Clinical trial: NCT00436956
Section: Alternatives
Subsections: Alternative Approaches Or Treatments

What other choices do I have if I do not take part in this study?  
To make an informed decision about whether or not to participate in this study, you need to know your options. Alternative treatments to this study, in general, include:
1) no further treatment of the cancer, but treatment of any symptoms that may be causing discomfort, this type of care helps reduce pain, tiredness, appetite problems and other problems caused by the cancer. It does not treat the cancer directly. Instead, it tries to improve how you feel. Comfort care tries to keep you as active and comfortable as possible. 2) chemotherapy and/or hormonal therapy with commercially available drugs. Recent studies have shown that a drug known as docetaxel or taxotere in combination with prednisone has survival benefit in prostate cancer. This is now recognized as the standard treatment of prostate cancers that are no longer sensitive to hormonal therapies. You are required to have at least one attempt at cytotoxic therapy for your prostate cancer before enrolling on this study; you remain eligible for this study after several attempts at different types of cytotoxic therapy. 3) ketoconazole 4) other experimental therapies, 5) radiation therapy to shrink tumor masses or relieve pain, and 6) surgery to remove tumor masses.  
All of these options may not apply to your particular situation, but it is important that you have explored these options with your regular doctor.
Clinical trial: NCT00436956
Section: Confidentiality
Subsections: Research Subjects' Rights Will Your 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),
which are involved in keeping research safe for people.  
- Qualified representatives from AstraZeneca Pharamceuticals, the pharmaceutical drug sponsors who produce AZD2171.  
Please note: This section of the informed consent form is about additional research studies that are being done with people who are taking part in the main study. You may take part in these additional studies if you want to. You can still be a part of the main study even if you say 'no' to taking part in any of these additional studies. You can say "yes" or "no" to each of the following studies. Please mark your choice for each study.
Clinical trial: NCT00436956
Section: Duration of Study Involvement
Subsections: Before You Begin The Study …|During The Study …|When You Are Finished Taking Azd2171|How Long Will You Be In The Study?

You will need to have the following exams, tests, and procedures to find out if it is safe for you to be in the study. The exams, tests, and procedures are part of regular cancer care and may be done even if you do not join the study. If you recently had some of the tests, they may not need to be repeated. This will be up to your study team.  
- Blood tests: measurements of how your liver and kidneys work, measurement of your white blood cells, red blood cells and platelets, your blood sugar and blood electrolytes.  
- Computerized Tomography scan of the chest, abdomen, and pelvis within the past 4 weeks - Bone scan within the past 4 weeks - Chest x-ray within the past 4 weeks - Blood counts and chemistries (within 16 days before enrollment) - PSA (Prostate Specific Antigen); if PSA is less than 4 ng/ml: PAP (prostate acid phosphatase) within 7 days of enrollment
- Tumor biopsy (optional) - Electrocardiogram - Echocardiogram

If the exams, tests and procedures show that you can be in the study, and you choose to take part, then you will need the following tests and procedures. Some are part of regular cancer care; other tests are specific to the drug you will be taking.  
- Blood tests including blood counts, chemistries, Thyroid Stimulating Hormone, and serum troponin. - Electrocardiogram - PSA measurements - Urinalysis for protein.  
You will need these tests and procedures that are also part of regular cancer care. They are being done more often because you are in this study.  
- Computerized Tomography scan of the chest, abdomen, and pelvis and Echocardiogram after cycles 2 and 4, then every 3 months.  
- Bone scan after cycles 2 and 4, then every 3 months.  
You will need these tests and procedures that are either being tested in this study or being done to see how the study drug is affecting your body.  
- Pharmacokinetic sampling- this is determination of the amount of AZD2171 in your bloodstream at different amounts of time after having consumed the drug by mouth.  
- Optional tumor biopsies before AZD2171 and after 2 and 6 cycles of experimental treatment.  
Continue to record all doses of AZD2171 taken and / or missed in your pill diary. Record your blood pressure at least once daily in a blood pressure diary, which will be provided to you. We will also provide you with a blood pressure monitor.

Your participation in this study will continue until either you or your study team decides that this medication is not beneficial to you. Your participation is voluntary; so you may stop taking AZD2171 at any time, but we ask that you speak to your study team before stopping the study drug. Your study team will be monitoring you and your cancer while  
STUDY NUMBER: 07-C-0059 CONTINUATION: page 4 of 12 pages you are taking AZD2171. If your prostate cancer is clearly worsening, then your study team will stop treatment with AZD2171. At the end of the study, no additional testing will be required.

You will be invited to continue to take AZD2171 until your study team advises you that the medication is not helping your cancer, you are experiencing significant toxicity from the therapy, or you decide that you no longer wish to participate in the study.
Clinical trial: NCT00436956
Section: Participant's Rights
Subsections: What Are Your Rights If You Take Part In This Study?

Taking part in this study is your choice. You may choose either to take part or to not take part in the study. If you decide to take part in this study, 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. 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: NCT00436956
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Risk Or Discomforts Of Participation What Side Effects Or Risks Can You Expect From Being In The Study?|Potential Benefit Are There Benefits To Taking Part In The Study?|Risks

You may have side effects while you are taking the study drug. Everyone taking part in the study will be watched carefully for any side effects. However, doctors don't know all the side effects that may happen so it is important to report changes that you may notice, even if your study team does not ask specifically about them. Side effects may be mild or very serious. Your study team may give you medicines to help lessen side effects. Many side effects go away with those medicines and others can go away soon after you stop taking AZD2171. In some cases, side effects can be  
STUDY NUMBER: 07-C-0059 CONTINUATION: page 6 of 12 pages serious, long lasting, or may never go away. There are no known long-lasting toxicities from AZD2171 at this time. You should talk to your study team about all side effects that you have while taking part in the study. Preliminary studies have shown hypertension, or elevated blood pressure, to be one common side effect of AZD2171. Your blood pressure will be closely monitored while you are taking AZD2171. If your blood pressure becomes elevated while taking AZD2171, your physicians may recommend follow-up with your primary care physician, starting or increasing medication to lower blood pressure, and / or home blood pressure monitoring. Grapefruit juice has been shown to interact with a number of drugs by blocking the activity of the body's cytochrome P450 (CYP450) system. CYP450 is important in breaking down substances in the body, including many drugs. Since the degree to which grapefruit juice interacts with AZD2171 in the body is not fully known, please avoid grapefruit juice while taking AZD2171. As other drugs may also interact with the CYP450 system, please contact the study team prior to starting any new medication.  
| Risks and side effects related to AZD2171 include those which are: Side Effect Mild Severe, but not life threatening   | Life threatening                                                                                                                                                                                                                                                                                |
|------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Common                                                                                                                 | High blood pressure  (Hypertension) Diarrhea (can be  severe in some cases) Fatigue Loss of appetite  (Anorexia) Hoarseness, loss or  alteration in voice,  throat irritation  (laryngitis)                                                                                                     |
| Uncommon                                                                                                               | Red peeling rash  affecting the hands  and feet (hand-foot  syndrome) Abnormal blood tests  related to liver  function Dry mouth Headache (can be  severe in some cases) Constipation  Weight loss Cough Sweating Low thyroid function  (with associated  inreased thyroid  stimulating hormone |  
Risks and side effects related to AZD2171 are detailed in the table on the following page. "Common" side effects as those occurring in greater than 20% of patients and "Uncommon" side effects as those occurring in ≤ 20% of patients.  
NIH 2514-2, Minor Patient's Assent to Participate In A Clinical Research Study  
| STUDY NUMBER:                                                                                                                                                                                                                                                                                                                                                    | 07-C-0059    | CONTINUATION: page 7 of 12 pages                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      |                                                                                                                                                                                                                         |
|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| and decreased  thyroxine levels) Dehydration Proteinuria (protein in  the urine) Difficulty swallowing  (dysphagia) Mouth ulcers  (mucositis)  Muscle pain Fever , Back pain,  Joint pain, Muscle pain Nausea Vomiting  Shortness of breath Dry Skin Abdominal Pain Decreased platelets  Bladder spasms  Low red blood cells  causing anemia  Low blood pressure |              |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       |                                                                                                                                                                                                                         |
| Rare                                                                                                                                                                                                                                                                                                                                                             | Hypokalemia* | Duodenal ulcer (stomach ulcer)* Aphasia (inability to speak)* Hepatic hemorrhage (bleeding into the liver)* Abnormal EKG (prolonged QT corrected)* Muscle weakness* Transient ischemic attack ("ministroke")* Deep vein thrombosis (blood clots)* Left ventricular systolic dysfunction (decrease in  heart function) Formation or presence of a blood clot inside an artery Leukoencephalopathy syndrome including reversible  posterior leukoencephalopathy syndrome (RPLS).  RPLS is a medical condition related to leakiness of  blood vessels in the brain and can cause confusion,  blindness or vision changes, seizure and other  symptoms, as well as changes in brain scans. This  condition is usually reversible, but in rare cases it is  potentially life-threatening and may have long-term  effect on brain function. | Low blood sugar* Stroke* Hypertensive crisis (severe high blood  pressure)  Lung  infection/pneumonia*  Bleeding into you  spine or brain(Central  Nervous System Hemorrhage)*  Death*  Kidney Failure(Renal  Failure)* |
| *Duodenal ulcer (stomach ulcer), Hepatic hemorrhage (bleeding into the liver), transient ischemic attack (ministroke),                                                                                                                                                                                                                                           |              |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       |                                                                                                                                                                                                                         |  
*Duodenal ulcer (stomach ulcer), Hepatic hemorrhage (bleeding into the liver), transient ischemic attack (ministroke), deep vein thrombosis (blood clots), low blood sugar, abnormal EKG (prolonged QT corrected), muscle weakness, aphasia (inability to speak), Low Potassium (Hypokalemia), Lung infection/pneumonia, Bleeding into you spine or brain(Central Nervous System Hemorrhage)* , Death, Kidney Failure (Renal Failure) and stroke are classified as rare side effects of  
STUDY NUMBER: 07-C-0059 CONTINUATION: page 8 of 12 pages AZD2171. These events have occurred on AZD2171 trials but it has not yet been determined whether the events were caused by AZD2171. Reproductive risks: You should not father a baby while on this study because the drugs in this study can affect an unborn baby. It is important you understand that you must refrain from intercourse or need to use birth control while on this study. Check with your study doctor about what kind of birth control methods to use and for how long you should use them after you are no longer receiving the study drug. Typical birth control methods include abstinence from intercourse, barrier contraceptives (condoms, diaphragms), or hormonal agents (oral contraceptive pills). For more information about risks and side effects, ask your study team.  
AZD2171 can cause hypertension that can become significant. For the first 4 weeks of the study you will be required to have your blood pressure checked at a healthcare facility. This should be recorded in your first study diary and reported to the research team. You will also begin taking prednisone by mouth at a dose of 10 mg on the first day of each cycle but you will continue to take it daily throughout the cycle. The side effects that have been associated with prednisone include:
•gastric hyperacidity(increased stomach acid), increased appetite, insomnia or nervousness occurring in > 10% of patients •hyperglycemia (high blood sugar level), fluid retention, mood swings, dizziness, headaches, muscle weakness, osteoporosis (bone thinning), and cataracts with long-term use, occurring in about 1% - 10% of patients *Hypertension occurring in < 1% of patients but this risk may be higher in combination with AZD2171. In addition,this combination of prednisone and AZD-2171 has not been studied before so unknown side effects may also occur. The DCE-MRI involves intravenous injection with a special non-radioactive dye (gadolinium chelate) to examine blood flow in a certain part of the body. An intravenous injection involves a needle stick into a vein in the arm. Several attempts may be necessary to place the needle into the vein. In addition to the pain associated with the needle stick there may be some bruising after the needle is removed. Experience with a large number of patients who have received commercially available gadolinium has shown it is without side effects in a large majority of patients. When side effects do occur, they are usually mild and last a short time. These include coolness in the arm during injection, headache, and nausea. More severe reactions (shortness of breath, wheezing, or lowering of blood pressure) have occurred in an extremely small number of patients. Side effects may be mild or very serious. Many side effects go away soon after you stop taking AZD2171. In some cases side effects may be long lasting or may never go away. There also is a risk of death.  
NIH 2514-2, Minor Patient's Assent to Participate In A Clinical Research Study STUDY NUMBER: 07-C-0059 CONTINUATION: page 9 of 12 pages

Taking part in this study may or may not make your health better. While doctors hope AZD2171 will be more useful against cancer compared to currently available treatments, there is not yet any proof that this is so. We do know that the information from this study will help doctors learn more about AZD2171 as a treatment for cancer. The information will help future cancer patients.

The greatest risk to you is the release of information from your health records. We will do our best to make sure that your personal information will be kept private. The chance that this information will be given to someone else is very small.
Clinical trial: NCT00436956
Section: Procedures
Subsections: What Will Happen If You Take Part In This Research Study?

This drug is a medicine you take by mouth and give to yourself every day. You will start by taking 1 tablet once daily. You are to swallow the tablet whole with about 8 oz. of water each morning, on an empty stomach, one hour before or two hours after meals. You should record the number of pills you consume and the time of consumption in a diary which will be provided to you by your study team. If you miss doses, that should also be recorded in the diary. If you remember your missed dose within three hours of the time you usually take a dose, you may take a pill to make up for the missed dose; otherwise do not make up the missed dose. The dose will be adjusted if you experience any significant problems. This will be determined by your study team. AZD2171 can be taken while you are an outpatient. To help us to understand how the drug is working, a number of tests will be done, including tests to determine the level of vascular endothelial growth factor receptor (VEGFR), the target of AZD2171, in your blood prior to cycle 1 and monthly thereafter, as well as a special type of MRI (dynamic contrast-enhanced MRI, DCE-MRI, lasting approximately one hour) to evaluate blood flow, and tumor biopsies (optional), both before and after 2 and 6 cycles of treatment. You will be watched very closely as an outpatient and every 4 weeks return to the NIH to see a doctor who will monitor your response to the experimental treatment. At the outset of the study you may be hospitalized for 24 to 48 hours to complete research studies including your biopsies and blood measurements to determine the level of drug in your bloodstream. During this hospitalization, blood will be drawn immediately prior to your first dose, and 0.25 hr, 0.5 hr, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr, and 48 hours after ingestion. You will also have blood drawn at each clinic visit to measure the level of drug in your body. Each blood draw will consist of approximately one tablespoon of blood. In addition, you will be asked to take your blood pressure twice daily (once in the morning while resting quietly, once in the evening) and record it in a log which will be provided to you. Furthermore, all study participants will be invited to provide a blood sample (approximately one tablespoon) for retrospective evaluation of genetic variants possibly playing a role in how the drug acts. Participation in pharmacogenetic studies will be optional for all patients entering the study.  
In addition, you will also take prednisone 10 mg per day. This drug is prescribed with FDA approved prostate cancer regimens. Our experience with this drug as well as at other institutions in individual patients demonstrates a possible benefit in decreasing some of the side effects from AZD-2171. At our institution , we have had four patients who have tried this combination and may have tolerated the AZD2171 better.  
STUDY NUMBER: 07-C-0059 CONTINUATION: page 3 of 12 pages
Clinical trial: NCT00436956
Section: Purpose of Research
Subsections: Description Of Research Study Why Is This Study Being Done?

The purpose of this study is to determine what effects, good and/or bad AZD2171, an unproven anticancer drug, has on you and your prostate cancer. This study will also help to determine how AZD2171 works in patients who have prostate cancer. AZD2171 is an experimental drug, not yet approved by the Food and Drug Administration. This study is being done in collaboration with Astra Zeneca, the makers of AZD2171, in an effort to understand the utility of this drug. The drug is an oral inhibitor of angiogenesis, the process of creating new blood vessels. All solid tumors require new blood vessels to grow. We hope to inhibit tumor growth with AZD2171 by preventing the growth of new blood vessels.
Clinical trial: NCT00436956
Section: Voluntary Participation
Subsections: Making Your Choice

Please read each sentence below and think about your choice. After reading each sentence, circle "Yes" or "No". If you have any questions, please talk to your doctor or nurse, or call the NIH Clinical Center Patient Representative at (301) 496-2626. No matter what you decide to do, it will not affect your care. 1. My tissue may be kept for use in research to learn about, prevent, or treat cancer.  
Yes No 2. My tissue may be kept for use in research to learn about, prevent or treat other health problems (for example: diabetes, Alzheimer's disease, or heart disease).  
Yes No  
  
3. Someone may contact me in the future to ask me to take part in more research.  
Yes No  
  
Where can I get more information? You may call the National Cancer Institute's Cancer Information Service at:
1-800-4-CANCER (1-800-422-6237) or TTY: 1-800-332-8615 You may also visit the NCI Web site at http://cancer.gov/
- For NCI's clinical trials information, go to: http://cancer.gov/clinicaltrials/ - For NCI's general information about cancer, go to http://cancer.gov/cancerinfo/
You will get a copy of this form. If you want more information about this study, ask your study doctor.
Clinical trial: NCT00436956
Section: Withdrawal from Study
Subsections: Can I Stop Being In The Study?

Yes. You can decide to stop at any time. Tell your study team if you are thinking about stopping or decide to stop. He or she will tell you how to stop safely. It is important to tell your study team if you are thinking about stopping so any risks from AZD2171 can be evaluated by your study team. Another reason to tell your study team that you are thinking about stopping is to discuss what follow-up care and testing could be most helpful for you. Your study team may stop you from taking part in this study at any time if they believe it is in your best interest, if you do not follow the study rules, or if the study is stopped.