Clinical trial: NCT02579811
Section: Confidentiality
Subsections: Privacy And Confidentiality

If you volunteer to participate in this research, your protected health information (PHI) that identifies you will be used or disclosed to Moshe Ornstein, MD and the research staff at Cleveland Clinic for the purposes of this research and to Case Western Reserve University for administration. The PHI that we may use or disclose (release) for this research may include your name, address, phone number, date of birth, Social Security number, information from your medical record, lab tests, or certain information relating to your health or condition. Some of the tests and procedures done solely for this research study may also be placed in your medical record so other doctors know you are in this study. Upon completion of the study, you may have access to the research information that is contained in your medical record. In addition to the investigators and research staff listed above, your PHI may be looked at by other groups involved with the study such as the Cleveland Clinic Institutional Review Board and the Case Comprehensive Cancer Center Protocol Review and Monitoring Committee. Your PHI may also be used by and/or disclosed (released) to:  
x Pfizer, the study sponsor; x The Food and Drug Administration; x The Department of Health and Human Services; x The National Cancer Institute (NCI); x Other Institutional Review Boards; x Data Safety and Monitoring Boards;
Once your personal health information is released it may be re-disclosed and no longer protected by privacy laws. Your research information may be used and disclosed indefinitely, but you may stop these uses and disclosures at any time by writing to: Moshe Ornstein, M.D. Cleveland Clinic Taussig Cancer Center 9500 Euclid Avenue/Desk CA-60 Cleveland, Ohio 44195 Phone: 216-445-6592 Your participation in the research will stop, but any information previously recorded about you cannot be removed from the records and will continue to be used as part of this research. Also, information already disclosed outside the Cleveland Clinic cannot be retrieved. This will not affect your rights to treatment or benefits outside the research study. The Cleveland Clinic will not use your information collected in this study for another research purpose without your written permission; unless the Cleveland Clinic Institutional Review Board (IRB) assures your privacy and confidentiality is protected. The IRB is a committee whose job it is to protect the safety and welfare of research subjects. By signing this informed consent form, you are authorizing such access to your research and medical record information. If you choose not to sign this consent form, you will not be able to participate in this research study. This Authorization does not have an expiration date.
Clinical trial: NCT02579811
Section: Duration of Study Involvement
Subsections: Screening Visit:|First 14 Days / 2 Weeks On The Clinical Trial|Every 2 Week / 14 Days|Every 4 Weeks / 28 Days|Every 8 Weeks

This visit takes place within the four weeks before you start the medication. During this visit, your team will perform a physical exam on you and order some blood work listed in the table above to determine whether you qualify for the study. You will also have a fullbody CT scan done if you have not had one within 28 days of when you are scheduled to start on this clinical trial.

Every 28 days on this clinical trial is called a "cycle." The starting dose of axitinib is 5mg taken twice a day. 1 week and 2 weeks after starting axitinib we will contact you by phone to ask about any side effects you are experiencing on axitinib. Although there are many possible side effects listed in section 4, the most bothersome are mouth pain, diarrhea, pain in hands and/or feet, and fatigue. Depending of how severe the side effects are we may ask you to stop taking the axitinib for a few days or take a lower dose. If needed, we will arrange for you to see us in clinic.

Every time we change the dose of your medication we reach out to you by phone within seven days later to see how you are tolerating the new dose.  
a. If you are having serious toxicities **within the first week**, the dose of axitinib you are taking will be lowered.  
b. If you are having serious toxicities **within the second week** you will receive a break from the axitinib for a few days and then resume at the same dose.  
c. If you are still doing well on that dose **after 2 weeks**, your dose of axitinib will be increased.
**It is exceedingly important that you follow your medical team's instructions with regard to taking your axitinib at the prescribed dose, holding axitinib when advised, and not restarting axitinib until advised. This is for your safety**

Every 28 days, a new "cycle" begins. At the start of the cycle, we will see you in clinic for a physical examination and to assess the toxicities you are experiencing while on your current dose of axitinib. We will perform blood collection as mentioned in the table above. After 1 year on treatment, doctor visits and study assessements may be done every 12 weeks if your physician feels this is appropriate for you.

In addition to the tests that are done every 4 weeks, at every 8 week mark we will do a full body CT scan. After 1 year on treatment, your CT scans will be done every 12 weeks if your physician feels this is appropriate for you. If you withdraw from the study prior to its completion, you will be asked to return all study medication and, for your safety, come in for a final clinical visit in order to see how you are feeling and assess any side effects.
Clinical trial: NCT02579811
Section: Participant Responsibilities
Subsections: Study Restrictions / Patient Responsibilities / Alternatives To Participation

Regardless of dose level, all doses of axitinib should be taken with food. Axitinib doses should be taken as close to 12 hours apart as possible. If you miss a dose, you may take a "make-up" dose up to 3 hours prior to the next dose. If it is less than 3 hours to your next scheduled dose, please skip the missed dose. If you happen to vomit and lose a dose, please do not make up that dose. It is extremely important to take the specified number of tablet(s) from EACH bottle as instructed, twice daily. If you are given more than one bottle of pills, do not mix the tablets from the different bottles. There are certain medications that may not be good to take while you are taking axitinib. In order to protect your safety while on the study, please let your doctor know of all medications you are taking while you are on study. Your doctor will let you know if your medications can be taken with axitinib. Certain drugs may reduce the amount of axitinib in your blood and their use will not be permitted while on study. In addition it is recommended that you not drink grapefruit juice, eat grapefruit, or take the herbal product St. John's Wort. If you do not wish to participate in this study, you can still be treated with axitinib the way it is usually prescribed. We can also look for a different clinical trial if you would like to consider that.
Clinical trial: NCT02579811
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Risks|Common (Occurs In 1% To 10% Of Patients):|Uncommon (Occurs In Less Than 1% Of Patients):|Risks Of Ct Scans|Reproductive Health/Sexual Activity|Pregnancy|Research-Related Injury

The risks in this study are the risks of the medication axitinib. The following are the side effects of axitinib whether it is taken on this study or not.  
Very Common (occurs in greater than or equal to 10% of patients):
x diarrhea x high blood pressure x fatigue x decrease appetite x nausea x hoarseness x redness and/or pain in hands and feet x weight decreased x vomiting x weakness x constipation x decreased thyroid function x cough x mucosal inflammation x pain in joints x soreness or swelling of the mouth x shortness of breath x abdominal pain x bleeding events (including nose bleeding, blood in urine, rectal bleeding, bleeding from lung/blood in sputum, brain bleeding, gastrointestinal bleeding)
x headache x rash x pain in extremity x protein in urine x disturbance of taste x dry skin

x dizziness x upper abdominal pain x muscle pain x pruritus (itch)
x dehydration x nose bleed x hemorrhoids x hair loss x decrease in red blood cell count (the oxygen carrying cells)
x ringing in ear x pain or burning feeling of the tongue x elevation in blood calcium and/or potassium x elevation of blood lipase and amylase (may be a sign of altered pancreatic function)
x elevation of blood creatinine (may be a sign of altered kidney function)
x erythema (redness of skin)
x elevation of liver function blood test (such as ALT, AST, and alkaline phosphatase) x sudden blocking of vein or artery by a clot of blood cell (blood clot in body and leg, or in lung, in eye causing visual disturbance/change in vision, transient ischemic attack (stroke), myocardial infarction (heart attack), cerebrovascular accident (stroke)),increased thyroid function x wound healing complication, heart problems (heart failure/congestive heart failure, ventricular dysfunction/failure (meaning your heart does not pump normally and could lead to symptoms such as fatigue, breathing problems and swelling), both heart and lung failure, heart attack, decrease of heart pump efficiency

x increase of red blood cell or hemoglobin x elevation of bilirubin blood test x hypertensive crisis (severe, sudden increase in blood pressure)
x transient ischemic attack x visual disturbance/change in vision x blood clot in body x reversible posterior leukoencephalopathy syndrome which has possible symptoms of headache, confusion, drowsiness, difficulty seeing, and seizures x tumor destruction leading to hole in the intestine (perforation) x fistula (abnormal tube-like passage from one normal body cavity to another body cavity or the skin)

If you take part in this research, you will have one or more medical imaging studies which use radiation. The imaging studies will include a CT scan. To give you an idea about how much radiation you will get, we will make a comparison with an every-day situation. Everyone receives a small amount of unavoidable radiation each year. Some of this radiation comes from space and some from naturally-occurring radioactive forms of water and minerals. This research gives your body the equivalent of about 2 extra years' worth of this natural radiation. The radiation dose we have discussed is what you will receive from this study only, and does not include any exposure you may have received or will receive from other tests. The insertion of the needle to draw blood is painful; however, the discomfort is brief. For most people, needle punctures to get blood samples do not cause any serious problems; however, they may cause bleeding, bruising, discomfort, infections, dizziness, or fainting.

There is the potential for effects on male and female reproductive organs that could affect fertility, and the potential for developmental effects to an unborn child.

If you, or your partner, becomes pregnant during the study or within at least 3 months after you have stopped taking the study drug, please tell the study doctor immediately. Please also tell the doctor who will be taking care of you/your partner during the pregnancy that you took part in this study. The study doctor will ask if you/your partner or your pregnancy doctor is willing to provide updates on the progress of the pregnancy and its outcome. If you/your partner agree, this information will be provided to the study sponsor for safety monitoring follow-up.

If you experience physical injury or illness as a result of participating in this research study, medical care is available at Cleveland Clinic or elsewhere; however, Cleveland Clinic will not provide free care or compensation for lost wages. Further information about research-related injuries is available by contacting the Cleveland Clinic Institutional Review Board at (216) 444-2924 For more information on clinical trial and insurance coverage, you can visit the National Cancer Institute's (NCI) website at: http://cancer.gov/clinicaltrials/understanding/insurance-coverage You can print a copy of the 'Clinical Trials and Insurance Coverage' information from this website. Another way to get information is to call 1-800-4-CANCER (1-800-422-6237) and ask NCI for a free copy.
Clinical trial: NCT02579811
Section: Procedures
Subsections: Study Procedures

As a participant in this study, you will be asked to return to the Cleveland Clinic 2 weeks after starting the study and then every 4 weeks. If you need to reach us sooner, we will always be available to talk to you by phone or schedule you for an appointment. Your participation in this study will last for as long as you are taking axitinib. These visits will always take place at the Taussig Cancer Institute at the Cleveland Clinic. The following chart outlines what will happen at these your office visits. The same information is listed in greater detail following the table.  
| Visit/ Phone  call                                                                                                                                                                                                                                          | What will need to be  brought and/or done at  this visit?   |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------|
| What will be done at this visit?  What is the purpose of the phone call?  1. Performance Status (a measure of your  ability to perform certain everyday tasks)  2. Physical Examination (including height,  weight, temperature, blood pressure and  pulse) |                                                             |
| Screening  (prior to  starting  the trial)                                                                                                                                                                                                                  | Please bring a list of all  your medications.               |
| 3. Blood collection for organ function  (chemistry), blood (hematology), thyroid,  and pregnancy (if applicable) (10 mL / ~ 2  teaspoons)  4. Full body CT scan                                                                                             |                                                             |  
| 1 week  and 2  weeks  after  starting  trial                                                                   | A phone call will be made to check on how  you are doing with the current medication  dose.  1. Performance Status (a measure of your  ability to perform certain everyday tasks)  2. Physical Examination (including height,  weight, temperature, blood pressure and  pulse)          | Please bring the diary  sheet we provided and  your axitinib medication  bottle.   |
|----------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------|
| Every  four  weeks                                                                                             | 3. Blood collection for organ function  (chemistry) and blood (hematology), (10 mL  / ~ 2 teaspoons)  1. Performance Status (a measure of your  ability to perform certain everyday tasks)  2. Physical Examination (including height,  weight, temperature, blood pressure and  pulse) | Please bring the diary  sheet we provided and  your axitinib medication  bottle.   |
| Every  eight  weeks                                                                                            | 3. Blood collection for organ function  (chemistry), blood (hematology) ,and  thyroid  2. Full body CT scan. After 1 year of  treatment, CT scans will be done every 12  weeks if your physician feels this is  appropriate for you.                                                    |                                                                                    |
| One week  and two  weeks  after each  dose  change                                                             | Please bring the diary  sheet we provided and  your axitinib medication  bottle.                                                                                                                                                                                                        |                                                                                    |
| A phone call will be made or a clinic visit if  needed to check how you are doing on the  new medication dose. |                                                                                                                                                                                                                                                                                         |                                                                                    |
Clinical trial: NCT02579811
Section: Purpose of Research
Subsections: Consent For Cancer Research|Purpose

Project Title: A PHASE II STUDY OF THE EFFICACY AND SAFETY OF AXITINIB GIVEN ON AN INDIVIDUALIZED SCHEDULE FOR METASTATIC RENAL CELL CANCER AFTER TREATMENT WITH ANTI-PD-1 OR ANTI-PD-L1 INHIBITORS Principal Investigator: Moshe Ornstein, MD Research Nurse: Laura Wood, RN

You are being asked to participate in a research study of axitinib in patients with advanced kidney cancer who have already received therapy for treatment of kidney cancer. Axitinib is a drug which is approved by the FDA for patients with advanced kidney cancer who have already received some treatment. It works by reducing blood flow to a tumor. Axitinib is normally give at 5mg twice per day and sometimes this dose is increased if patients tolerate it. The purpose of this study is to figure out a different way to decide which dose of axitinib each patient should receive based on the side effects they experience. About 40 people will take part in this research study at 4 different hospitals and approximately 27 people will take part at the Cleveland Clinic.
Clinical trial: NCT02579811
Section: Voluntary Participation
Subsections: Voluntary Participation

Your participation in this research study is voluntary. Choosing not to participate will not alter your usual health care or involve any penalty or loss of benefits to which you are otherwise entitled. If you decide to join the study, you may withdraw at any time and for any reason without penalty or loss of benefits. If information generated from this study is published or presented, your identity will not be revealed. In the event new information becomes available that may affect the risks or benefits associated with this study or your willingness to participate in it, you will be notified so that you can decide whether or not to continue participating.
Clinical trial: NCT02579811
Section: Withdrawal from Study
Subsections: Removal From The Study

The study doctor or Pfizer may decide to take you out of the study if:
a. You do not follow the directions of the study doctor b. You develop a serious illness that is not related to taking part in the study c. The study doctor decides that the study is not in your best interest d. Pfizer, the responsible regulatory authority, or Institutional Review Board/Independent Ethics Committee (IRB/IEC) decides to stop the study e. You become pregnant, intend to become pregnant or are nursing a child during this study.