Clinical trial: NCT04237584
Section: Alternatives
Subsections: Alternatives To Participation

You do not have to be in this study to receive treatment for your mCRPC. Your options may include:
Your physician may order Xtandi as well as Xofigo which are routine drugs to give for patients whose cancer has spread. There might be other drugs that your physician can discuss with you, including the risks and benefits of their use.  
If you decide that you don't want any more active treatment, one of your options is called "comfort care", also called palliative care. This type of care helps reduce pain, tiredness, appetite problems and other problems caused by the 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. If you think you might prefer comfort care, please discuss this with your family, friends and your doctor.
Your participation in this study is voluntary. Please talk to the study doctor about your options before you decide whether or not you will take part in this study. NEW FINDINGS Any new important information that is discovered during the study and which may influence your willingness to continue participation in the study will be provided to you.
Clinical trial: NCT04237584
Section: Confidentiality
Subsections: What Happens To The Information Collected For This Research?|Staff. Confidentiality

Efforts will be made to keep your records private to the degree allowed by law. Research records are stored and kept according to legal requirements. You will not be identified in any reports or publications about this study. No one can promise complete secrecy. Your records may be reviewed by the following groups:
The IRB (Institutional Review Board) committee that oversees the research; The sponsor of the study, their agents or study monitors; U.S. Food and Drug Administration; Your insurance company; Members of the study staff; Additional groups explained in the HIPAA Authorization for Research.  
If you consent to the additional blood draw for future prostate cancer research those samples will be deidentified (no name or medical record number) and may be used by others without seeking additional consent from you. There is a risk of potential loss of confidentiality. Every effort will be made to keep your information confidential; however, this cannot be guaranteed. You may stop your participation in this study at any time. A non-medical risk is the disclosure of your protected health information (PHI). PHI is any health information that is collected about you, including your history and new information collected during this study. If your study involves the use of your medical records, you will have an opportunity to review the ways in which your PHI may be used and disclosed in the HIPAA Authorization for Research part of this consent. 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. If you decide to take part in this research study, you will have tests, exams and procedures that are part of your usual care and you will have additional ones for study purposes. There are 3 drugs that are being studied in this research. Xtandi, Nubeqa and Xofigo. You will take by mouth either Xtandi or Nubeqa for 12-16 weeks. Then you will have either Xofigo or placebo (saline) injected into your veins monthly for 6 months while you continue taking either Xtandi or Nubeqa. Whether you take Xtandi or Nubeqa or receive Xofigo or placebo will be decided by randomizations (flip of a coin) performed by a computer.

Records of your participation in this study will be held confidential except when sharing the information is required by law or as described in this informed consent. The Investigator, the sponsor or persons working on behalf of the sponsor, and under certain circumstances, the United States Food and Drug Administration (FDA) and the Institutional Review Board (IRB) will be able to inspect and copy confidential study-related records which identify you by name. This means that absolute confidentiality cannot be guaranteed. If the results of this study are published or presented at meetings, you will not be identified. 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: NCT04237584
Section: Duration of Study Involvement
Subsections: How Long Will You Be In This Research?

It may take up to 42 days to be accepted into the study during the screening process. Upon entry into the study, there are three (3) phases: Phase 1 will be 12-16 weeks of an oral (by mouth) therapy. In this phase you will take only Xtandi or Nubeqa with your androgen deprivation therapy (ADT) and a bone health agent. Phase 2 will take up to 6 months and will include the addition of 1-6 monthly injections with Xofigo (a form of radiation therapy) or placebo along with Xtandi or Nubeqa. Phase 3 will be follow-up which can last about 3-4 years on average. In total you can expect to be in the study for up to 4 years.
Clinical trial: NCT04237584
Section: Participant Responsibilities
Subsections: Expectations

If you participate in this study, you will be expected to:
Attend study visits to complete the visit expectations Complete iPAD tests and questionnaires Take study medications per Investigator's instruction. Bring partial and full medication bottles to visits for verification you are taking medications.
Clinical trial: NCT04237584
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: What Impact Will Participating In This Research Have On You? Will Your Participation Reduce Your Options For Standard Treatments? It Is Not Yet Known Exactly How Your Participation In This Study Will Impact Your Future Treatment Options. How Will Your Experience In This Study Differ From Treatment Outside Of The Study|Could Being In This Research Hurt You?|Risks, Side Effects, And/Or Discomforts Risks Of Xtandi|Risks Of Nubeqa|Risks Of Study Procedures|Allergic Reaction Risks|Unforeseen Risks|Birth Control Restrictions

There will be a few tests that may not normally done such as:
Questions about how often you take Xtandi or Nubeqa A few tests, similar to games, using an iPAD to measure your cognitive function (brain function) A walking test ECG (to measure the electrical activity of your heart) Two questionnaires answered on an iPAD: one to see how you feel and another to see how well your brain is working Your doctor visits will take extra time due to these extra tests.

While on the study, you are at risk for the following side effects. Most of them are listed below but they will vary from person to person

Xtandi likely side effects (seen in greater than 50% of patients):
Increased blood sugar Feeling tired or weak Xtandi frequent side effects (seen in 1-50% of patients):
Back pain Hot flush Constipation Diarrhea Joint pain Blood counts decreased Decreased appetite Muscle pain Upper/lower respiratory infection Changes in blood chemistry Swelling of the face, arms, hands, lower legs, or feet Increase in blood pressure Nausea Falls Headache Dizziness Weight loss or lack or hunger Troubled breathing with exertion Muscle weakness Fractures Not able to sleep Blood in the urine Changes in taste Spinal cord compression Tingling of the hands or feet Anxiety Confusion or memory problems Frequent urination Decreased sensation (skin) Itching Dry skin Enlarged breast tissue (males) Nosebleed Muscle stiffness Restless legs Xtandi rare side effects (seen in less than 1% of patients):
Seizures

Nubeqa frequent side effects (seen in 1-50% of patients):
Feeling tired or weak Back pain Joint pain Arm, leg, hand, or foot pain Nausea Constipation Diarrhea Decreased appetite Muscle pain Vomiting Anemia (decreased red blood cells) Headache Difficulty with sleep Weight decreased Swelling in hands, arms, legs and feet Blood in urine Bone pain Hot flashes High blood pressure Troubled breathing with exertion Fall Common cold Prostate cancer Rash Changes in blood (lab) results General health decline Acute kidney injury Gas Enlarged breasts in males Abdominal bloating Changes in taste Slow elimination Infection Frequent urination Kidney infection Difficulty with urination Urinary tract infection Nubeqa rare side effects (seen in less than 1% of patients):
Pneumonia Risks of Xofigo Xofigo likely side effects (seen in greater than 50% of patients):
Bone pain Xofigo frequent side effects (seen in 1-50% of patients):
Nausea Weight decreased Feeling tired or weak Diarrhea Dehydration Redness, pain or swelling at injection site Low blood cell counts Vomiting Constipation Progression of cancer Swelling in arms or legs (extremities) Urinary tract infection Troubled breathing with exertion Dizziness Fever Decreased appetite General health decline Difficulty with sleeping Difficulty with urination Blood in urine Headache Fracture Spinal cord compression Pneumonia Tingling sensation in skin Common cold Frequent urination Confusion Rectal bleeding Kidney failure and impairment Xofigo rare side effects (seen in less than1% of patients):
Joint swelling There also may be other side effects or discomforts that we cannot predict, especially to a fetus or embryo. Because the drugs in this study may affect an unborn baby, you should not father a baby while on this study. Your study doctor will discuss this with you.

Blood samples: Possible side effects from blood drawing include faintness, inflammation of the vein, pain, bruising, or bleeding at the site of puncture. There is also a slight possibility of infection.  
Electrocardiogram (ECG): Skin irritation is rare but could occur during an ECG from the electrodes or gel that is used.  
Questionnaires: The questionnaires used in this study may be upsetting. You do not need to answer any questions that you are not comfortable with.  
Despite getting study treatments, your symptoms of mCRPC may not improve or may get worse.

As with taking any drug, there is a risk of allergic reaction. If you have a very serious allergic reaction, you may be at risk of death. Some symptoms of allergic reactions are:
Rash Wheezing and difficulty breathing Dizziness and fainting Swelling around the mouth, throat or eyes A fast pulse Sweating Please seek treatment immediately and tell the study doctor and study staff if you have any of these symptoms.

Since the use of the Nubeqa for mCRPC is investigational, there may be other risks that are unknown. Additionally, there may be unknown risks to a pregnancy, embryo, or fetus if your female partner become pregnant.

In order to reduce the risk of pregnancy, you should use an effective method of birth control while you are participating in this study and for 6 months after your last dose of the study drug. Acceptable methods of birth control for use in this study are condoms plus spermicidal agent. The Investigator or study staff will discuss this with you. If your female partner becomes pregnant while you are participating in this study or within 6 months after you have stopped taking the study drug, tell your Investigator or study staff immediately.
Clinical trial: NCT04237584
Section: Procedures
Subsections: Screening:|Study Treatment - Phase 1|Phase 1 Psa Visits, 3 Visits:|Evaluation For Second Study Treatment Phase Of The Study:|Study Treatment - Phase 2|Xofigo Or Placebo Injection Visits:|Clinic Visits Before 2Nd- 6Th Injection Visits:|Imaging Visits While Taking Xofigo:|Follow-Up– Phase 3|End Of Follow-Up:|After Study Treatment:

Before any study-related tests and procedures are performed, you will be asked to read and sign this consent document. If you have had some of these tests or procedures within 42 days of starting the study drug, they may or may not have to be repeated. The screening tests and procedures listed below are performed to  
determine if you qualify to take part in this study. If the review of your medical history and/or medications show you do not qualify for the study, you might not need to do all the screening tests.:
Lab work to make sure you can take either Xtandi or Nubeqa (about 2 tablespoons)
ECG: a test that measures the electrical activity of the heartbeat.  
MRI or CT and bone scans images to see bone and tissue structures inside your body. Review of your medical history including your risk for future bone fractures. Review of your use of bone health agents and your past prostate cancer treatments. Collection of information about you including race, ethnicity, and highest level of education. Review of medications you are currently taking and recently stopped medications. A physical examination including measurement of your height, weight, vital signs, and current health status Using an iPAD, you will do practice tests to get you familiar with the real tests that will be done later in the study Collect a blood sample (about 2 teaspoons) for future prostate cancer research (this is optional) and you can decline to participate on the signature page of this document Obtain a prescription for enzalutamide and start the process for insurance coverage.
Screening can be completed in multiple visits, if needed. The total time should take about 2 hours. After screening, but before your first dose of Xtandi or Nubeqa:  
Using an iPad you will complete two (2) questionnaires to measure your cognitive (brain) status and the way you are feeling (well-being). An iPAD will also be used to take a series of four (4) tests to further measure your cognitive (brain) function You will have a walking test to see how fast you can safely get up from a chair and walk 10 feet, turn around and return to your chair
If you are eligible (fit all entry criteria) you will be randomized (flip of a coin) by a computer to one of the two androgen blocking drugs Xtandi or Nubeqa. This visit should take about one hour to complete. This study will use competitive enrollment. This means that when a target number of subjects begins the study, all further enrollment will be closed. Therefore, it is possible that you could be in the screening phase, ready to begin the study, and be discontinued without your consent if the target number of subjects has already begun the study. If you qualify to take part in this study and go on to receive the study treatment, then the following will happen:

For your first study treatment phase, you will be randomly assigned by chance (like the flip of a coin) to receive either Xtandi or Nubeqa. You will have a 50% (1 in 2) chance of receiving Xtandi and a 50% (1 in 2) chance of receiving Nubeqa. This part of the study is open-label. This means that you, the Investigator, study staff and the Sponsor will know the study drugs and the doses that you are given.  
If you are assigned to Xtandi, you will need to get your prescription filled, start taking the study medication according to the Investigator's instruction, and notify your Investigator when you have started the drug.
If you are assigned to Nubeqa, you will get your first bottle of study medication at this visit and can start taking the medication according to the Investigator's instruction.  
You will continue to take your current hormone therapy as well as a bone protective drug which your study doctor has already ordered for you as routine therapy.  
You will have the following study visits and undergo the following procedures:

You will need to take the study medication assigned to you by the first randomization. Xtandi is usually given (4 capsules) once daily and Nubeqa is usually given (2 tablets) twice daily. During the visits, the following will be done:
PSA blood levels checked Review how you are feeling, doctor visits or hospitalizations that have occurred Review and dispense study medications, when needed The PSA test is routinely done for all patients regardless of whether they are or are not participating in a study while receiving these drugs. These monthly visits should take about ½ hour to complete. Your scans will be scheduled every 12-weeks, which is also routine while taking these drugs. This visit may take approximately one hour to complete

After taking either Xtandi or Nubeqa for at least 12 weeks you and your study doctor will decide if you can go onto the second study treatment phase. In order to make the decision your study doctor will need to:
Repeat the same scans you had when you entered the study (CT or MRI and bone scan) Repeat lab work (about 2 tablespoons) will be used to help determine if it is safe for you to move to the second study treatment phase.  
Repeat ECG A short physical examination, vital signs, and determination of your current health status. Review all medications you are taking Using an iPad you will complete two (2) questionnaires to measure your cognitive (brain) status and the way you are feeling (well-being). An iPAD will also be used to take a series of four (4) tests to further measure your cognitive (brain) function Walking test Collect a blood sample (about 2 teaspoons) for future prostate cancer research if you consented to this Review how you are feeling, doctor visits or hospitalizations that have occurred Review of your study medications and dispensing more study medication, if needed If you are eligible (fit all entry criteria) for the second study treatment phase, you will be randomized (flip of a coin) by a computer to either Xofigo or placebo. If the decision is made not to proceed to the second randomization, your study doctor will discuss other treatment options with you and your participation in the study will end after collection of End of Study information.

For your second study treatment phase, you will be randomly assigned by chance (like the flip of a coin) to receive either Xofigo (radium-223) or placebo (inactive substance). You will have a 50% (1 in 2) chance of Xofigo (radium-223) and a 50% (1 in 2) chance of receiving placebo. This second random assignment is a double-blind, which means neither you nor the Investigator will know to which of these study drug groups you are assigned. In case of an emergency, however, the Investigator can get this information. Xofigo is FDA approved for men whose cancer has spread to bones. Xofigo will be supplied to you by the study at no cost to you or your insurance company.

For this second phase of the research you will be taking all the same medications you have been taking for the past 12-16 weeks and you will have monthly injections of Xofigo or placebo until 6 doses have been given. Xofigo or placebo will be administered in a radiation therapy clinic. The research staff will schedule your injections for you and will tell you where the clinic is located. It should take less than a ½ hour for these visits.

You will return to the clinic every month after your first Xofigo or placebo dose to have routine blood work done to monitor you for safety and review your medications in order to make sure it is still safe for you to receive the next month's injection. These visits should take about ½ hour.  
The clinic visits between injection visits will include:
Vital signs and determination of your current health status Review how you are feeling, doctor visits or hospitalizations that have occurred Review all medications you are taking Review of your study medications and dispensing more study medication, if needed

Every 3 months starting from the date of your first injection of Xofigo or placebo you will have the same imaging tests (CT/MRI/bone scan) you had before, an abbreviated physical exam, and the site staff will ask you questions about how you are feeling and about any doctor visits or hospitalizations that have occurred since your last visit. These are routine for patients with prostate cancer undergoing these therapies. The scans should take approximately one hour.

After you have completed or stopped the Xofigo/placebo injections and your study doctor has determined that your disease has or has not progressed based on your imaging results and your clinical findings, your study doctor will make a decision about your next treatment option. This may include continuing Xtandi or Nubeqa or possibly starting you on a new treatment. If you continue Nubeqa, it will be supplied to you by the study.  
If you continue taking Xtandi or Nubeqa you will visit the clinic every 12 weeks for:
Repeat the same scans you had when you entered the study (CT or MRI and bone scan) Repeat of your blood work Vital signs Review all medications you are taking Review how you are feeling, doctor visits or hospitalizations that have occurred Review of your study medications and dispensing more study medication, if needed Once every 48 weeks: Repeat ECG, determination of your current health status, and walking test
Follow up visits will be done until either your disease progresses, or your study doctor decides to start a therapy that is not allowed on this research study. These visits should take about an hour.

If you or your study doctor decides to stop your Xtandi or Nubeqa due to progression of your mCRPC or in order to start a new therapy that is not allowed on the study, you will be asked to return to the clinic for:
Return of study medication(s), if applicable Review how you are feeling, doctor visits or hospitalizations that have occurred Review all medications you are taking Review of your study medications Collect a blood sample (about 2 teaspoons) for future prostate cancer research if you consented to and if your disease has progressed This visit will take about 1 hour.

Because this is a research study, the study drug will be given to you only during this study and not after the study is over. We will contact you every 6 months to see how you are doing. This can be done with a phone call or a review of your medical record. In the event we cannot reach you, we will perform a public records search until the study ends for all subjects.
Clinical trial: NCT04237584
Section: Purpose of Research
Subsections: What Is The Research Question The Study Is Trying To Answer?|In What Ways Is This Research New?|Benefits

The research is designed to answer whether adding monthly Xofigo injection following 12-16 weeks of oral Xtandi or Nubeqa improves your prostate cancer outcome. The best time to add monthly injections of Xofigo after 12-16 weeks of Xtandi or Nubeqa has not been established. This study will add Xofigo after you have taken Xtandi or Nubeqa for 12-16 weeks, rather than giving Xofigo at the same time as Xtandi or Nubeqa. This will allow researchers to evaluate if this dosing schedule will prevent or delay the negative consequences of cancer which has spread to bone such as bone pain, fractures, and spinal cord compression (an area of cancer that presses on the spinal cord). More information on all drugs used in this study are explained later in this document. About 599 subjects will take part in this research.

In this study, if you are on the study drug (Xofigo), you will receive it earlier than you would typically receive it if you were not on this study. It is more common to receive Xofigo only after further prostate cancer progression has occurred. If you are on the placebo (saltwater), your study treatment will be closer to what occurs in most clinical practices.

You may benefit as a result of your participation in this study. There is, however, no guarantee that you will benefit from your participation in this study. Information learned from the study may help other people in the future.
Clinical trial: NCT04237584
Section: Voluntary Participation
Subsections: Voluntary Participation / Withdrawal|Consent Statement

Your decision to participate in this study is voluntary. You may choose to not participate or you may withdraw from the study for any reason without penalty or loss of benefits to which you are otherwise entitled and without any effect on your future medical care. However, please note that the FDA requires that any information collected up to the point of your withdrawal cannot be removed from the study. If you or your study doctor decides to stop your participation, you will be asked to return to the clinic for:
Return of study medication(s), if applicable Review how you are feeling, doctor visits or hospitalizations that have occurred Review all medications you are taking Review of your study medications This visit should take about an hour. The Investigator or the sponsor can stop your participation at any time without your consent for the following reasons:
If it appears to be medically harmful to you; If you fail to follow directions for participating in the study; If it is discovered that you do not meet the study requirements; If the study is canceled; or For administrative reasons.  
If you leave the study for any reason, the Investigator may ask you to have some end-of-study tests for your safety.

I have read and understand the information in this informed consent document. I have had an opportunity to ask questions and all of my questions have been answered to my satisfaction. I voluntarily agree to participate in this study until I decide otherwise. I do not give up any of my legal rights by signing this consent document. I will receive a copy of this signed and dated consent document. ________________________________________  
 Subject's Printed Name  
________________________________________ ___________  
  
Subject's Signature Date ________________________________________  
   
________________________________________ ___________  
  
 Signature of the Person Conducting the Date Consent Discussion