORDERS - Breast pain; Gynecomastia; Pelvic pain
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - Allergic rhinitis; Bronchopulmonary 
hemorrhage; Hiccups; Hypoxia; Pleural effusion; Sore throat
SKIN AND SUBCUTANEOUS TISSUE DISORDERS - Bullous dermatitis; Nail discoloration; Periorbital 
edema; Purpura; Rash acneiform; Skin and subcutaneous tissue disorders - Other (folliculitis); Skin 
hyperpigmentation; Skin hypopigmentation; Skin ulceration
VASCULAR DISORDERS - Flushing; Hot flashes; Hypertension
Note: FdCyd/THU in combination with other agents could cause an exacerbation of any adverse event currently 
known to be caused by the other agent, or the combination may result in events never previously associated with 
either agent.
6.1.1
Adverse Events and Potential Risks of [F-18] FdCyd
This is a first in human study of the radioactive form of FdCyd. [F-18]-FdCyd administration at 
the chemical dose described for this study is low 30mg). Patients on this study will be 
monitored for adverse events for 10 half-lives (1 day).
No adverse effects are expected as a result of the administration of [F-18]-FdCyd. Potential 
adverse effects from the tracer injection are listed below:
x
Infection at the injection site or systemic infection
x
Extravasation of the dose
x
Allergic reaction
x Vasovagal reaction
6.1.2
Adverse Events and Potential Risks for THU
THU has no expected side effects at the dose used in this study, but THU may increase the risk 
of experiencing FdCyd side effects.
6.2
Adverse Event Characteristics 
x
CTCAE term (AE description) and grade:  The descriptions and grading scales 
found in the revised NCI Common Terminology Criteria for Adverse Events 
(CTCAE) version 4.0 will be utilized for AE reporting.  All appropriate treatment 
areas should have access to a copy of the CTCAE version 4.0.  A copy of the CTCAE 
version 4.0 can be downloaded from the CTEP web 
site http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm.
x
‘Expectedness’: AEs can be ‘Unexpected’ or ‘Expected’ (see Section 6.1 above) for 
expedited reporting purposes only.  ‘Expected’ AEs (the ASAEL) are bold and 
italicized in the CAEPR (Section 6.1.1).
x
Attribution of the AE:

Definite – The AE is clearly related to the study treatment.

Probable – The AE is likely related to the study treatment.

Possible – The AE may be related to the study treatment.

Unlikely – The AE is doubtfully related to the study treatment.

Unrelated – The AE is clearly NOT related to the study treatment.
Page 22 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
6.2.1
Suspected adverse reaction
Suspected adverse reaction means any adverse event for which there is a reasonable possibility 
that the drug caused the adverse event. For the purposes of IND safety reporting, ‘reasonable 
possibility’ means there is evidence to suggest a causal relationship between the drug and the 
adverse event. A suspected adverse reaction implies a lesser degree of certainty about causality 
than adverse reaction, which means any adverse event caused by a drug.
6.2.2
Unexpected adverse reaction
An adverse event or suspected adverse reaction is considered “unexpected” if it is not listed in 
the investigator brochure or is not listed at the specificity or severity that has been observed; or, 
if an investigator brochure is not required or available, is not consistent with the risk information 
described in the general investigational plan or elsewhere in the current application. 
"Unexpected”, also refers to adverse events or suspected adverse reactions that are mentioned in 
the investigator brochure as occurring with a class of drugs or as anticipated from the 
pharmacological properties of the drug, but are not specifically mentioned as occurring with the 
particular drug under investigation.
6.2.3
Serious 
An Unanticipated Problem or Protocol Deviation is serious if it meets the definition of a Serious 
Adverse Event or if it compromises the safety, welfare or rights of subjects or others.
6.2.4
Serious Adverse Event
An adverse event or suspected adverse reaction is considered serious if in the view of the 
investigator or the sponsor, it results in any of the following:
x
Death, 
x
A life-threatening adverse drug experience 
x
Inpatient hospitalization or prolongation of existing hospitalization 
x
Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
x
A congenital anomaly/birth defect 
x
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse drug experience when, based upon 
appropriate medical judgment, they may jeopardize the patient or subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in this definition. 
6.2.5
Disability
A substantial disruption of a person’s ability to conduct normal life functions.
6.2.6
Life-threatening adverse drug experience
Any adverse event or suspected adverse reaction that places the patient or subject, in the view of 
the investigator or sponsor, at immediate risk of death from the reaction as it occurred, i.e., it 
does not include a reaction that had it occurred in a more severe form, might have caused death.
Page 23 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
6.2.7
Protocol Deviation (NIH Definition): 
Any change, divergence, or departure from the IRB approved study procedures in a research 
protocol that does not have a major impact on the subject’s rights, safety or well-being, or the 
completeness, accuracy and reliability of the study data.-approved research protocol.
6.2.8
Non-compliance (NIH Definition)
The failure to comply with applicable NIH Human Research Protections Program (HRPP) 
policies, IRB requirements, or regulatory requirements for the protection of human research 
subjects.
6.2.9
Unanticipated Problem
Any incident, experience, or outcome that:
x
Is unexpected in terms of nature, severity, or frequency in relation to 
(a) the research risks that are described in the IRB-approved research protocol and 
informed consent document; Investigator’s Brochure or other study documents, and
(b) the characteristics of the subject population being studied; AND
x
Is related or possibly related to participation in the research; AND
x
Suggests that the research places subjects or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized.
6.3
Expedited Adverse Event Reporting
6.3.1
Expedited AE reporting for this study must use CTEP-AERS (CTEP Adverse Event 
Reporting System), accessed via the CTEP home page (http://ctep.cancer.gov).  The 
reporting procedures to be followed are presented in the “CTEP, NCI Guidelines: 
Adverse Event Reporting Requirements” which can be downloaded from the CTEP home 
page (http://ctep.cancer.gov).  These requirements are briefly outlined in the table below 
(Section 6.3.3).
6.3.2
In the rare event when Internet connectivity is disrupted a 24-hour notification is to be 
made to NCI by telephone at: 301-897-7497, or 301-897-7402 for CIP studies. An 
electronic report MUST be submitted immediately upon re-establishment of internet 
connection. Please note that all paper CTEP-AERS forms have been removed from the 
CTEP website and will NO LONGER be accepted.
6.3.3
Expedited Reporting Requirements for Adverse Events that Occur on Studies under an 
IND/IDE within 30 Days of the Last Administration of the Investigational 
Agent/Intervention1, 2
Page 24 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
Table 3
FDA REPORTING REQUIREMENTS FOR SERIOUS ADVERSE EVENTS (21 CFR 
Part 312)
NOTE: Investigators MUST immediately report to the sponsor (NCI) ANY Serious Adverse 
Events, whether or not they are considered related to the investigational 
agent(s)/intervention (21 CFR 312.64)
An adverse event is considered serious if it results in ANY of the following outcomes:  
1) Death
2) A life-threatening adverse event 
3) An adverse event results in inpatient hospitalization or prolongation of existing 
KRVSLWDOL]DWLRQIRUKRXUV
4) A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
5) A congenital anomaly/birth defect. 
6)
Important Medical Events (IME) that may not result in death, be life threatening, or 
require hospitalization may be considered serious when, based upon medical judgment, 
they may jeopardize the patient or subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition (FDA, 21 CFR 
312.32; ICH E2A and ICH E6).
ALL SERIOUS adverse events that meet the above criteria MUST be immediately reported 
to the NCI via CTEP-AERS within the timeframes detailed in the table below.
Grade 1 and 2 Timeframes
Grade 3-5 Timeframes.
10 Calendar Days
24-Hour 5 Calendar Days
Expedited AE reporting timelines are defined as:
o
“24-Hour; 5 Calendar Days” - The AE must initially be reported via CTEP-
AERS within 24 hours of learning of the AE, followed by a complete expedited 
report within 5 calendar days of the initial 24-hour report.
o
“10 Calendar Days” - A complete expedited report on the AE must be 
submitted within 10 calendar days of learning of the AE.
1Serious adverse events that occur more than 30 days after the last administration of 
investigational agent/intervention require reporting as follows:
Expedited 24-hour notification followed by complete report within 5 calendar days for ALL
Grade 4 and 5 AEs and Grade 3 AEs with at least a possible attribution.
2For studies using PET or SPECT IND agents, the AE reporting period is limited to 10 
radioactive half-lives, rounded UP to the nearest whole day, after the agent/intervention 
was last administered.  Footnote “1” above applies after this reporting period.
Effective Date:  May 5, 2011
Page 25 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
6.4
Protocol-Specific Expedited Adverse Event Reporting Exclusions
For this protocol only, AEs/grades that occur as a result of the therapy or participation in the 
parent protocol (NCI protocol # 09-C-0214: (CTEP# 8351) or NCI Protocol #12-C-0066: 
(CTEP# 9127)) are exceptions to the Expedited Reporting Guidelines and do not require 
expedited reporting (i.e., CTEP-AERS).  These AEs will be reported according to the expedited 
or routine reporting guidelines in NCI protocol # 09-C-0214 (CTEP# 8351) or NCI Protocol #12-
C-0066 (CTEP# 9127).
6.5
Routine Adverse Event Reporting
All Adverse Events must be reported in routine study data submissions.  AEs reported through 
CTEP-AERS must also be reported in routine study data submissions. All AEs will be 
reported through CDUS.
6.6
Secondary AML/MDS
AML/MDS events must be reported via CTEP-AERS (in addition to your routine AE reporting 
mechanisms). In CTCAE v4.0, the event(s) may be reported as either: 1) Leukemia secondary to 
oncology chemotherapy, 2) Myelodysplastic syndrome, or 3) Treatment-related secondary 
malignancy.
6.7
NCI-IRB Reporting
6.7.1
NCI-IRB Expedited Reporting of Unanticipated Problems, and Deaths
The Protocol PI will report to the NCI-IRB:
x
All deaths, except deaths due to progressive disease
x
All Protocol Deviations
x
All Unanticipated Problems
x
All serious non-compliance
Reports must be received by the NCI-IRB within 7 working days of PI awareness via iRIS.
6.7.2
NCI-IRB Requirements for PI Reporting at Continuing Review
The protocol PI will report to the NCI-IRB: 
1.
A summary of all protocol deviations in a tabular format to include the date the 
deviation occurred, a brief description of the deviation and any corrective action. 
2.
A summary of any instances of non-compliance 
3.
A tabular summary of the following adverse events: 
x
All Grade 2 unexpected events that are possibly, probably or definitely related to the 
research;  
x
All Grade 3 and 4 events that are possibly, probably or definitely related to the 
research;  
x
All Grade 5 events regardless of attribution;  
x
All Serious Events regardless of attribution.  
Page 26 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
NOTE: Grade 1 events are not required to be reported. 
6.7.3
NCI-IRB Reporting of IND Safety Reports
Only IND Safety Reports that require a sponsor recommended change to meet the protocol or the 
consent form or in the opinion definition of the PI increases risks to study participants an
unanticipated problem will need to be reported to the NCI IRB.
7
PHARMACEUTICAL INFORMATION
7.1
[F-18]-5-Fluoro-2'-deoxycytidine (FdCyd) NSC# 755309
7.1.1
Molecular Formula:
C9H12
18FN3O4
7.1.2
Molecular Weight:
244.2
7.1.3
How Supplied:
5-fluoro-2’-deoxycytidine is supplied as a sterile, single use vial.  [F-18]-5-Fluoro-2'-
deoxycytidine (FdCyd) Injection is formulated in sterile saline and is manufactured by the 
University of Pennsylvania, Philadelphia, PA.  It is prepared for each patient on the day of 
administration and shipped to the address below:
Division of Radiation Safety
National Institutes of Health
Building 21 Room 107
21 Wilson Drive
Bethesda, MD 20892-6780
The dose is 5 mCi or less at the time of administration, a mass dose of <30mg
7.1.4
Storage:
Intact vials should be stored at controlled room temperature. An expiration time will be listed on 
vial label
7.1.5
Route of Administration:
Intravenous
7.1.6
Preparation:
The agent is manufactured according to the University of Pennsylvania Standard Operating 
Procedures.
7.1.7
Method of Administration:
FdCyd may be mixed tetrahydrouridine (THU NSC 112907) in D5W and is stable for at least 24 
hours at room temperature. See Section 5.4.2 for details about [F-18]-FdCyd administration.
Page 27 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
7.1.8
Availability
[F-18]-5-Fluoro-2'-deoxycytidine (FdCyd) Injection is an investigational agent supplied to 
investigators by the University of Pennsylvania.
7.1.9
Agent Ordering
NCI-supplied agents may be requested by the Principal Investigator (or their authorized 
designee) at each participating institution
18F FdCyd will be ordered directly from the University of Pennsylvania.
7.1.10 Agent Accountability
Agent Inventory Records – The investigator, or a responsible party designated by the 
investigator, must maintain a careful record of the inventory and disposition of all agents 
received from DCTD using the NCI Drug Accountability Record Form (DARF).  (See the CTEP 
home page at http://ctep.cancer.gov for the Procedures for Drug Accountability and Storage and 
to obtain a copy of the DARF and Clinical Drug Request form.)
7.2
Tetrahydrouridine (THU) (NSC 112907)
7.2.1
Tetrahydrouridine (THU) Injection 
Chemical Name: 2(1H)-pyrimidinone, tetrahydro-4-hydroxy-1.beta.-D-ribofuranosyl-
Other Names:
THU, H4U
CAS Registry Number:  18771-50-1
Molecular Formula: C9H16N2O6
M.W.:  248
Approximate Solubility:  The drug is highly soluble in water up to 200 mg/mL at pH 7.0.
Mode of Action:  Cytidine deaminase inhibitor
How Supplied:
Tetrahydrouridine Injection is supplied by the DCTD and distributed by 
the PMB/NCI as a 500 mg vial (10 mg/mL; 50 mL).  The clear, colorless solution contains 10 
mg tetrahydrouridine per mL with dibasic phosphate, USP, monobasic phosphate, USP used as 
buffer to maintain pH at 7.4.
Preparation: Tetrahydrouridine may be administered without further dilution or may be further 
diluted in 0.9% Sodium Chloride Injection, USP or 5% dextrose injection, USP to a 
concentration as low as 2.5 mg/mL.
Storage:
Intact vials should be stored in the refrigerator (2o – 8oC).
Stability:
Shelf life stability testing of the intact vials is on-going.  Tetrahydrouridine as 
diluted above is stable for at least 24 hours at room temperature.
CAUTION:  The single-use vial contains no antibacterial preservatives.  Therefore, it is advised 
that the product be discarded 8 hours after initial entry. 
Route of Administration:  Intravenous for subjects enrolled from NCI Protocol 09-C-0214
(CTEP# 8351)
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7.2.2
Tetrahydrouridine Powder for Oral Solution (NSC 112907)
Chemical Name: 2(1H)-pyrimidinone, tetrahydro-4-hydroxy-1.beta.-D-ribofuranosyl-
Other Names:  THU, H4U
CAS Registry Number: 18771-50-1
Molecular Formula:  C9H16N2O6
M.W.:
248
Approximate Solubility:  The drug is highly soluble in water, up to 200 mg/mL.
Mode of Action:  Cytidine deaminase inhibitor
How Supplied:
Tetrahydrouridine is supplied by the DCTD and distributed by the 
PMB/NCI in a single-use amber plastic bottle, with a tamper-evident cellophane seal around the 
bottle neck, containing 3 grams of Tetrahydrouridine Powder for Oral Solution. 
Preparation for Oral Administration:
Reconstitute each 3 gram bottle with 30 mL water 
(distilled or tap water may be used).  Swirl to dissolve powder. 
Storage:
Store intact bottles and reconstituted solution in the refrigerator (2-8oC).  
Stability:
Shelf life stability testing of the intact bottles is on-going.  Reconstituted solutions 
are stable in the amber plastic bottle for up to 3 weeks at refrigerated temperature.
Route of Administration:
Oral for subjects enrolled from NCI Protocol 12-C-0066 (CTEP# 
9127)
Method of Administration: THU oral solution should be taken on an empty stomach at least 1 
hour before or 2 hours after a meal, and 30 minutes before FdCyd dosing. Immediately prior to 
dosing, patients should mix the reconstituted THU oral solution with 2-3 ounces of an acidic 
juice to aid in masking the taste (i.e., orange juice, apple juice or lemonade).
7.2.3
Agent Ordering
NCI-supplied agents may be requested by the Principal Investigator (or their authorized 
designee) at each participating institution. Pharmaceutical Management Branch (PMB) policy 
requires that agent be shipped directly to the institution where the patient is to be treated. PMB 
does not permit the transfer of agents between institutions (unless prior approval from PMB is 
obtained). The CTEP-assigned protocol number must be used for ordering all CTEP-supplied 
investigational agents. The responsible investigator at each participating institution must be 
registered with CTEP, DCTD through an annual submission of FDA Form 1572 (Statement of 
Investigator), Curriculum Vitae, Supplemental Investigator Data Form (IDF), and Financial 
Disclosure Form (FDF). If there are several participating investigators at one institution, CTEP-
supplied investigational agents for the study should be ordered under the name of one lead 
investigator at that institution. 
Active CTEP-registered investigators and investigator-designated shipping designees and 
ordering designees can submit agent requests through the PMB Online Agent Order Processing 
(OAOP) application (https://eapps-ctep.nci.nih.gov/OAOP/pages/login.jspx). Access to OAOP 
requires the establishment of a CTEP Identity and Access Management (IAM) account 
(https://eapps-ctep.nci.nih.gov/iam/) and the maintenance of an “active” account status and a 
“current” password. For questions about drug orders, transfers, returns, or accountability, call 
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Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
(240) 276-6575 Monday through Friday between 8:30 am and 4:30 pm (ET) or email 
PMBAfterHours@mail.nih.gov anytime.
7.2.4
Agent Accountability
The Principal Investigator or a responsible party designate by the PI will retain a careful record 
of the inventory and disposition of all agents received from DCTD using the NCI Drug 
Accountability Record Form per CTEP Policy and Guidelines for Accountability and Storage of 
Investigational Drugs (http://ctep.cancer.gov/protocolDevelopment/default.htm#agents_drugs).
Page 30 of 39


Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
8
STUDY CALENDAR
Patients on the IV FdCyd + THU protocol (NCI Protocol# 09-C-0214: CTEP#8351) will receive
THU at least 20 minutes prior to and through the imaging. On their on-therapy scan (repeat 
imaging session), they will additionally receive cold FdCyd as prescribed by the referring 
protocol.
Patients on the oral FdCyd + THU protocol (NCI Protocol 12-C-0066: CTEP#9127) will receive
THU approximately 2 hrs (+30 minutes) prior to the imaging.  On their on-therapy scan (repeat 
imaging session), the patients will receive their therapeutic FdCyd + THU approximately 2 hrs 
(+30 minutes) prior to the imaging.
PET/CT Imaging Sessions
Baseline
Evaluation
Day of 
imaging
0h
+2.0h
+1
day
18F-5-Fluoro-2'-
DeoxycytidineA (18FdCyd)
X
Informed consent
X
Demographics
X
Medical history
X
Physical exam
X
Record Concurrent Meds
X
X
X
Performance status
X
ȕ+&*RUXULQHSUHJQDQF\
test
X
Adverse Event evaluation
X
X
X
X
Vital Signs
X
3 Dynamic regional Serial 
whole body PET/CT 
ImagingB
X
Static Repeat whole body 
PET/CT Imaging
X
A. CTEP IND Agent:  ~5mCi 18F-5-Fluoro-2'-Deoxycytidine single intravenous injection
B. PET/CT imaging sessions will be performed pre-cycle under the Phase II FdCyd + THU protocol (NCI
Protocol # 09-C-0214: CTEP# 8351 or Phase I FdCyd + THU protocol (NCI # 12-C-0066: CTEP 9127)and while 
receiving FdCyd +THU as prescribed by the protocol (2-5 days after cycle initiation)
9
MEASUREMENT OF EFFECT: IMAGE ANALYSIS
9.1
Tumor evaluation
x
The location of the target lesion will be identified on the transmission CT
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Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
x
18FdCyd uptake greater than or equal to 20% of the surrounding background (tumor to 
background ratio >=1.2) will be considered to be qualitatively “positive” 
x
All regions/volumes of interest will be saved. Region volumes, and SUV values will be 
output to an Excel spreadsheet using MIM imaging software (www.mimsoftware.com)
x
For lesions with uptake greater than background, an estimated smoothed maximum 
SUV (SUVmax) will be reported as the mean SUV value of an automated 80% 
maximum pixel value threshold based volume of interest (i.e. the average SUV of the 
“hottest” 20% of pixels in the user defined lesion).  This method reduces the chances of 
the SUVmax value being dominated by one or more “noisy” pixel values.
x
Volumetric ROIs will also be constructed based on manual tumor edge detection on 
transmission CT and a 50% SUV based threshold and the MIM Vista “PET edge” tool.  
These volumes will be used to estimate the total tumor tracer uptake and average 
uptake/gram of tissue.
A small VOI will be defined within the left ventricular cavity (LV), left atrium (LA) or largest 
vessel in the field of view. This will be used to obtain an image-derived input function. 
Graphical analyses will be performed using the organ/tumor TAC and the image derived input 
function and 
x
Decay corrected time activity curves will be generated.  
Analysis of the uptake will be dependent on whether a “reversible” or “irreversible” 
tracer uptake pattern is found.  In addition to SUV values at discrete time points, either 
Logan or Patlak graphical analysis will be performed (corrected for metabolites if 
necessary), using an image based input functions. Kinetic analysis may also be 
performed if indicated.
9.2
Dosimetry Estimates
9.2.1
Solid Organs and Tumors
Regions of interest will be drawn within a homogeneous region within the organ of interest 
(identified on transmission CT if necessary).  Anon decay corrected time activity curve (TAC) 
will be obtained from the serial whole body images 
9.2.2
Hollow Organs
Regions encompassing the entire organ (i.e. gall bladder, intestine, bladder) will be initially 
drawn on CT and transposed onto the PET images. The final VOI’s may be adjusted for 
“spillout” based on the PET images. Total activity within the VOIs will be computed for each 
organ at each time point.
Residence times will be calculated from the time activity curves and dosimetry estimates will be 
calculated using OLINDA software.
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Abbreviated Title: [F-18] FdCyd Imaging
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Protocol Number: CTEP 8865, NCI 12-C-0014
10
DATA REPORTING / REGULATORY CONSIDERATIONS 
10.1 Data Collection
Data will be collected by the Molecular Imaging Program research nurse in a password-protected 
file in NCI C3D.  The data will be entered at least on a weekly basis. 
Data collection will include demographics, the site and size of the primary tumor, diagnosis date, 
biopsy date, and pathological diagnosis including tumor grade.  Pharmacokinetic data will be 
generated and stored in a secure database.  Raw image data will be stored on a secure external 
drive.  Reconstructed imaging data will include storage of anonymized images from each time 
point and other extracted image parameters.  This will be stored in a secure, password protected 
imaging database.  Dosimetry (relative organ count rates and per cent injected dose estimates to 
the major organs) results will be calculated using OLINDA (Vanderbilt University, Nashville, 
Tennessee).
10.2 Data Monitoring
This study will be monitored by the Clinical Data Update System (CDUS) Version 3.0.Data will 
be entered electronically on C3D and appropriate reports generated for periodic review.
Clinical Data: The investigators will provide quarterly reports of clinical data on the C3D clinical 
trial software. Cumulative C3D will be submitted quarterly to CTEP by electronic means. 
Reports are due January 31, April 30, July 31, and October 31.
Imaging Data: DICOM datasets (or digital datasets for non-DICOM studies) - of the PET, PET-
CT and pertinent anatomic studies the patients undergo on the trial will be submitted quarterly to 
CTEP via the NCIA (NCI Imaging Archive). The electronic transfer of image datasets is due 
January 31, April 30, July 31, and October 31.
10.3 Sample Storage, Tracking and Disposition
Blood samples will be collected for screening and on-study clinical laboratory safety 
assessments.  All blood samples will be processed and handled in accordance with standard 
laboratory procedures.  All samples will be analyzed at the NCI Clinical Center laboratory.
11 STATISTICAL SECTION  
The purpose of the study is to determine the safety of [F-18]-5-fluoro-2’-deoxycytidine (FdCyd) 
administered intravenously with administration of tetrahydrouridine (THU).  As such, the sample 
size is targeted at 18 evaluable patients, which is adequate to assess the toxicity rate.  With 18 
evaluable patients, the width of the 80% expected confidence interval of 10% and 20% toxicity 
rate is 0.18 and 0.24, respectively.  
To account for the possibility of a small number of inevaluable patients, the accrual ceiling is set 
at 20 patients.
Accruing approximately 1 patient/ month, this protocol is expected to be completed within 1.5 
years.
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Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
12 HUMAN SUBJECTS PROTECTIONS 
12.1 Rationale For Subject Selection
12.1.1 Participants participating in the parent Phase II FdCyd IV therapy study (NCI protocol # 
09-C-0214: CTEP# 8351) or the Phase I FdCyd Oral therapy study NCI Protocol #12-C-
0066 (CTEP# 9127) will be invited to participate prior to beginning treatment under that 
protocol.
12.1.2 All ethnicities and races are eligible for participation  
12.1.3 Participants older than 18 are included  
12.2 Participation of Children
The effects of [F-18]-FdCyd have not been studied in children, and children are more sensitive to 
radiation exposure than adults.  Thus, we will not include children in this study.
12.3 Evaluation of Benefits and Risks/Discomforts
There is no possibility of direct benefit to participants in this Phase 0 study.  The results of this 
trial could generate generalizable information that may benefit future patients with cancer and 
therefore, subjects may benefit by knowing they have contributed to scientific knowledge.  
The risks for participating are also small.  Non-radiolabeled FdCyd has been administered to 
patients at higher doses under the parent study, and at this lower chemical dose (< 5mg) no 
FdCyd related adverse events are expected.  No adverse effects are expected from 
tetrahydrouridine infusion.
Specific risks and potential complications will be clearly outlined in a separate consent form at 
the time of each procedure.  Most complications are expected to be minor and require no 
treatment.  Risks and discomforts associated with [F-18]-FdCyd PET/CT imaging are discomfort 
of an IV placement and the theoretical effects of additional radiation exposure (ED estimated at 
3.52 rem).  The subject will be required to lay still on their back for ~60 minutes for the longest 
scan. 
A licensed clinical practitioner will be immediately available during the injection and imaging 
period and they will be backed by the Clinical Center’s Code team.  If hospitalization is required 
the participant will be admitted.  However, this is unlikely to occur based on what is known of 
these agents.  There is an added inconvenience of having to return for a follow-up scan that the 
subjects will be made aware of.  
Adverse events will be reviewed after every case and a decision will be made about moving 
forward to the next participant so that each participant will have the benefit of the prior 
participant’s experience.
As this is a new imaging test, the alternative is to choose not to participate.
12.4 Consent and Assent Process and Documentation
The participant will be informed of the study by a member of Dr Chen's team and the subject 
will contact the study research nurse who will explain the study in detail and send the consent 
form and protocol (if requested) to the participant.  If the participant has any questions they will 
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Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
be answered by telephone.  A signed consent will be obtained by the principal investigator or an 
associate investigator on the day of the study.  The original signed consent goes to Medical 
Records; a copy is placed in the research record.
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Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
13 REFERENCES 
1.
Carter, S.K. (1976) Large-bowel cancer - the current status of treatment.  J Natl Cancer 
Inst  56:3-10.
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Doroshow, J.H., Multhauf, P., Leong, L., Margolin, K., Litchfield, T., Akman, S., Carr, 
B., Bertrand, M., Goldberg, D., Blayney, D., Odujinrin, O., DeLap, R., Shuster, J., and 
Newman, E. (1990) Prospective randomized comparison of fluorouracil versus 
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advanced measurable colorectal cancer in patients previously unexposed to 
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Hartmann, J.R., Origenes, M.L., Murphy, M.L., Sitarz, A., and Erlandson, M. (1964) 
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childhood leukemia.  Cancer Chemother Rep 34:51-54.
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Keyomarsi, K., and Moran, R.G. (1986) Folinic acid augmentation of the effects of 
fluoropyrimidines on murine and human leukemic cells.  Cancer Res 46:5229-5235.
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Heidelberger, C.  Fluorinated pyrimidines and their nucleosides.  In: Sartorelli, A.C. and 
Johns, D.G. (eds) Handbook of experimental pharmacology antineoplastic and 
immunosuppressive agents. Berlin, Springer Verlag, 1975 pp 193-231.
6.
Ensminger, W.D., Rosowsky, A., Raso, V., Levin, D.C., Glode, M., Come, S., Steele, G., 
and Frei, E., III. (1978) A clinical-pharmacological evaluation of hepatic arterial 
infusions of 5-fluoro-2'deoxyuridine and 5-fluorouracil. Cancer Res 38:3784-3792.
7.
Buroker, T.R., Moertel, C.G., Fleming, T.R., Everson, L.K., Cullinan, S.A., Krook,  J.E., 
Mailliard, J.A., Marschke, R.F., Klaassen, D.J., Laurie, J.A., and Moon, M.D. (1985) A 
controlled evaluation of recent approaches to biochemical modulation or enhancement of 
5-fluorouracil therapy in colorectal carcinoma.  J Clin Oncol 3:1624-1631.
8.
Windschitl, H.E., O'Connell, M.J., Wieand, H.S., Krook, J.E., Rubin, J., Moertel, C.G., 
Kugler, J.W., Pfeifle, D.M., Goldberg, R.M., and Laurie, J.A. (1990) A clinical trial of 
biochemical modulation of 5-fluorouracil with N-phosphonoacetyl-L-aspartate and 
thymidine in advanced gastric and anaplastic colorectal cancer. Cancer 66:853-856.
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Pogolotti, A.L., Nolan, P.A., and Santi, D.V.(1981) Methods for the complete analysis of 
5fluorouracil metabolites in cell extracts.  Anal Biochem 117:178-186.
10.
Friedkin, M. and Roberts, D. (1954) The enzymatic synthesis of nucleosides. II. 
Thymidine and related pyrimidine nucleosides.  J Biol Chem 207:257-266.
11.
De Verdier, C-H and Potter, V.R. (1960) Alternative pathways of thymine and uracil 
metabolism in the liver and hepatoma.  J Natl Cancer Inst 24:13-29.
12.
Newman, E.M. and Santi, D.V. (1982) Metabolism and mechanism of action of 5-
fluorodeoxycytidine. Proc Natl Acad Sci 79:6419-6423.
13.
Boothman, D.A., Briggle, T.V., and Greer, S. (1989) Exploitation of elevated pyrimidine 
deaminating enzymes for selective chemotherapy.  Pharmac Ther 42:65-88. 
14.
Kaysen, J., Spriggs, D., and Kufe, D. (1986) Incorporation of 5-fluorodeoxycytidine and 
metabolites into nucleic acids of human MCF-7 breast carcinoma cells.  Cancer Res 
46:4534-4538.
15.
Momparler, R.L., Cote, S., and Eliopoulos N. (1997) Pharmacological approach for 
optimization of the dose schedule of 5-Aza-2'-deoxycytidine (Decitabine) for the therapy 
of leukemia.  Leukemia 11:175-80.
16.
Avramis, V.I., Mecum, R.A., Nyce, J., Steele, D.A., and Holcenberg, J.S. (1989) 
Pharmacodynamic and DNA methylation studies of high-dose 1-beta-D-arabino5-
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Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
FUnosyl cytosine before and after in vivo 5-azacytidine treatment in pediatric patients 
with refractory acute lymphocytic leukemia. Cancer Chemother Pharmacol 24:203-10.
17.
Smith, S.S., Kaplan, B.E., Sowers, L.C. and Newman, E.M. (1992) Mechanism of 
Human Methyl-Directed DNA Methyltransferase and the Fidelity of Cytosine 
Methylation.  Proc Natl Acad Sci 89: 4744-4748. 
18.
Camiener, G.W. (1968) Studies of the enzymatic deamination of ara-cytidine - V. 
Inhibition in vitro and in vivo by tetrahydrouridine and other reduced pyrimidine 
nucleosides.  Biochem Pharmacol 17:1981-1991.
19.
Kreis, W., Woodcock, T.M., Gordon, C.S., and Krakoff, I.H. (1977) Tetrahydrouridine: 
physiologic disposition and effect upon deamination of cytosine arabinoside in 
man.  Cancer Treat Rep 61:13471353.
20.
Wong, P.P., Currie, V.E., Mackey, R.W., Krakoff, I.H., Tan, C.T.C., Burchenal, J.H., and 
Young, C.W. (1979) Phase I evaluation of tetrahydrouridine combined with cytosine 
arabinoside.  Cancer Treat Rep 63:1245-1249.
21.
Camiener, G.W. and Smith, C.G. (1965) Studies of the enzymatic deamination of 
cytosine arabinoside - I. enzyme distribution and species specificity.  Biochem Pharmacol 
14:1405-1416.
22.
Kreis, W., Chan, K., Budman, D.R., et al. (1988) Effect of tetrahydrouridine on the 
clinical pharmacology of 1-ß-D-arabino5-FUnosylcytosine when both drugs are 
coinfused over three hours.  Cancer Res 48:1337-1342.
23.
Wempen, I., Duschinsky, R., Kaplan, L. and Fox, J.J. (1961) Thiation of Nucleosides. IV. 
The Synthesis of 5-Fluoro-2'-deoxycytidine and Related Compounds. J Am Chem Soc 
83:4755-4766.
24.
Kreis, W., Watanabe, K.A., and Fox, J.J. (1978) Structural requirements for the 
enzymatic deamination of cytosine nucleosides.  Helvetica Chimica Acta 61:1011-1016.
25.
Koshy, M., Dorn, L., Bressler, L., Molokie, R., Lavelle, D., Talischy, N., Hoffman, R., 
van Overveld, W., DeSimone, J. (2000) 2-Deoxy 5-azacytidine and fetal hemoglobin 
induction in sickle cell anemia. Blood 96:2379-2384. 
26.
Jan H. Beumer · Robert A. Parise · Edward M. Newman · James H. Doroshow · Timothy 
W. Synold · Heinz-Josef Lenz · Merrill J. Egorin, Concentrations of the DNA 
methyltransferase inhibitor 5-fluoro-2’-deoxycytidine (FdCyd) and its cytotoxic 
metabolites in plasma of patients treated with FdCydyd and tetrahydrouridine (THU), 
Cancer Chemother Pharmacol. (2008) 62:363–368
27.
Shields AF, Briston DA, Chandupatla S, Douglas KA, Lawhorn-Crews J, Collins JM, 
Mangner TJ, Heilbrun LK, Muzik O. A simplified analysis of [18F]3'-deoxy-3'-
fluorothymidine metabolism and retention. Eur J Nucl Med Mol Imaging. 2005 
Nov;32(11):1269-75. Epub 2005 Jul 1. Erratum in: Eur J Nucl Med Mol Imaging. 2007 
Apr;34(4):613.
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Protocol Number: CTEP 8865, NCI 12-C-0014
14 APPENDIX 1: PREPARATION OF TETRAHYDROURIDINE (THU) TUBES 
THU-containing tubes can be prepared using Tetrahydrouridine Injection (500 mg/50 ml), NSC 
112907. Each single use vial contains THU – 10 mg/ml, Sodium Phosphate dibasic, anhydrous, 
USP – 1.5 mg/ml, and Sodium Phosphate monobasic, monohydrate, USP – 0.4 mg/ml.  The 50-
ml vial should be divided into 1-ml aliquots and stored at 2 °C to 8 °C (refrigerated).  (The 1-ml
aliquots are not suitable for injection.) 
Using a 3/10 cc insulin syringe or other similar sized syringe with a fine needle, draw up 20 μl of 
the THU solution and transfer it to a 2-ml heparinized vacutainer tube (cat # 366664) by piercing 
the stopper. Do not draw up THU for more than one tube at a time. You will not be able to 
control the amount of THU solution that leaves the needle, as it is sucked out by the vacuum.  
Because of the fine needle, you will not lose the vacuum (apart from the volume added) in the 
collection tube. The THU-containing tubes may be prepared up to a day in advance.
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Abbreviated Title: [F-18] FdCyd Imaging
Version Date: 03-09-2015
Protocol Number: CTEP 8865, NCI 12-C-0014
15 APPENDIX 2:  PERFORMANCE STATUS SCALES/SCORES ECOG OR ZUBROD
SCALE KARNOFSKY SCORE
 
0
Asymptomatic and fully active 
100% 
1
Symptomatic; fully ambulatory; restricted in 
physically strenuous activity 
80-90% 
2
Symptomatic; ambulatory; capable of self-care; more 
than 50% of  waking hours are spent out of bed 
60-70% 
3
Symptomatic; limited self-care; spends more than 
50% of time in  bed, but not bedridden 
40-50% 
4
Completely disabled; no self-care; bedridden 
20-30% 
Page 39 of 39

ICF_001.pdf: 
MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• Adult Patient or 
• Parent, for Minor Patient 
INSTITUTE: 
National Cancer Institute 
STUDY NUMBER: 
12-C-0014 
PRINCIPAL INVESTIGATOR: 
Karen A. Kurdziel, M.D. 
STUDY TITLE:  
Phase 0 Trial of [F-18]-5-Fluoro-2'-Deoxycytidine with Tetrahydrouridine 
 
 
Continuing Review Approved by the IRB on 02/27/17 
Amendment Approved by the IRB on 03/18/15 (G) 
 
Date Sent to Web: 03/18/17 
IV FdCyd + THU 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent (1) 
 
 
INTRODUCTION 
We invite you to take part in a research study at the National Institutes of Health (NIH). 
First, we want you to know that: 
Taking part in NIH research is entirely voluntary.  
You may choose not to take part, or you may withdraw from the study at any time.  In 
either case, you will not lose any benefits to which you are otherwise entitled.  However, 
to receive care at the NIH, you must be taking part in a study or be under evaluation for 
study participation. 
You may receive no benefit from taking part.  The research may give us knowledge that 
may help people in the future. 
Second, some people have personal, religious or ethical beliefs that may limit the kinds of 
medical or research treatments they would want to receive (such as blood transfusions).  If you 
have such beliefs, please discuss them with your NIH doctors or research team before you agree 
to the study. 
Now we will describe this research study.  Before you decide to take part, please take as much 
time as you need to ask any questions and discuss this study with anyone at NIH, or with family, 
friends or your personal physician or other health professional.   
Why is this study being done?  
There is a treatment research study being done in patients with advanced cancer in which two 
experimental drugs are being given, FdCyd (also called 5-fluoro-2’-deoxcytidine), and THU 
(also called tetrahydrouridine).  You have agreed to participate in that treatment study.  There is 
not a lot of information known about how FdCyd works in the body.  Therefore, this study is 
being done to test if PET (Positron Emission Tomography) imaging with F-18 FdCyd (a 
radiolabeled version of the experimental treatment drug FdCyd) will give us information about 
how much of the treatment drug your tumor is taking up.  This will help us understand how 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0014 
CONTINUATION: page 2 of 9 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
FdCyd works in the body to fight cancer.  This is not a treatment study; participating in this 
study will not help in the treatment of your cancer.   
Why are you being asked to take part in this study? 
You are being asked to participate because you are enrolled in the treatment protocol entitled: A 
Multi-Histology Phase II Study of 5-Fluoro-2’-Deoxycytidine with Tetrahydrouridine (FdCyd + 
THU) NCI # 09-C-0214/CTEP # 8351 being performed in the Medical Oncology Branch, 
NCI/NIH.  Throughout this consent document, the treatment protocol will be referred to as 09-C-
0214/8351. 
How many people will take part in this Study?  
We expect to enroll 10-20 patients in this experimental imaging study. 
Description of Research Study 
Participation in this study involves undergoing 2 PET/CT imaging sessions, one before starting 
your treatment on 09-C-0214/8351, and one after you start treatment on 09-C-0214/8351.  The 
reason 2 imaging sessions are being done is to see if the quality of the images gets better after 
you have some of the treatment FdCyd in your body. 
What will happen if you take part in this research study?   
Before you begin the imaging study 
This study is being performed in conjunction with protocol 09-C-0214/8351 that you have 
enrolled in.  If you chose to participate in this imaging study, we will first make sure you are 
eligible.  To make sure it is safe to undergo the scans we will ask you some questions about your 
medical history and any allergies, if you are a woman able to get pregnant, we will also perform 
a pregnancy test (blood or urine) to make sure you are not pregnant, and ask you to sign this 
informed consent.  
During this imaging study 
Before beginning your first therapy dose of FdCyd on protocol 09-C-0214/8351, we will start 
giving you Tetrahydrouridine (THU), a compound that blocks the enzyme which breaks down 
FdCyd, through an IV (intravenous-small plastic tube placed in a vein in your arm).  There are 
no known side effects to THU at the dose levels you will be given, and this additional dose will 
NOT affect your future treatment with FdCyd + THU.  While the THU is being given to you, 
you will also receive a small amount of F-18 FdCyd.  This is a radiolabeled version of the 
therapy drug you will receive on 09-C-0214/8351.  The F-18 radiolabel acts as a tag, and lets us 
see on the PET/CT scan where the FdCyd goes in your body.   


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0014 
CONTINUATION: page 3 of 9 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
The F-18 FdCyd is given into your IV over about 1-3 minutes.  You should not feel anything 
during this time.  After you are given the F-18 FdCyd you will have a PET/CT scan.  You will 
need to lie still on your back on the scanning table for up to 75 minutes for the first scan and ~35 
minutes for an additional scan.  The PET/CT scan consists of a “low dose transmission” CT 
(sometimes called a CAT scan), followed by PET imaging.  The IV of THU will be continued 
throughout the scanning period and we will watch you closely for any side effects.   
This imaging procedure will be repeated on a separate day, while you are receiving your 
therapeutic infusion of FdCyd + THU on protocol 09-C-0214/8351. Repeat imaging will be 
performed 2-5 days after the initiation of FdCyd + THU therapy and at least 2 hours after dosing. 
When you are finished the Imaging Sessions 
When you are finished with each PET/CT imaging session, there are no restrictions on your diet 
or activity as a result of this protocol.  After you have completed the second imaging session you 
will be taken off this imaging study and will continue your participation on protocol 09-C-
0214/8351.  We may use the information from the protocol 09-C-0214/8351; we will compare 
how well the F-18 FdCyd went into the tumor with your tumor response after receiving the 
experimental treatment agents.  
What does this study involve? 
This study involves two F-18 FdCyd PET/CT imaging sessions, one performed during infusion 
of THU, and a second performed while receiving a treatment dose of FdCyd + THU as 
prescribed by the Phase 2 protocol.  You will be required to have an IV catheter put into a vein in 
your arm for each PET/CT imaging study.  You will need to lie still on the PET scan table for up 
to 2 hours during the imaging session.   
If you are a woman who is breast feeding or pregnant, you may not take part in the study because 
we don’t know how this medicine would affect your baby or your unborn child.  
Alternative Approaches or Treatments 
This is not a treatment study.  This study can only be performed in conjunction with your 
participation on protocol 09-C-0214/8351.  The alternative is to not participate.  If you choose 
not to participate in this imaging study, it will not affect your ability to participate in protocol 09-
C-0214/8351. 
What other choices do I have if I do not take part in this study?  
As this is not a treatment study, you can choose not to participate.   


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0014 
CONTINUATION: page 4 of 9 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
Will my medical information be kept private? 
We will do our best to make sure that the personal information in your medical record will be 
kept private.  However, we cannot guarantee total privacy.  Your personal information may be 
given out if required by law.  If information from this study is published or presented at scientific 
meetings, your name and other personal information will not be used. 
Organizations that may look at and/or copy your medical records for research, quality assurance, 
and data analysis include: 
• The National Cancer Institute (NCI) and other government agencies, like the Food and 
Drug Administration (FDA), involved in keeping research safe for people. 
Risks or Discomforts of Participation 
What side effects or risks can I expect from being in this study?  
Risks of FdCyd/THU 
 
COMMON, SOME MAY BE SERIOUS   
In 100 people receiving FdCyd/THU, more than 20 and up to 100 may have: 
• 
Anemia which may require blood transfusion 
• 
Diarrhea, nausea, vomiting 
• 
Tiredness 
• 
Bruising, bleeding 
• 
Infection, especially when white blood cell count is low 
• 
Loss of appetite 
 
OCCASIONAL, SOME MAY BE SERIOUS   
In 100 people receiving FdCyd/THU, from 4 to 20 may have: 
• 
Abnormal heartbeat 
• 
Bloating, constipation, heartburn, passing gas 
• 
Pain 
• 
Dry mouth, skin 
• 
Sores in mouth which may cause difficulty swallowing 
• 
Chills, fever 
• 
Swelling of arms, legs 
• 
Weight loss 
• 
Dehydration 
• 
Muscle weakness 
• 
Dizziness, headache 
• 
Changes in taste 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0014 
CONTINUATION: page 5 of 9 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
• 
Numbness, tingling or pain of the arms and legs 
• 
Cough, shortness of breath 
• 
Nose bleed 
• 
Hair loss, itching, rash 
• 
Increased sweating 
• 
Redness, pain or peeling of the palms and soles 
• 
Low blood pressure which may cause feeling faint 
Risks of FdCyd 
No adverse effects are expected from the small amount of F-18 FdCyd that will be administered 
under this protocol (for PET/CT imaging).  THU has no expected side effects at the dose used in 
this study and may increase the risk of experiencing FdCyd side effects.  Even though we do not 
anticipate adverse side effects, you should tell the doctors or nurses supervising the scan of any 
discomfort. 
Potential discomforts from the IV and injection of the radiotracer include 
o Mild pain and possible bruising at the injection site  
o Discomfort from lying on a hard surface for about 75 minutes 
o Infection at the IV site or infection in the blood  
o Leaking of the dose of F-18 FdCyd into the skin and tissue around the IV 
o Allergic reaction 
o Vasovagal reaction, a lowered blood pressure and heart rate during the IV insertion  
Risks of Radiation 
F-18 FdCyd is a radioactive tracer and you will receive a small amount radiation exposure that 
you would not otherwise receive.  Please note that this radiation exposure is not necessary for 
your medical care and is for research purposes only.  
Using the standard way of describing radiation dose, from participating in this study and 
undergoing a total of two F-18 FdCyd PET/CT imaging sessions (including radiation from the F-
18 FdCyd injection and low dose transmission scans), the amount of radiation exposure you will 
receive is equal to a uniform whole-body exposure of 3.5 rem, although each organ will receive a 
different dose.  This calculated value is known as the “effective dose” and is used to relate the 
dose received by each organ to a single value.  For comparison, the average person in the United 
States receives a radiation exposure of 0.3 rem per year from natural background sources, such 
as from the sun, outer space, and from radioactive materials that are found naturally in the earth’s 
air and soil.  The dose that you will receive from this research study is about the same amount 
you would normally receive in 11.7 years from these natural sources. The organs receiving the 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0014 
CONTINUATION: page 6 of 9 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
highest doses are the urinary bladder wall (15.3 rad), the surfaces of the bones (4.15 rads), and 
the liver (4.15 rads). 
The effects of radiation exposure on humans have been studied for over 60 years.  In fact, these 
studies are the most extensive ever done of any potentially harmful agent that could affect 
humans.  In all these studies, no harmful effects were ever observed from the levels of radiation 
you will receive by taking part in this research study.  However, scientists disagree on whether 
radiation doses at these levels are harmful.  Even though no effects have been observed, some 
scientists believe that radiation can be harmful at any dose - even low doses such as those 
received during this research.  
If you would like more information about radiation and examples of exposure levels from other 
sources, please ask the investigator for a copy of the pamphlet called, An Introduction to 
Radiation for NIH Research Subjects. Please tell your doctor if you have taken part in other 
research studies or received any medical care at the NIH or other places/hospitals that used 
radiation.  This way we can make sure that you will not receive too much radiation.  Consider x-
rays taken in radiology departments, cardiac catheterization, and fluoroscopy as well as nuclear 
medicine scans in which radioactive materials were injected into your body. 
When the medication is put through a vein in your arm, you may experience a moment of pain.  
In addition, there is the discomfort of having the catheter taped to your arm.  Other risks include 
bleeding, bruising, temporary clotting of the vein, and infection.  
Potential Benefits of Participation 
Are there benefits to taking part in this study?  
As this is NOT a treatment protocol, you will not to have any direct benefits; however, the result 
of this study may help doctor’s better understand how and how much FdCyd enters tumors, 
which may benefit other patients in the future who have cancer.   
Research Subject’s Rights 
What are the costs of taking part in this study?  
Participation in this research study is voluntary and you can withdraw at any time.  We 
encourage you to ask questions so you can make the most informed decisions during your 
participation in this study.  Refusal to participate will not result in penalty or less benefits to 
which you are otherwise entitled.  
It is important to stress that being in this protocol does not promise long-term medical care at the 
NIH Clinical Center.  If there is no further research study that is suitable for you and your state 
of disease, or if you are not currently on another research study, you will be returned to the care 
of your referring doctor or institution, or alternative sources of care closer to your home.  If you 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0014 
CONTINUATION: page 7 of 9 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
have any questions about your treatment in this protocol at NIH, you can contact the Principal 
Investigator, Dr. Karen A. Kurdziel (301-443-0622) or the patient care representative (301-496-
2626).  
If you choose to take part in the study, the following will apply, in keeping with the NIH policy: 
• 
Medicines that are not part of the study treatment will not be provided or 
paid for by the Clinical Center, NIH. 
• 
Once you have completed taking part in the study, medical care will no 
longer be provided by the Clinical Center, NIH. 
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. 
Stopping This Study 
Your doctor may decide to stop your participation in this study for the following reasons: 
• if he/she believes that it is in your best interest 
• if you are no longer participating in protocol 09-C-0214/8351 
• if you have side effects from the imaging sessions that your doctor thinks are too severe 
• if the imaging study is stopped for any reason. 
In this case, you will be informed of the reason therapy is being stopped. 
You can stop taking part in the study at any time. However, if you decide to stop taking part in 
the study, we would like you to talk to the study doctor and your regular doctor first. 
Conflict of Interest 
The National Institutes of Health (NIH) reviews NIH staff researchers at least yearly for conflicts 
of interest.  This process is detailed in a Protocol Review Guide.  You may ask your research 
team for a copy of the Protocol Review Guide or for more information.  Members of the research 
team who do not work for NIH are expected to follow these guidelines but they do not need to 
report their personal finances to the NIH. 
Members of the research team working on this study may have up to $15,000 of stock in the 
companies that make products used in this study.  This is allowed under federal rules and is not a 
conflict of interest.  
 


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
STUDY NUMBER: 
12-C-0014 
CONTINUATION: page 8 of 9 pages 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
(Continuation Sheet) 
• 
Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
 
File in Section 4:  Protocol Consent 
 
 
OTHER PERTINENT INFORMATION 
1. 
Confidentiality.  When results of an NIH research study are reported in medical journals 
or at scientific meetings, the people who take part are not named and identified.  In most cases, 
the NIH will not release any information about your research involvement without your written 
permission.  However, if you sign a release of information form, for example, for an insurance 
company, the NIH will give the insurance company information from your medical record.  This 
information might affect (either favorably or unfavorably) the willingness of the insurance 
company to sell you insurance. 
The Federal Privacy Act protects the confidentiality of your NIH medical records.  However, you 
should know that the Act allows release of some information from your medical record without 
your permission, for example, if it is required by the Food and Drug Administration (FDA), 
members of Congress, law enforcement officials, or authorized hospital accreditation 
organizations. 
2. 
Policy Regarding Research-Related Injuries.  The Clinical Center will provide short-
term medical care for any injury resulting from your participation in research here.  In general, 
no long-term medical care or financial compensation for research-related injuries will be 
provided by the National Institutes of Health, the Clinical Center, or the Federal Government.  
However, you have the right to pursue legal remedy if you believe that your injury justifies such 
action. 
3. 
Payments.  The amount of payment to research volunteers is guided by the National 
Institutes of Health policies.  In general, patients are not paid for taking part in research studies at 
the National Institutes of Health.  Reimbursement of travel and subsistence will be offered 
consistent with NIH guidelines. 
4. 
Problems or Questions.  If you have any problems or questions about this study, or 
about your rights as a research participant, or about any research-related injury, contact the 
Principal Investigator, Karen A. Kurdziel, M.D., Building 10, Room B3B403, Telephone:  301-
443-0622. You may also call the Clinical Center Patient Representative at (301) 496-2626.  
5. 
Consent Document.  Please keep a copy of this document in case you want to read it 
again.


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
STUDY NUMBER: 
12-C-0014 
CONTINUATION: page 9 of 9 pages 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
(Continuation Sheet) 
• 
Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
 
File in Section 4:  Protocol Consent 
 
 
 
COMPLETE APPROPRIATE ITEM(S) BELOW: 
A. Adult Patient’s Consent 
B. Parent’s Permission for Minor Patient. 
I have read the explanation about this study 
and have been given the opportunity to discuss 
it and to ask questions.  I hereby consent to 
take part in this study. 
I have read the explanation about this study 
and have been given the opportunity to discuss 
it and to ask questions.  I hereby give 
permission for my child to take part in this 
study.   
(Attach NIH 2514-2, Minor’s Assent, if 
applicable.) 
 
  
  
 
 
 
Signature of Adult Patient/ 
Legal Representative 
Date 
Signature of Parent(s)/ Guardian Date 
 
 
Print Name 
 
 
Print Name 
C. Child’s Verbal Assent (If Applicable) 
The information in the above consent was described to my child and my child agrees to 
participate in the study. 
 
  
  
 
Signature of Parent(s)/Guardian 
Date 
Print Name 
THIS CONSENT DOCUMENT HAS BEEN APPROVED FOR USE  
FROM FEBRUARY 27, 2017 THROUGH FEBRUARY 26, 2018. 
 
 
 
 
 
 
 
 
Signature of Investigator 
Date 
Signature of Witness 
Date 
 
 
Print Name 
 
 
Print Name