Clinical trial: NCT00978250
Section: Alternatives
Subsections: What Other Choices Do I Have If I Do Not Take Part In This Study?

Talk to your doctor about your choices before you decide if you will take part in this study. Your other choices may include:  
- Getting other therapies that, although might not improve survival, may have other benefits, such as delaying disease progression.  
- Taking part in another study.  
- Getting no treatment. - Getting comfort care, also called palliative care. This type of care helps reduce pain, tiredness, appetite problems, and other problems caused by cancer. It does not treat the cancer directly, but instead tries to improve how you feel. Comfort care tries to keep you as active and comfortable as possible.
Clinical trial: NCT00978250
Section: Confidentiality
Subsections: Will My Medical Information Be Kept Private?|Use Of Specimens And Data For Future Research|Certificate Of Confidentiality

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.  
- Designated investigators from other cancer centers participating in this study, including the City of Hope National Medical Center; the City of Hope Medical Group, Pasadena; the University of Southern California/Norris Comprehensive Cancer Center; and the University of California, Davis Cancer Center.
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.  
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We would like to keep some of your specimens and data that we collect and use them for future research and share them with other researchers. We will not contact you to ask about each of these future uses. These specimens and data will be identified by a number and not your name. Your specimens and data will be used for research purposes only and will not benefit you. Researchers use specimens and data stored in scientific databases to advance science and learn about health and disease. It is also possible that the stored specimens and data may never be used. Results of research done on your specimens and data will not be available to you or your doctor. It might help people who have cancer and other diseases in the future. If you decide now that your specimens and data can be kept for research and shared, you can change your mind at any time. Just contact us and let us know that you do not want us to use your specimens and/or data. Then any specimens that have not already been used or shared will be destroyed and your data will not be used for future research. Please read the sentence below and think about your choice. After reading the sentence, circle and initial the answer that is right for you. No matter what you decide to do, it will not affect your care. My specimens and data may be kept and shared for use in research to learn about, prevent, or treat cancer or other health problems. Yes No Initials_________

To help us protect your privacy, we have obtained a Certificate of Confidentiality. The researchers can use this Certificate to legally refuse to disclose information that may identify you in any federal, state, or local civil, criminal, administrative, legislative, or other proceedings, for example, if there is a court subpoena. The researchers will use the Certificate to resist any demands for information that would identify you, except as explained below.  
You should also know that there are several circumstances in which the Certificate does not provide coverage. These include when information:
- will be used for auditing or program evaluation internally by the NIH; or - must be disclosed to meet the legal requirements of the federal Food and Drug Administration (FDA).  
- is necessary for your medical treatment and you have consented to this disclosure;
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- is for other research.  
In addition, identifiable, sensitive information protected by this Certificate cannot be admissible as evidence or used for any purpose in any action, suit, or proceeding without your consent. You should understand that a Certificate of Confidentiality does not prevent you or a member of your family from voluntarily releasing information about yourself or your involvement in this research. If an insurer, employer, or other person obtains your written consent to receive research information, then the researchers will not use the Certificate to withhold that information. The Certificate of Confidentiality will not protect against the required reporting by hospital staff of information on suspected child abuse, reportable communicable diseases, and/or possible threat of harm to self or others.
Clinical trial: NCT00978250
Section: Participant's Rights
Subsections: What Are My Rights If I Take Part In This Study?

Taking part in this study is your choice. You may choose either to take part or not to take part in this study. If you decide to participate, you may leave the study at any time. No matter what decision you make, there will be no penalty to you, and you will not lose any of your regular benefits. Leaving the study will not affect your medical care. You can still get your medical care from our institution if you are eligible and choose to participate in another trial. We will tell you about new information or changes in the study that may affect your health or your willingness to continue in the study. In the case of injury resulting from this study, you do not lose any of your legal rights to seek payment by signing this form.
Clinical trial: NCT00978250
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: What Side Effects Or Risks Can I Expect From Being In The Study?|Potential Risks Related To Research-Related Imaging Studies:

If you choose to take part in this study, there is a risk that you may:
- Lose time at work or home and spend more time in the hospital or doctor's office than usual
- Be asked sensitive or private questions which you normally do not discuss
The agents used in this study may affect how different parts of your body work such as your liver, kidneys, heart, and blood. The study doctor will be testing your blood and will let you know if changes occur that may affect your health. There is also a risk that you could have side effects from the study drug(s)/study approach. Here are important points about side effects:
- The study doctors do not know who will or will not have side effects.  
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- Some side effects may go away soon, some may last a long time, or some may never go away.  
- Some side effects may interfere with your ability to have children. - Some side effects may be serious and may even result in death.
Here are important points about how you and the study doctor can make side effects less of a problem:
- Tell the study doctor if you notice or feel anything different so they can see if you are having a side effect.  
- The study doctor may be able to treat some side effects.  
- The study doctor may adjust the study drugs to try to reduce side effects.  
The tables below show the most common and the most serious side effects that researchers know about. There might be other side effects that researchers do not yet know about. If important new side effects are found, the study doctor will discuss these with you. Risks and side effects related to FdCyd with THU may include:  
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
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- Muscle weakness  
  
  
- Dizziness, headache - 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
THU has no expected side effects at the dose used in this study, but THU may make the side effects of FdCyd worse. Blood draws for routine laboratory tests may result in bruising, infection, and minor pain or discomfort comparable with a needle prick. 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. The removal of tumor tissue for research biopsies can cause pain, bruising, and possibly infection at the site where the biopsy was taken. The biopsy procedure will be discussed in detail with you, including side effects, and we will ask you to sign a separate consent form before to the procedure.  
Reproductive Risks: Because the drugs in this study can possibly affect unborn babies and infants, you should not become pregnant, father a baby, or breastfeed while you are on this study. Women of childbearing potential will be required to have a pregnancy test. If you are a woman who can become pregnant, or are the partner of a woman who can become pregnant, you will need to practice an effective form of birth control before starting study treatment and for 3 months after you finish study treatment. If you think that you or your partner is pregnant, you should tell your study doctor or nurse at once. Avoiding sexual activity is the only certain method to prevent pregnancy. But, if you choose to be sexually active, you should use an appropriate "double barrier" method of birth control (such as female use of a diaphragm, intrauterine device (IUD), or contraceptive sponge, in addition to male use of a condom) or the female should be using prescribed "birth control" pills, injections, or implants. Male participants must also use adequate contraception. If you choose to be sexually active during this study, you understand that even with use of these birth control measures pregnancy could still result. Some methods might not be approved for use in this study. Ask about counseling and more STUDY NUMBER: 09-C-0214 CONTINUATION: page 9 of 15 pages information about preventing pregnancy. For more information about risks and side effects, ask your study team.

This research study involves exposure to radiation from up to 2 CT scans (used in biopsy collections). This radiation exposure is not required for your medical care and is for research purposes only. The amount of radiation you will receive in this study is 1.6 rem, which is below the guideline of 5 rem per year allowed for research subjects by the NIH Radiation Safety Committee. The average person in the United States receives a radiation exposure of 0.3 rem per year from natural sources, such as the sun, outer space, and the earth's air and soil. If you would like more information about radiation, please ask the investigator for a copy of the pamphlet, An Introduction to Radiation for NIH Research Subjects. While there is no direct evidence that the amount of exposure received from participating in this study is harmful, there is indirect evidence it may not be completely safe. There may be a very slight increase in the risk of cancer. Please tell your doctor if you have had any radiation exposure in the past year, either from other research studies or from medical tests or care, so we can make sure that you will not receive too much radiation. Radiation exposure includes 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. If you are pregnant you will not be permitted to participate in this research study. If you are breast feeding and the protocol involves injection of radioactive material you will not be permitted to participate. It is best to avoid radiation exposure to unborn or nursing infants since they are more sensitive to radiation than adults.
Clinical trial: NCT00978250
Section: Procedures
Subsections: What Will Happen If I Take Part In This Study?|Tests And Procedures That Are Either Being Tested In This Study Or Being Done To See How The Drug Is Affecting Your Body:

If you are accepted and you choose to take part, you will begin receiving FdCyd and THU. Please see the Study Chart below for more details. You will also have tests and procedures done because you are in the study to see how FdCyd and THU are affecting your body. This will include repeating some of the imaging studies (e.g., CT scans, a computerized x-ray examination) to find out if your cancer has responded. Descriptions of the tests and procedures that will be performed during the study are listed below. FdCyd and THU will be given in cycles. Each cycle is 28 days long. You will receive FdCyd and THU on days 1-5 and 8-12 of each cycle. You may continue to receive FdCyd and THU if your cancer does not grow, if you do not have too many side effects, and if you are willing to do so. Clinical Center Visits: FdCyd and THU will be given through a vein each day on days 1-5 and 812 of each cycle. We will ask that you come to the Clinical Center on these days during each cycle. While you are at the Clinical Center we will perform study tests and procedures to see how the study drugs are affecting your body. So, for each cycle you will be coming to the STUDY NUMBER: 09-C-0214 CONTINUATION: page 3 of 15 pages Clinical Center for at least 12-14 days. If you develop any side effects, you may be asked to visit more often. Standard procedures being done because you are in this study; these may be done more often because you are in the study:
- **Clinic visit:** to ask how you are feeling and to evaluate you with a physical examination every week during Cycle 1, and then at the beginning of each cycle.  
- **Vital signs and physical examinations:** will be performed during the clinic visits. - **Blood tests:** Measurement of your white blood cells, red blood cells, and platelets and measurements of your blood sugar and electrolytes and of how your liver, kidneys, and blood clotting work will be done every week during Cycle 1, and then before treatment on weeks 1 and 2 of all other cycles. Approximately 1 tablespoon (15 mL) of blood will be drawn per visit.  
- **Urine test:** Depending on the results of blood tests, you may be asked to collect your urine for 24 hours for further testing.  
- **CT scans** or other imaging tests such as ultrasound (an examination using sound waves) or MRI (an examination using magnetic field and radio waves) that detect your tumor will be done before the study and every 8 weeks while you are receiving study drugs (less often if you have been on study for more than one year). This is done so that any benefit of the treatment can be determined, and if your cancer is not responding to the treatment, the study team can tell you and discuss other treatment options (discussed further below).

- **Measurement of FdCyd and THU in your blood:** We will collect blood samples from some patients to measure the amount of study drugs in the blood and to help us find out how the body handles the drugs. Blood will be collected during Cycle 1 only, on day 1 before the drugs are given, at multiple time points while the drugs are being given, at several times up to 6 hours after the drugs are given, and then once before treatment on days 2, 3, 4, and 5. The total blood for all these tests will be about 3 tablespoons (45 mL).  
- **Other research blood samples:** We will also be collecting blood samples to find out the effects of the drugs on cells in your blood. Blood samples will be collected on days 1, 2, and 12 in Cycle 1, on day 1 of Cycle 2 and every subsequent cycle, on day 12 in Cycles 2, 4, and 6, and, if your disease comes back, at the time that your disease comes back. The total blood for all these tests will be about 1/2 a cup (about 115 mL).  
- **Measurement of FdCyd and THU in your urine:** We will collect urine samples from some patients to measure the amount of study drugs in the urine. Urine will be collected before the study drugs are given and for 24 hours after the drugs are given on Cycle 1, day 1.  
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- **Tumor biopsies:** After you are accepted to take part in the study, you will be asked to have a biopsy of your tumor (removal of a small bit of tissue for examination under a microscope) once before you receive study drugs and a second time after you complete Cycle 2. We are collecting biopsy samples to study how the drugs affect your tumor. Biopsies are a very important part of this trial and are done for research purposes. Tumor biopsies are optional, and no more than two biopsy procedures will be performed during the study. You may choose not to have tumor biopsies, and this will not affect your taking part in this study. If you decide not to have tumor biopsies, you will still receive study drugs and have other tests that are part of the study. Tumor biopsies are only collected by trained personnel. Biopsies are collected using a small core needle under imaging guidance (CT, MRI, or ultrasound as considered appropriate by the interventional radiologist performing the biopsy). Imaging helps the specialized radiologist know that the needle has been placed into the tumor mass. Typical risks of biopsy collection include, but are not limited to, bleeding, infection, pain, and scarring. If you experience any complications from the biopsy, medical care will be offered to you. You will be counseled in more detail about biopsies, and you will be asked to sign a separate consent form that will describe the procedures and risks at that time. Your safety is the most important thing at all times. If upon attempting the first biopsy, no tissue can be obtained or it has caused you harm, the second biopsy procedure will not be done. After you are enrolled in this study, if for any reason the biopsies cannot be done safely, you may still receive the study drugs but the biopsies will not be done.  
I agree to allow biopsies for research purposes Yes____ No____
Initials_________
Clinical trial: NCT00978250
Section: Purpose of Research
Subsections: Why Is The Study Being Done?|Are There Benefits To Taking Part In This Study?

This research study includes patients with advanced non-small cell lung cancer, breast cancer, bladder cancer, and head and neck cancer. You are being asked to volunteer to take part in this research study because you have advanced cancer that has progressed after receiving standard treatment or for which no effective therapy exists. We are doing this study to try to develop better treatments for cancer. On this study, two experimental drugs, FdCyd (also called 5fluoro-2'-deoxcytidine), and THU (also called tetrahydrouridine), will be given to you. The purpose of this study is to see if the drugs work together to control your tumor growth. FdCyd is thought to work by changing how genes work in cancer cells. THU does not have any anticancer effects on its own, but it helps keep the other drug, FdCyd, from being broken down by your body. These drugs have been given to more than 170 patients as of February 2016. The two drugs have some side effects that will be reviewed with you by your medical team before you sign the consent form.

Taking part in this study may or may not make your health better. While doctors hope the combination of FdCyd and THU will be useful against your cancer, there is no proof of this yet. You should discuss other treatment options with the study team and your home doctor before deciding to take part in this study. We do know that information from this study will help doctors learn more about the combination of FdCyd and THU as a treatment for cancer. This information will also help future cancer patients.  
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Clinical trial: NCT00978250
Section: Withdrawal from Study
Subsections: Are There Reasons That My Taking Part In This Study May End Early?|Stopping Therapy

Your study doctor will be watching you and your cancer while you are receiving FdCyd and THU. If your cancer is worsening, the study doctor will suggest that you stop taking the drugs and she or he will discuss other options with you. Also, if you are having side effects from the drugs which are dangerous to your health or too difficult for you to tolerate, you and the study team may decide that you should stop taking the drugs. The study doctor may stop you from taking part in this study at any time if he or she believes it is not in your best interest, if you do not follow the study rules, or if the study is stopped.

Your doctor may decide to stop your therapy for the following reasons:
- if he/she believes that it is in your best interest
- if your disease comes back during treatment - if you have side effects from the treatment that your doctor thinks are too severe
- if new information shows that another treatment would be better for you
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. If you decide at any time to withdraw your consent to participate in the trial, we will not collect any additional medical information about you. However, according to FDA guidelines, information collected on you up to that point may still be provided to the Cancer Therapy Evaluation Program (CTEP) at the National Cancer Institute (NCI) or designated representatives. If you withdraw your consent and leave the trial, any samples of yours that have been obtained for the study and stored at the NCI can be destroyed upon request. However, any samples and data generated from the samples that have already been distributed to other researchers or placed in the research databases **cannot** be recalled and destroyed.