Clinical trial: NCT02504892
Section: Alternatives
Subsections: Alternative Approaches Or Treatments What Other Choices Do I Have If I Do Not Take Part In This Study?

Instead of being in this study, you have these options:
- Getting treatment or care for your cancer without being in a study  
- Taking part in another study
- Getting 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. Instead, it tries to improve how you feel. Comfort care tries to keep you as active and comfortable as possible.  
Please talk to your doctor about these and other options.  
| PATIENT IDENTIFICATION   | CONTINUATION SHEET for either: NIH-2514-1 (07-09) NIH-2514-2 (10-84) P.A.: 09-25-0099 File in Section 4: Protocol Consent   |
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Clinical trial: NCT02504892
Section: Confidentiality
Subsections: 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. 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.  
- Governmental agencies in other countries where the study drug may be considered for approval.  
- National Cancer Institute Institutional Review Board. - Qualified representatives from Novartis, the pharmaceutical company who produces everolimus.
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.  
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**  
NIH-2514-1 (07-09)  
NIH-2514-2 (10-84)  
P.A.: 09-25-0099  
File in Section 4: Protocol Consent
Clinical trial: NCT02504892
Section: Duration of Study Involvement
Subsections: During The Study

If you join this study, you will be given tablets to be taken by mouth. It is very important for you to take the study drug just as the study doctor tells you. Do not skip any doses unless your study doctor tells you to skip doses. If you throw up after taking the study drug, you should NOT take another tablet that day. Let your study doctor know that you got sick. If you do forget to take the study drug one day, do not take any extra doses the next day. Call your study doctor and ask for advice.  
You will be asked to take one tablet once a day. You will take everolimus for up to 52 weeks.  
You should take everolimus about the same time each day, either consistently with or without food. You should only take the study medicine as the doctor tells you to, and should not do anything else with it. During the study, you must talk to the study doctor before you take any drug other than the study drug. This includes homeopathic, alternative, or herbal medicines, and vitamins or other overthe-counter medications. Please avoid eating grapefruit, star fruit, and Seville oranges or drinking their juices while in the study. The juices in these fruits can change the way your body treats or breaks down everolimus. The amount of study drug you take and the time when you take it may be changed during the study. This may be because of test results or side effects that you experience. Your study doctor PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**
NIH-2514-1 (07-09)
NIH-2514-2 (10-84)
P.A.: 09-25-0099 File in Section 4: Protocol Consent may also ask you to stop taking your study drug for a brief time. If this happens, you will be told when it is safe to start taking the study drug again. If study drug is stopped for a while, you may have to go to extra visits at the clinic for your safety. If you have any side effects that do not get better after stopping the study drug for a while, your study doctor may decide to discontinue the drug permanently. During the study, you may discuss with a doctor or health care professional, who is not directly involved in the study, health issues or medical problems related to the study treatment or disclose information related to the study treatment. In this case you should tell your doctor or health care professional that the Novartis drug which is part of the study treatment and information relating to it is Novartis' property and is confidential. Your study doctor will tell you about any changes needed in the way you take the medicine. You must always remember not to throw away your empty study drug containers. Instead, keep them in a safe place and bring them back to the doctor's office whenever your study doctor or nurse asks you to. At the end of the study, any study medicine or empty containers you still have should be given back to the study doctor. In order to monitor your progress during the study, we will divide the time you are on the study into cycles. One cycle = 4 weeks or 28 days. You will need the following tests and procedures that are part of regular cancer care.  
- Physical evaluation and weight measurement will be done during week 1 of each cycle - Serum pregnancy test (if you are female and can have children) will be done during week 1 of each cycle.  
- Urine tests will be done during week 1 of each cycle.  
- Vital signs will be taken every 2 weeks. - Blood tests will be performed at 2 weeks until the end of cycle 3 and then during week 1 of each cycle.  
- CT scan of chest/abdomen/pelvis or MRI with or without a bone scan will be performed every 12 weeks.  
- FDG-PET (if your cancer is known or suspected to have spread outside the kidney) and bone scan (if it is suspected that your tumor has spread to your bones) at the start of the study. This may be repeated at one or more times while you are on the study if considered important to make clinical decisions about the management of your cancer.  
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**  
NIH-2514-1 (07-09)  
NIH-2514-2 (10-84)  
P.A.: 09-25-0099  
File in Section 4: Protocol Consent  
- Tests for hepatitis if your doctor determines that you are at risk as needed for the duration of the study and during follow-up.  
You will need the following tests or procedures that are not usually part of regular cancer care to help us monitor your safety  
- Record when you take your medication and any symptoms that you experience in a diary provided by the study team
You will also need the following tests for research to see how the drug is affecting your body and other research studies.  
- Tumor biopsy (optional) will be collected at the beginning of the study before you have taken any study drug and then at approximately 8 weeks (the end of cycle 2). The tumor samples we obtain will be used to look for special markers that may be helpful in the study of kidney cancer and in understanding the effect of the study drugs on the tumor. Results of research done on your specimens and data will not be available to you or your doctor. A separate consent form will be provided to you at the time of the biopsy for you to grant permission to that procedure if you agree to the biopsies.  
- At the beginning of the study, we would like to obtain your previously collected tumor tissue if it is available. We would like to test your tissue for genes that may be linked to cancer.
Clinical trial: NCT02504892
Section: Participant's Rights
Subsections: Research Subject'S Rights What Are The Costs Of Taking Part In This Study?

If you choose to take part in the study, the following will apply, in keeping with the NIH policy:  
- You will receive study treatment at no charge to you. This may include surgery, medicines, laboratory testing, x-rays or scans done at the Clinical Center, National Institutes of Health (NIH), or arranged for you by the research team to be done outside the Clinical Center, NIH if the study related treatment is not available at the NIH.  
- There are limited funds available to cover the cost of some tests and procedures performed outside the Clinical Center, NIH. You may have to pay for these costs if they are not covered by your insurance company.  
- Medicines that are not part of the study treatment will not be provided or paid for by the Clinical Center, NIH.  
- Once you have completed taking part in the study, medical care will no longer be provided by the Clinical Center, NIH.
Clinical trial: NCT02504892
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Risks Or Discomforts Of Participation What Side Effects Or Risks Can I Expect From Being In This Study?|Adverse Drug Reactions|Blood Sampling Risks|Tumor Biopsy Risks|Research Radiation Risks|Potential Benefits Of Participation Are There Benefits To Taking Part In This Study?

While on this study, you may feel side effects. These may be side effects of the study drug, or another medicine. They could also be because of what happens during a study visit, including taking blood. You should discuss any symptoms with the study doctor or your regular doctor. Very common (>10%), common (1% to < 10%), and uncommon (<1%) side effects are listed in this document, but they will be different from person to person. Many side effects go away shortly after the study drug is stopped. In some cases, the side effects may be serious, last a long time or be permanent, and may even cause death. Because certain drugs may increase or decrease the levels of the study drug in your blood, it is important that you follow your study team's instructions about drugs you may or may not take while you are on this study. Please check with your study doctor before taking any medications, including over the counter drugs and herbal medications. Your study doctor will closely follow you during this study, and answer any questions you may have about risks, worries, and side effects. You should talk to your study doctor about any symptoms that you experience while in the study.  
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**  
NIH-2514-1 (07-09)  
NIH-2514-2 (10-84)  
P.A.: 09-25-0099  
File in Section 4: Protocol Consent  
This research study may involve unknown risks. Problems or side effects that are not now known could also occur. You will be given any available new information that may affect your desire to start or continue in the study. Other side effects not mentioned below or observed in previous studies with the drug are also possible. All problems or side effects need to be reported to the study doctors or study nurses looking after you either by phone or at the next visit. For more information about risks and side effects, you should feel free to ask your study doctor. If you are concerned about your health between visits due to being in this study, please call the emergency telephone numbers provided at the end of this document.

One of the most common possible side effects of the study drug is mouth lining tenderness (called stomatitis) ranging from redness, irritation, and swelling, to mouth ulcers (sores in the mouth). This side effect is found in more than half of patients treated with everolimus. Additional very common side effects of everolimus occurring in more than 10% of patients include: fatigue, weakness (feeling weak or tired), chills, nausea and vomiting, loss of appetite, weight loss, skin problems such as rash or itching, diarrhea, pain or swelling of the arms or legs, bleeding of the nose, cough, shortness of breath, and headache. High levels of sugar in the blood, high levels of lipids (cholesterol) in the blood, abnormal or loss of taste, low levels of red blood cells, infections, and spontaneous bleeding or bruising could occur while taking everolimus. Everolimus may cause changes in the lungs. Very commonly, everolimus may be associated with inflammation in the lungs (pneumonitis). Generally mild, it has been severe in a few cases, although it resolves once the treatment is stopped. The consequences of these changes in patients with BHD associated lung cysts has not been previously studied and may be different from that in the general population. Rarely, everolimus is associated with a blood clot or blockage in your lungs or extremities. Tell your doctor right away if you experience new or worsening lung or breathing symptoms like cough or shortness of breath, even when symptoms are mild, as this might have life-threatening consequences. If you experience these symptoms, your study doctor may ask you to undergo chest CT scans and/or a pulmonary function test to evaluate the cause and seriousness of these symptoms. Common side effects (1% to <10%) of everolimus include: dry mouth, dehydration, skin changes (acne, rash, redness, dryness or irritation, itching and skin inflammation), abdominal pain, stomach virus, passing gas, constipation, irritability, nail disorders, increased blood pressure, joint stiffness or pain, mouth pain, difficulty swallowing, (heartburn), fever, insomnia, inflammation of the lining of the digestive system and other mucous membranes such as the sinus, stomach pain, bleeding, and low white blood cells (leukopenia, lymphopenia and neutropenia). As noted above, there could be a lowering of the number of your blood cells that help fight infection. This could lead to an infection (which could be potentially life-threatening). Examples of infections are common colds (sore throat, runny nose), throat infections, pneumonia, urinary tract infections, and ear infections. Therefore, it is important that your blood counts be regularly checked by your study doctor. In addition, there could be a lowering of the blood cells that help the blood to clot (which could cause you to bleed more easily), and a lowering of the protein in your blood (hemoglobin) that helps carry oxygen; this could lead to anemia. Drugs like everolimus can cause the patient's immune system not to work as well as usual. A patient with hepatitis B or hepatitis C who takes everolimus could be susceptible to the virus becoming more active. If you have active hepatitis B or C, you will not be allowed into the study. Changes to the levels of blood sugar (glucose), which could lead to diabetes, could occur while taking everolimus, so your blood sugar levels will be checked often during the study. If you are taking another medicine which may increase blood sugar levels, more frequent monitoring may also be required. Another diabetes test (Hemoglobin A1c) will be checked at the beginning of the study. Everolimus may have an effect on the liver. There could also be an increase in your blood of a waste product of your liver (bilirubin), which could mean that your liver is not working as well. These will be tested regularly during the study. The levels of cholesterol and triglycerides (fats in your blood) could increase. Increased levels of cholesterol and triglycerides are an important factor of risk for heart disease, so your blood cholesterol and triglyceride levels will be regularly checked in this study. Also, your doctor may prescribe medical treatment as appropriate. The levels of liver enzymes (transaminases), which are signs of liver function/damage, may also increase. Everolimus may cause toxicity to your kidneys and cause the levels of creatinine in your blood and protein in your urine to increase. These increases are an indication that the kidneys are not working as well as they did before. This toxicity could lead to kidney failure. Therefore, your blood creatinine levels and urine protein levels (and other urine tests) will be regularly monitored in this study. In addition, there could be a lowering of electrolytes (potassium, phosphate), which are also markers of kidney function, and will be monitored during the study. Everolimus may contribute to increased levels of an enzyme called blood lactate dehydrogenase which gives information about the health of certain organs.  
Other, uncommon side effects (<1%) include the following: Severe decrease in red blood cells or all blood cells, loss of taste, rash of small blisters, bronchitis, coughing up of blood and congestive heart failure (fluid build-up and shortness of breath) as well as non-cardiac chest pain and impaired wound healing, increased daytime urination, inflammation of the gallbladder known as cholecystitis, and elevated number of white cells in the colon with inflammation  
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**  
NIH-2514-1 (07-09)  
NIH-2514-2 (10-84)  
P.A.: 09-25-0099  
File in Section 4: Protocol Consent  
known as eosinophilic colitis. An eye condition known as Anterior Uveitis (inflammation of the eye) has been observed in a very small number of patients. For women of child-bearing potential taking everolimus, changes to your menstrual period (menstruation) may occur. These changes may include: delayed or missing one or more menstrual period (secondary amenorrhea), increased or decreased blood flow during menstruation, or any other irregular change to your menstrual cycle. Also, a hormone called luteinizing hormone (LH) and follicle stimulating hormone (FSH) may be increased due to everolimus. Fertility may be affected. If you experience any hypersensitivity or signs of serious allergic reaction such as rash, itching, hives, difficulty breathing or swallowing, dizziness, signs of serious allergic reaction, please contact your doctor. You should not receive live vaccines and have close contact with people who have received live vaccines within 7 days of starting everolimus and while on this study without consultation with your study doctor. Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella (Chicken Pox), and typhoid vaccines.

Taking blood may cause some discomfort, bleeding or bruising where the needle enters the body, and in rare cases, it may result in fainting. There is a small risk of infection. Some people have not felt well when having their blood taken. Some people have felt dizzy while having their blood drawn or after. Let the nurse know if you would prefer to lie down while you have your blood drawn.

The biopsy procedure usually causes only brief discomfort at the site from which the biopsy is taken. Rarely, infection or bleeding may occur at the needle site.

The biopsy may be done under CT guidance. If that is the case, then this research study involves exposure to radiation from up to 2 CT scans. 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 0.29 rem which is below the guideline of 5 rem (or 0.5 rem in children) 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.  
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**  
NIH-2514-1 (07-09)  
NIH-2514-2 (10-84)  
P.A.: 09-25-0099  
File in Section 4: Protocol Consent  
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. It is best to avoid radiation exposure to unborn or nursing infants since they are more sensitive to radiation than adults.

The aim of this study is to see if this experimental treatment will cause your tumors to shrink. The benefits of everolimus are not established for people with your medical condition. We do not know if you will receive personal, medical benefit from taking part in this study. These potential benefits could include shrinking of your tumor or lessening of your symptoms, such as pain, that are caused by the cancer. Because there is not much information about the drug's effect on your cancer, we do not know if you will benefit from taking part in this study, although the knowledge gained from this study may help others in the future who have cancer.
Clinical trial: NCT02504892
Section: Purpose of Research
Subsections: Description Of Research Study Before You Begin The Study

You will need to have the following exams, tests or procedures to find out if you can be in the study. These exams, tests or procedures are part of regular cancer care and may be done even if you do not join the study. However, there are some extra exams, tests and procedures that you will need to have if you take part in this study. If you have had some of them recently, they may not need to be repeated.  
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**  
NIH-2514-1 (07-09)  
NIH-2514-2 (10-84)  
P.A.: 09-25-0099  
File in Section 4: Protocol Consent  
These tests include:  
- History and physical evaluation including vital signs - Routine blood and urine tests
- Serum pregnancy test (if you are female and can have children)
- CT scan of chest/abdomen/pelvis or MRI - Brain MRI or brain CT
- CT scan of neck (if it is suspected that your tumor has spread to your neck)
- Bone scan (if it is suspected that your tumor has spread to your bones)
- FDG-PET (if your cancer is known or suspected to have spread outside the kidneys) - Tests to measure how well your lungs function - Electrocardiogram (EKG) - Tests for hepatitis if your doctor determines that you are at risk
Clinical trial: NCT02504892
Section: Withdrawal from Study
Subsections: When You Are Finished Taking The Drugs (Treatment)|Stopping Therapy

We would like to see you again within 4 to 5 weeks after you have finished taking the study drug in order to perform the following tests:  
- Physical evaluation and blood tests - CT or MRI for chest, abdomen, pelvis, bone scan if your doctor determines that you may need it.  
- Tests for hepatitis if your doctor determines that you are at risk.
After you have completed this visit, we would also like to contact you by telephone approximately every 3-6 months to find out how you are doing.  
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**  
NIH-2514-1 (07-09)  
NIH-2514-2 (10-84)  
P.A.: 09-25-0099  
File in Section 4: Protocol Consent

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 Novartis 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.