Clinical trial: NCT01479348
Section: Alternatives
Subsections: Alternative Approaches Or Treatments|What Other Choices Do I Have If I Do Not Take Part In This Study?

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.

As this is not a treatment study, you can choose not to participate.  
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  
STUDY NUMBER: 12-C-0014 CONTINUATION: page 4 of 9 pages
Clinical trial: NCT01479348
Section: Confidentiality
Subsections: 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.
Clinical trial: NCT01479348
Section: Participant's Rights
Subsections: 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  
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  
STUDY NUMBER: 12-C-0014 CONTINUATION: page 7 of 9 pages 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 (301-4962626). 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.
Clinical trial: NCT01479348
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Risks Of Fdcyd/Thu|Risks Of Fdcyd|Risks Of Radiation|Potential Benefits Of Participation Are There Benefits To Taking Part In This Study?

| 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                                         |  
| 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                                                                                                          |
| 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 |  
STUDY NUMBER: 12-C-0014 CONTINUATION: page 5 of 9 pages  
| -   | 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  |

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

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 F18 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  
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  
STUDY NUMBER: 12-C-0014 CONTINUATION: page 6 of 9 pages 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 xrays 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.

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.
Clinical trial: NCT01479348
Section: Procedures
Subsections: What Will Happen If You **Take Part In This Research Study?**|What Does This Study Involve?

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.  
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  
STUDY NUMBER: 12-C-0014 CONTINUATION: page 3 of 9 pages 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-C0214/8351. 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.

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.
Clinical trial: NCT01479348
Section: Purpose of Research
Subsections: Why Is This Study Being Done?|Why Are You Being Asked To Take Part In This Study?

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  
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)  
STUDY NUMBER: 12-C-0014 CONTINUATION: page 2 of 9 pages 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.

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-C0214/8351.
Clinical trial: NCT01479348
Section: Withdrawal from Study
Subsections: 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.