Clinical trial: NCT02064582
Section: Alternatives
Subsections: What Options Are Available If I Decide Not To Take Part In This Research Study?

You do not have to participate in this research to receive care for your medical problem. Instead of being in this study, you have other options. Standard of care treatment may include, depending on evidence of pelvic nodal involvement and your overall clinical status, androgen deprivation therapy combined with radiation therapy OR in some cases a radical prostatectomy. Taking part in another study may also be an option. You may also elect not to receive any treatment after discussing with your personal physician about these options.  
Please talk to the researchers or your personal doctor about these options.
Clinical trial: NCT02064582
Section: Confidentiality
Subsections: Will My Information Be Kept Confidential?

Medical information collected during this study and the results of any test or procedure that may affect your medical care may be included in your medical record. The information included in your medical record will be available to health care providers and authorized persons including your insurance company. You should know that certain organizations that may look at and/or copy your medical records for research, quality assurance, and data analysis include:
- Astellas Pharma - Representatives of government agencies, like the U.S. Food and Drug 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. In addition to this consent form, you will be asked to sign an "Authorization for Use and Disclosure of Protected Health Information." This authorization will give more details about how your information will be used for this research study, and who may see and/or get copies of your information.  
Are there procedures I should follow after stopping participation in this research?  
Yes. If you, the researchers, or the sponsor stops your participation in the research, you may be asked to do the following:  
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Administration (FDA), involved in keeping research safe for people; and
- The UT Southwestern Institutional Review Board.  
Let the researchers know immediately that you wish to withdraw from the research.  
Return to the research center for tests that may be needed for your safety.  
Return any unused study materials, including empty containers.  
Discuss your future medical care, if any, with the researchers and/or your personal doctor.
Clinical trial: NCT02064582
Section: Duration of Study Involvement
Subsections: How Long Can I Expect To Be In This Study?

You participation in this study may last up to 36 months. You can choose to stop participating for any reason at any time. However, if you decide to stop participating in the study, we encourage you to tell the researchers. You may be asked if you are willing to complete some study termination tests.
Clinical trial: NCT02064582
Section: Participant Responsibilities
Subsections: What Should I Do If I Think I Am Having Problems?

If you have unusual symptoms, pain, or any other problems while you are in the study, you should report them to the researchers right away. Telephone numbers where they can be reached are listed on the first page of this consent form. If you have a sudden, serious problem, like difficulty breathing or severe pain, go to the nearest hospital emergency room, or call 911 (or the correct emergency telephone number in your area). Tell emergency personnel about any medications you are taking, including any medications you are taking for this study.
Clinical trial: NCT02064582
Section: Participant's Rights
Subsections: If I Agree To Take Part In This Research Study, Will I Be Told Of Any New Risks That May Be Found During The Course Of The Study?

Yes. You will be told if any new information becomes available during the study that could cause you to change your mind about continuing to participate or that is important to your health or safety.
Clinical trial: NCT02064582
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: What Are The Risks Of The Study? Study Procedure/Intervention|Psychological Stress|Loss Of Confidentiality|Risks To Sperm, Embryo, Fetus Or Breast-Fed Infant|Risks Of Radiation - Diagnostic Test|Risks Of Radiation - Radiation Therapy|Risks Of Blood Drawing|What Are The Possible Benefits Of This Study?

Because of your participation in this study, you are at risk for the following side effects. You should discuss these with the researchers and your regular health care provider. Enzalutamide (MDV3100) may cause some, all or none of the side-effects listed below. You may experience side effects while on 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. Side effects may be mild or very serious. Your health care team may give you drugs to help lessen side effects. Side effects may go away soon after you stop taking study drug. In some cases, side effects can be serious, long lasting, or may never go away. You should talk to your study doctor about any side effects that you may have while taking part in the study. In the Phase 3 study CRPC2, 800 patients were treated with enzalutamide (MDV3100)at a dose of 160 mg daily and 399 patients were treated with placebo (a substance that does not contain any active drug). Side effects reported in at least 5% of enzalutamide (MDV3100)-treated patients and at a rate that was at least 2% higher than in placebo-treated patients included fatigue, diarrhea, hot flush, pain in muscles and bones, headache, trouble sleeping, anxiety, high blood pressure, and cold symptoms (congested nose and sore throat). Other side effects reported in less than 5% of enzalutamide (MDV3100)-treated patients and at a higher rate than placebo-treated patients included falls, dry skin, itchiness, thinking or memory problems, and hallucinations (seeing or feeling things that are not there). Seizures (such as convulsions) have been infrequently reported in patients (less than 1% of patients) receiving enzalutamide (MDV3100) and not in placebo-treated patients. Due to this potential risk of seizure, please inform your study doctor if you have ever had a condition that may increase the risk of seizures, such as prior history of seizure, brain injury, or brain tumor; stroke; or history of alcoholism. There are some medicines that are known to increase the chance of having a seizure. These medicines include but are not limited to:
- Aminophylline/theophylline
- Atypical antipsychotics (e.g., clozapine, olanzapine, risperidone, ziprasidone)
- Bupropion
- Lithium
- Meperidine (Demerol) - Phenothiazine antipsychotics (e.g., chlorpromazine, mesoridazine, ,
prochlorperazine, thioridazine)
- Tricyclic and tetracyclic antidepressants (e.g., amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine)
These medicines may increase your risk of developing seizures when used with enzalutimide (MDV3100). It is important for you to tell your study doctor all of the medicines you are taking. There have been rare reports of posterior reversible encephalopathy syndrome (PRES), a rare, reversible condition involving the brain, in patients treated with enzalutamide. If you have a seizure, worsening headache, confusion, blindness or other vision problems, please contact your doctor right away. Your doctor will stop enzalutamide if you develop PRES. In addition, some medicines may affect how enzalutamide (MDV3100) is broken down by your body. Caution should be used when taking certain medicines or substances because they may increase the amount of enzalutamide (MDV3100) in your blood. These include but are not limited to clarithromycin, gemfibrozil, grapefruit, itraconazole, and ketoconazole. Also, caution should be used when taking certain medicines or substances because they may lower the amount of enzalutamide (MDV3100) in your blood. These include but are not limited to carbamazepine, phenytoin, rifampin, and St. John's wort. Because enzalutamide (MDV3100) blocks the action of the male sex hormone, it is expected to cause infertility and impotence and may contribute to loss of muscle and bone, hot flashes or breast growth. Because you can only be in this study if you are taking other drugs that decrease male sex hormones or have had a bilateral orchiectomy, you may or may not notice additional changes related to decreased male sex hormone action after receiving enzalutamide (MDV3100). Even though the risk of getting your partner pregnant while taking enzalutamide (MDV3100) is low, to participate in this study you must agree to utilize effective birth control methods to ensure that your partner does not become pregnant. Most men participating in this study may experience long term impotence due to the overall treatment for their prostate cancer. Possible risk and side effects related to the *GnRH*: Most Common **(30% or more)** - Hot flashes - Erectile Dysfunction - Feeling tired - Nausea Very Common (10% or more to **less than 30%)**
- Constipation - Headache - Loss of appetite - Diarrhea - Dizziness - Skin rash, covering part or most of body - Joint pain - Increase in a type of fat in blood - Difficulty breathing during physical activity - Changes in electrocardiogram (QTc, length) - Hot flush - Bone or liver enzyme increased in blood - High blood sugar (glucose) - Dizziness - Protein in urine - Change in sense of taste - High blood pressure - Low white blood cells Patients receiving treatment with LHRH agonists should undergo periodic monitoring of blood glucose and/or glycosylated hemoglobin (HbA1c) for signs of developing diabetes or worsening of blood glucose control in patients with diabetes, and also for the signs and symptoms suggestive of the development of cardiovascular disease.

Some of the questions we will ask you as part of this study may make you feel uncomfortable. You may refuse to answer any of the questions, take a break or stop your participation in this study at any time.

Any time information is collected; there is a potential risk for loss of confidentiality. Every effort will be made to keep your information confidential; however, this cannot be guaranteed.

Males: Being in this research may damage your sperm, which could cause harm to a child that you may father while on this study. If you take part in this study and are sexually active, you must agree to use a medically-acceptable form of birth control. Medically-acceptable forms of birth control include:
(1) surgical sterilization (vasectomy), or (2) a condom used with a spermicide (a substance that kills sperm). ______I agree to use medically acceptable birth control for 90 days after stopping Enzalutamide ______ I do not agree to use medically acceptable birth control for 90 days after stopping Enzalutamide

The radiation dose that you will get from diagnostic tests is medically indicated for your condition and it is the same that you would get if you were not involved in this research study.

The radiation therapy used in this research is the standard radiation therapy for your health problem; therefore, the risk of harm to your body is the same. Your radiation doctor will discuss the known risks of radiation therapy with you and ask you to sign a separate specific treatment site consent form. High-dose radiation treatments to or near a man's testicles may produce harmful changes that could be passed on to children through a sperm. You must avoid fathering a child until ten weeks after the end of all radiation therapy. After that period, there is much less risk of harmful changes to sperm. Even then there is still an unknown amount of risk. Possible side effects of radiation therapy to the prostate include: Short Term effects: Inflammation of the bowel causing cramping and diarrhea; inflammation of the rectum and anus causing pain, spasm, discharge, bleeding; bladder inflammation causing burning, frequency, spasm, pain, and/or bleeding; skin changes: redness, irritation, scaliness, blistering or ulceration, coloration, thickening, hair loss; depression of blood counts leading to increased risk of infection and/or bleeding. Long Term effects: bowel damage causing narrowing or adhesions of the bowel with obstruction, ulceration, bleeding, chronic diarrhea, or poor absorption of food elements and may require surgical correction or colostomy; bladder damage with loss of capacity, frequency of urination, blood in urine, recurrent urinary tract infections, pain, or spasm which may require urinary diversion and/or removal of the bladder; changes in skin texture and/or coloration, permanent hair loss, and scarring of skin; bone damager leading to fractures; testicular damage causing reduced sperm counts, infertility, sterility, or risk of birth defects; impotence (loss of erection) or sexual dysfunction; swelling of the genitalia or legs; nerve damage causing pain, loss of strength or feeling in legs, and/or loss of control of bladder or rectum; fistula between the bowel and other organs. Prostate Ultrasound and Biopsy: The transrectal ultrasound may be associated with discomfort and very rarely, rectal bleeding. A transrectal ultrasound involves inserting a probe into the rectum. The machine visualizes (allows the doctor to see) the rectum and prostate by sending high frequency sound waves (signals) from the probe and measuring the waves as they are reflected back, producing images on a screen. During the prostate biopsy procedure, up to twelve very small samples of tissue are withdrawn from the prostate through a needle. You may feel a stinging sensation each time a sample is taken, but usually any soreness or discomfort quickly passes. After the biopsy, you may experience minor bleeding in the urine or rectum, or blood-tinged ejaculate (the fluid released by the prostate during sexual intercourse). There are also small risks of temporary inability to urinate or infection. An antibiotic is prescribed by your doctor to prevent infection.

Risks associated with drawing blood from your arm include minimal discomfort and/or bruising. Infection, excess bleeding, clotting, and/or fainting also are possible, although unlikely. You will have 30 tablespoons of blood collected because you are in this research study. Other Risks There may possibly be other side effects that are unknown at this time. If you are concerned about other, unknown side effects, please discuss this with the researchers. How will risks be minimized or prevented? You will be monitored periodically during the study through study visits to make sure that you are doing well. If you have any problems, you can contact the study staff at the numbers on the front of this form.  
What will my responsibilities be during the study? While you are part of this study, the researchers will follow you closely to determine whether there are problems that need medical care. It is your responsibility to do the following:
Ask questions about anything you do not understand.  
Keep your appointments.  
Follow the researchers' instructions.  
Let the researchers know if your telephone number or address changes.  
Store study materials (tablets) in a secure place at home away from anyone who is unable to read and understand labels, especially children.  
Tell the researchers before you take any new medication, even if it is prescribed by another doctor for a different medical problem or something purchased over the counter.  
Tell your regular doctor about your participation in this study.  
Carry information about the research medication in your purse or wallet. Report to the researchers any injury or illnesses while you are on study even if you do not think it is related.

If you agree to take part in this study, there may or may not be direct benefits to you. The researchers cannot guarantee that you will benefit from participation in this research. We hope the information learned from this study will benefit others with high-risk localized or locally advanced prostate cancer in the future. Information gained from this research could lead to better treatment.
Clinical trial: NCT02064582
Section: Procedures
Subsections: What Is Involved In The Study?|Screening Procedures|Study Medication/Intervention|Procedures And Evaluations During The Research|Procedures For Storing Of Extra Or Left Over Samples

If you volunteer to take part in this research study, you will be asked to sign this consent form and will have the following tests and procedures. Some of the procedures may be part of your standard medical care, but others are being done solely for the purpose of this study.

To help decide if you qualify to be in this study, the researchers will ask you questions about your health, including medications you take and any surgical procedures you have had. The screening procedures could take from 30- 120 minutes to complete. The scans could be done on other days taking up to 2 hours to complete. You may also have to fill out certain forms or have the following exams, tests or procedures:
Medical History Demographic information Review both eligibility criteria and other medications that you take Physical exam including vital signs, height and weight Questionnaire completion Blood tests - approximately 2 tablespoons of blood will be collected CT of the abdomen and pelvis Bone scan Chest x-ray or CT of the chest Pelvic MRI Prostate biopsies performed as standard of care and additional samples for research purposes

You will receive treatment with enzalutamide by mouth plus Lupron ( the GnRH agonist) intramuscular ( into your muscle) for 8-10 weeks prior to starting your radiation therapy. During radiation therapy you will continue to receive the two medications for the duration of the radiation therapy. This will be approximately 8-10 weeks. Each radiation visit could last from 30-120 minutes.  
After you have completed your radiation therapy you will continue to receive the two medications until you have reached a total of 24 weeks duration of the two medications. After you have completed the 24 weeks of the two drug combination you will continue to receive GnRH agonist therapy until you have reached 24-36 months of total GnRH agonist treatment. The decision to continue GnRH agonist treatment for a total of 24 vs 36 months will be at the discretion of your treating physician.

One to two weeks prior to starting your treatment you will have a pelvic MRI and transrectal ultrasound (TRUS)-guided prostate biopsies. If you have not undergone previous prostate biopsies from which you have been diagnosed with high-risk prostate cancer, then both the standard diagnostic biopsies and research biopsies will be performed at the same time. If you have previously undergone prostate biopsies and been diagnosed with high-risk prostate cancer, you will undergo an additional TRUS-guided biopsy procedure to obtain prostate tissue for research purposes. This could take up to 2 hours to complete. Weeks 1-24 - prior to each cycle of enzalutamide and GnRH you will have the following tests done:
Physical exam including vital signs Blood work - approximately 2 tablespoons of blood will be taken from a vein in your arm This visit could take from 30 to 60 minutes.  
Week 8 - You will have magnetic resonance imaging (MRI) of your pelvis. For this procedure, you will lie quietly inside a large, doughnut-shaped magnet for about sixty minutes. You will also have fiducial marker (gold seed) placement and TRUSguided targeted prostate biopsies. *This visit could take up to 120minutes to complete.*
Every 4 weeks after you have started taking enzalutamide you will have a physical exam with vital signs and blood drawn. You will have approximately 2 tablespoons of blood drawn at each of these visits. These visits can last from 30- 60 minutes.  
| This table outlines your study visits: Pre-study  Days -56 to - 14 Day 1                                                          | Every 4  weeks  (weeks 4- 48)   | Week 8   | End of   |    |
|-----------------------------------------------------------------------------------------------------------------------------------|---------------------------------|----------|----------|----|
| study visit                                                                                                                       |                                 |          |          |    |
| Informed Consent                                                                                                                  | X                               |          |          |    |
| History and PE                                                                                                                    | X                               | X        | X        | X  |
| Performance                                                                                                                       | X                               | X        | X        | X  |
| Status Blood tests                                                                                                                | X                               | X*       | X        | X  |
| CT abd/pelvis Chest X-ray or                                                                                                      | X                               |          |          |    |
| CT chest Bone scan                                                                                                                | X                               |          |          |    |
| MRI pelvis                                                                                                                        | X                               | X        |          |    |
| TRUS-guided                                                                                                                       | X                               | X        |          |    |
| prostate biopsy *Blood tests will be repeated on day 1 if pre-screening blood work was done greater than  28 days prior to day 1. |                                 |          |          |    |  
The extra prostate biopsies and extra blood sample at the screening visit and two months on treatment in this study are designed for research, not for medical purposes. They are not useful for finding problems or diseases. Even though the researchers are not looking at your research prostate biopsies and extra blood sample to find or treat a medical problem, you will be told if they notice something unusual. You and your regular doctor can decide together whether to follow up with more tests or treatment. Because the prostate biopsies and extra blood test done in this study are not for medical purposes, the research results will not be sent to you or to your regular doctor. The biopsies can take up to 120 minutes.

Some of your blood and prostate samples may be stored for future research. These samples will have all identifying information removed including your name, date of birth, medical record number. They will be labeled with a code that only the study staff will have access to. These samples may be used for future research studies on prostate cancer or other diseases.
Clinical trial: NCT02064582
Section: Purpose of Research
Subsections: Why Is This Study Being Done?|Why Is This Considered Research?

The study is being done to find out whether combining the two FDA approved drugs enzalutamide (an androgen receptor blocker) and gonadotropin-releasing hormone agonist (GnRH agonist) along with radiation therapy for the treatment of prostate cancer is safe and well-tolerated. The combination of enzalutamide plus a GnRH agonist is a standard of care treatment option for patients with metastatic prostate cancer that no longer responds to treatment with a GnRH agonist alone. The combination of a GnRH agonist plus radiation therapy (with or without an older androgen receptor blocker drug) is a standard of care treatment option for patients with high-risk localized and locally advanced prostate cancer. The combination of all three (enzalutamide, GnRH agonist, and radiation therapy) has not been previously tested in patients with localized prostate  
Title of Research: Phase II study of enzalutamide (MDV3100) and  
gonadotropin-releasing hormone (GnRH) agonist before, during and after radiation therapy in treatment of patients with high-risk localized prostate cancer  
cancer. It is possible that combining all three may provide more effective treatment for patients with high-risk localized or locally advanced prostate cancer. At UTSW, we have decided to use Lupron® as the GnRH medication for the study purposes.

This is a research study because these two drugs and radiation therapy have not been combined. The researchers are interested in learning if this combination is safe and well-tolerated and possibly more effective in treating your condition/disorder.
Clinical trial: NCT02064582
Section: Voluntary Participation
Subsections: Consent To Participate In Research|Why Am I Being Asked To Take Part In This Research Study?|Do I Have To Take Part In This Research Study?|Signatures: You Will Be Given A Copy Of This Consent Form To Keep.

Funding Agency/Sponsor: Sponsor- UTSouthwestern Medical Center  
Funding agency- Astellas Scientific and Medical Affairs, Inc.  
Study Doctors: Kevin Courtney, MD, PhD, Yull Arriaga, MD, Raquibul  
Hannan, MD, PhD, Michael Folkert, MD, Aaron Laine, MD, Neil Desai, MD  
You may call these study doctors or research personnel during regular office hours at 214-645-8787. At other times, you may call them at 214-645-4673.

You are being asked to take part in this study because you have been diagnosed with high-risk localized or locally-advanced prostate cancer, OR you have physical examination findings (an abnormal prostate on a digital rectal examination) and findings from blood work (elevation in your PSA) that are concerning for the possibility that you may have high-risk localized or locally-advanced prostate cancer and warrant further evaluation by prostate biopsy.

No. You have the right to choose whether you want to take part in this research study. If you decide to participate and later change your mind, you are free to stop participation at any time. If you decide not to take part in this research study it will not change your legal rights or the quality of health care that you receive at this center. How many people will take part in this study? About 15 people will take part in this study at UT Southwestern.

Your signature below certifies the following:  
You have read (or been read) the information provided above.  
You have received answers to all of your questions and have been told who to call if you have any more questions.
You have freely decided to participate in this research. You understand that you are not giving up any of your legal rights. You understand that a copy of this signed consent document, information about this study, and the results of any test or procedure that may affect your medical care, may be included in your medical record. Information in your medical record will be available to health care providers and authorized persons including your insurance company.  
____________________________________________ Name of Participant (Printed)  
____________________________________________ ________ _______ AM / PM  
  ____________________________________________  
  
 Name of Person Obtaining Consent (Printed) ____________________________________________ ________ _______ AM / PM  
 Signature of Person Obtaining Consent Date Time
Interpreter Statement: I have interpreted this consent form into a language understandable to the participant and the participant has agreed to participate as indicated by their signature on the associated short form.  
____________________________________________ Name of Interpreter (Printed) ____________________________________________ ________ _______ AM / PM  
  
 Signature of Interpreter Date Time
Clinical trial: NCT02064582
Section: Withdrawal from Study
Subsections: Can I Stop Taking Part In This Research Study?

Yes. If you decide to participate and later change your mind, you are free to stop taking part in the research study at any time. If you decide to stop taking part in this research study, it will not affect your relationship with the UT Southwestern staff or doctors. Whether you participate or not will have no effect on your legal rights or the quality of your health care. If you are a medical student, fellow, faculty, or staff at the Medical Center, your status will not be affected in any way. Your doctor is a research investigator in this study. He is interested in both your medical care and the conduct of this research study. At any time, you may discuss your care with another doctor who is not part of this research study. You do not have to take part in any research study offered by your doctor.  
If I agree to take part in this research study, can I be removed from the study without my consent? Yes. The researchers may decide to take you off this study if:
Your medical problem remains unchanged or becomes worse.  
The researchers believe that participation in the research is no longer safe for you.  
The researchers believe that other treatment may be more helpful.  
The sponsor or the FDA stops the research for the safety of the participants.  
The sponsor cancels the research.  
You are unable to keep appointments or to follow the researcher's instructions.