Clinical trial: NCT03302247
Section: Alternatives
Subsections: Are There Benefits To Taking Part In The Study?|What Other Choices Do You Have If You Do Not Take Part In This Research Study?

Taking part in this study may or may not make your health better. While doctors hope that nivolumab in combination with gemcitabine will be more useful against cancer compared to the usual treatment, there is no proof of this yet. We do know that the information from this study will help doctors learn more about the combination therapy as a treatment for non-small cell lung cancer. This information could help future cancer patients.

Your other choices may include:
Getting treatment or care for your cancer without being in a study Taking part in another study Getting no treatment 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, but instead tries to improve how you feel. Comfort care tries to keep you as active and comfortable as possible.
Talk to your doctor about your choices before you decide if you will take part in this study.
Clinical trial: NCT03302247
Section: Confidentiality
Subsections: Will Your Medical Information Be Kept Private?|5. How Will Information About Me Be Kept Private?

We will do our best to make sure that the personal information in your medical record will be kept private. However, we cannot guarantee total privacy. Your personal information may be

The sponsor will keep all patient information private to the extent possible, even though the sponsor is not required to follow the federal privacy laws. Only researchers working with the sponsor will have access to your information. The sponsor will not release personal health information about you to others except as authorized or required by law. However, once your information is given to other organizations that are not required to follow federal privacy laws, we cannot assure that the information will remain protected. However, the laws of the Commonwealth of Pennsylvania or your state of residence may provide further privacy protection.
Clinical trial: NCT03302247
Section: Duration of Study Involvement
Subsections: After You Stop Taking The Study Drug Safety Follow-Up|Follow-Up|Long-Term Follow-Up|How Long Will You Be In The Research Study?

We will perform a safety follow-up 30 days after discontinuing the treatment. In this follow-up visit we will perform the following tests and procedures.  
We will ask you about the medicines that you are taking We will do a physical exam including weight and vital signs We will ask about your ability to do your daily activities Routine blood test ( 1 tablespoon)
Optional blood for future research and banking (1.5 tablespoon).  
We will ask you about any side effects you may be experiencing

If you discontinued the study treatment due to reasons other than disease progression we would do follow-up visits to check the status of your disease. In this visit we will perform the following tests and procedures.  
We will ask you about the medicines that you are taking We will do a physical exam including weight and vital signs We will evaluate your cancer by doing a CT scan once every 8 weeks.  
We will ask you about any side effects you may be experiencing.

We will follow-up via a phone call once every 3 months to check your overall health after it is confirmed that your disease has worsened (disease progression).

You will be asked to take the study drug/s as long you are benefiting from the treatment or your disease does not get worse. You will also be removed from the study if your doctor thinks that you have unacceptable toxicities due to the study drug/s and it is in your best interest that you stop participating in the study.
Clinical trial: NCT03302247
Section: Participant's Rights
Subsections: What Are Your Rights If You Take Part In This Research Study?|10. What Are My Rights Regarding Access To My Personal Health Information?

Taking part in this research study is your choice. You may choose either to take part or not to take part in the research study. If you decide to take part in this study, you may leave the study at any time. No matter what decision you make, there will be no penalty to you and you will not lose any of your regular benefits. Leaving the study will not affect your medical care. You can still get your medical care from our institution. In the case of injury resulting from this study, you do not lose any of your legal rights to seek payment by signing this form.

You have the right to refuse to sign this permission form. You have the right to review and/or copy records of your protected health information kept by Fox Chase Cancer Center and Temple University affiliates. However, while the research study is in progress, you may not be able to access your protected health information in order to preserve the integrity of the research. You will be able to access this information when the study is completed. You do not have the right to review and/or copy records kept by the sponsor or other researchers associated with the research study.  
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Signatures I agree that my protected health information may be used for the research purposes described in this form.
Clinical trial: NCT03302247
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: What Side Effects Or Risks Can You Expect From Being In The Research Study?|Likely (≥ 5%)|Less Likely (2-4%)|Please Inform Your Study Doctor Or Nurse At Once If You Experience Any Of The Following:|Rare But Serious (<2%)|Less Likely (5-19%)|Rare But Serious (<5%)|Radiation Risk For Diagnostic Imaging|Reproductive Risks|For Women Who Can Become Pregnant:|For Men:|For Women And Men:|What If You Are Injured While Taking Part In This Research Study?|Risks

You may have side effects while on the research study. Everyone taking part in the research 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 medicines to help lessen side effects. Many side effects go away soon after you stop taking the nivolumab and/or gemcitabine. In some cases, side effects can be serious, long lasting, or may never go away. There is also a risk of death You should talk to your study doctor about any side effects that you have while taking part in the research study.  
Risks and side effects related to the **nivolumab** include those which are:

Fatigue - feeling tired Skin reactions - including rash, itching, hives, redness, and dry skin Hyponatremia (low sodium levels in the blood) - symptoms may include nausea and vomiting, loss of appetite, headache, confusion, fatigue, restlessness and irritability, muscle weakness, spasms or cramps, decreased consciousness, seizures or coma.  
Diarrhea - increased frequency of bowel movements with loose, watery stools Nausea Abdominal pain Decreased appetite Anemia (low hemoglobin, low hematocrit or low red blood cell count) - red blood cells carry oxygen and nutrients throughout the body. Symptoms that may be experienced as a result of low red blood cell counts may include feeling tired and weak, shortness of breath, increased heart rate, dizziness or lightheadedness, headache, chest pain and pale skin.  
Fever Joint pain or stiffness

Protocol version date: 03/27/2018 Bowl inflammation Liver function blood test abnormalities Loss of color (pigment) from areas of skin Thyroid gland abnormalities Blood chemistry abnormalities, including low blood phosphate, magnesium, and potassium levels High blood uric acid level Dizziness Low white blood cells Pain in arms and legs Peripheral neuropathy - numbness and tingling in the hands and feet Allergic reaction during or between drug infusion Cough Dry Mouth Vomiting - throwing up Weight loss Headache Chills Muscle soreness, weakness, stiffness, spasms or paralysis Shortness of breath Abnormal taste Flushing High or low blood pressure Increased sensitivity of skin to sunlight Constipation Difficulty swallowing Heartburn Thrombocytopenia (low platelet count) - platelets are important in stopping bleeding. A
low platelet count can increase the time to form a blood clot Pneumonitis (Lung inflammation - see below)
Lung Inflammation: It is possible that nivolumab may cause inflammation of the tissues of the lung. This adverse effect has been reported infrequently in patients treated with nivolumab. While many patients with x-ray or CT abnormalities have not developed any symptoms, some patients have developed mild to severe symptoms and in rare cases, death has occurred as a result of their lung inflammation.  
Signs and symptoms of lung inflammation may include difficulty breathing, pain or discomfort while breathing, chest pain, cough, shortness of breath, increased rate of breathing, fever, low blood oxygen levels, or fatigue. Your study doctor and nurse will watch you closely for changes in your ability to breathe and for other signs or symptoms that might show you are developing this type of lung inflammation and will perform regular tests including physical exams, measurement of oxygen levels through non-invasive testing (i.e., pulse oximeter), blood tests, chest x-rays and/or CT scans.

Any new or increased shortness of breath; Any new or increased chest pain; Any new or increased pain/difficulty while breathing; Any new or increased cough or any significant change in your type of cough; for example any new or increased mucous or blood in your cough; Any change in the amount of oxygen you require; Any fever, fatigue, or other symptoms that occur at the same time as any changes to your breathing or other lung symptoms.
If you start to develop symptoms, your study doctor will ask you to return to the clinic for additional tests, which could include a physical exam, measurement of oxygen levels, blood tests, chest x-rays, and/or CT scans. You will be monitored very closely for changes in your overall lung symptoms, monitoring may require hospitalization. You may require specific treatment in order to control pneumonitis. You may also be seen by a special doctor called a pulmonologist, who has special training to be an expert in how your lungs work.  
Prolonged treatment with medicines that suppress inflammation, sometimes needed to manage the side effects of nivolumab treatment, may lower your body's ability to fight off certain infections (i.e., opportunistic infections). These infections may require treatment with antibiotic or antifungal medications and may be fatal.

Low blood oxygen level Acute lung injury or failure Collection of fluid around the lungs Inflammation of the appendix Increase in inflammatory blood proteins (e.g., lipase) Adrenal gland abnormalities Pituitary gland inflammation Changes in vision (including decreased or blurry vision), inflammation of the eye, or bleeding into the eye
Liver inflammation Acute kidney injury or failure Abnormal blood cell production Inflammation of the mouth and lining of the digestive tract Swelling of the face, arms, or legs Inflammation of the pancreas Back pain Autoimmune disorders, including Guillain-Barre syndrome (associated with progressive muscle weakness or paralysis)
Chest discomfort Heart palpitations Inflammation of the heart or its lining Collection of fluid around the heart Increased blood sugar Dehydration Infections: including sepsis, lung infections, and skin infections.  
Decreased movement of the intestines Disorientation Swelling of the optic disc Inflammation of the optic nerve Inflammation or loss of the lining of the brain and spinal cord Drug reaction with rash, blood cell abnormalities, enlarged lymph nodes, and internal organ involvement (including liver, kidney, and lung); known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
Myasthenia gravis, a nerve disease that may cause weakness of eye, face, breathing, and swallowing muscles. One death in a patient who received nivolumab combined with ipilimumab was considered due to myasthenia gravis and severe infection (sepsis).  
Abnormal brain function due to brain inflammation (encephalitis), potentially lifethreatening or fatal.  
Toxic epidermal necrolysis, a potentially fatal disease characterized by blistering and peeling of the top layer of skin resembling a severe burn, has occurred in patients who received nivolumab treatment.  
Rhabdomyolysis (muscle fiber released into the blood stream which could damage your kidney) and polymyositis (chronic muscle inflammation with muscle weakness) has been reported in one patient.  
Risks and side effects related to the **gemcitabine** include those which are: Likely (≥ 20%)
Leukopenia/Neutropenia (low white blood cell count) - a low white blood cell count makes it hard for you to fight infections Thrombocytopenia (low platelet count)– platelets are important in stopping bleeding. A low platelet count can increase the time to form a blood clot, causing you to bruise or bleed more easily Anemia (low hemoglobin, low hematocrit or low red blood cell count) Red blood cells carry oxygen and nutrients throughout the body. Symptoms that may be experienced as a result of low red blood cell counts may include feeling tired and weak, shortness of breath, increased heart rate, dizziness or lightheadedness, headache, chest pain and pale skin Nausea - feeling sick to your stomach Vomiting - throwing up

Hair loss Mucositis/stomatitis - sores in the lining of your mouth and/or throat that can be painful and make it hard to swallow Peripheral neuropathy - numbness and tingling in hands and feet Somnolence - feeling sleepy Radiation recall - redness, burning, shedding or peeling of the skin where you have had radiation Elevation in serum creatinine, an enzyme in your blood, which may or may not indicate damage to your kidneys

Congestive heart failure - a decrease in the heart's strength and ability to pump blood to the rest of the body Heart attack - symptoms may include chest pain/tightness, shortness of breath, nausea, sweating and dizziness Changes in heart rhythm Stroke - symptoms may include a sudden numbness or weakness of the face, arms or legs (usually on one side of the body), dizziness, severe headache, confusion, difficulty speaking or understanding, trouble walking and a sudden loss of balance Kidney failure Liver failure Pneumonitis - inflammation of the lungs which may cause shortness of breath, chest pain and cough Reversible Posterior Leukoencephlopathy Syndrome (RPLS) - a neurological disorder which can present with a headache, confusion, seizures, vision changes  
Rash , with or without itching, usually over the legs (but can be on other parts of your body)
Diarrhea - increased frequency of bowel movements with loose watery stools Elevated liver enzymes - liver enzymes are proteins made by the liver that are measured in the blood, with a blood draw. Liver enzymes indicate how well your liver is functioning. Elevated liver enzymes may cause no symptoms, however higher liver enzyme levels may cause you to feel overly tired or weak, you may bruise or bleed more easily, and you may experience abdominal pain or have a yellowing of the skin or eyes Hyperbilirubinemia (elevated bilirubin levels in the blood) - bilirubin is a chemical that is released when red blood cells are broken down. Bilirubin is used by the liver to make bile. Symptoms of elevated bilirubin levels include a yellowing of the skin, eyes and mucous membranes Flu-like symptoms including fever, chills, muscle aches and pain Fever Pain, including bone pain Fluid retention, swelling of the hands, legs or feet Shortness of breath Proteinuria - abnormal levels of protein in the urine, which may indicate kidney damage Small amounts of blood in your urine (may indicate a problem with your kidneys)
Constipation - difficulty having a bowel movement Tissue Necrosis - the death of body tissue which occurs when there is not enough blood flowing to the tissue. Necrosis is not reversible. When large areas of tissue die due to a lack of blood supply, the condition is called gangrene.  
Capillary leak syndrome - a condition in which fluid and proteins leak out of tiny blood vessels and flow into other tissues, resulting in dangerously low blood pressure

It is unlikely that there will be any harmful effects from the radiation exposure you will receive from participating in this study.  
At high levels of exposure, scientists agree that radiation can cause cancer. At low exposure levels most scientists agree that the risk, if any, is very low. You will have low levels of radiation exposure with diagnostic imaging procedures.  
Risks from exposure to radiation may accumulate over a lifetime.  
Blood Draw Risks Fainting Bleeding Bruising at the place on your arm where the blood was drawn or needle inserted Pain Swelling Infection (rare)
Biopsy Risks Bleeding Pain Infection, which can be life-threatening or fatal in rare cases

The drugs in this study may affect a baby, before or after the baby is born.  
You should not become pregnant or father a baby while on this research study because the drugs you take could possibly hurt an unborn baby.  
If you are pregnant now or if you are breast-feeding now, you may not take part in this research study.  
If you become pregnant while you are on the research study, you may not continue to take part in the research study. Your pregnancy will be reported to Bristol Myers Squibb, the manufacturer of nivolumab, and followed for outcome.

You should not become pregnant while you are in this study and up to 23 weeks from the last dose of nivolumab.  
You should not breast-feed your baby while taking drugs for this research study and up to 23 weeks from the last dose of nivolumab.  
You will have a pregnancy test within first 24 hours of your first dose of nivolumab and then once every cycle during the course of this study.  
If you become pregnant, suspect pregnancy or if you missed your period or it is late, or if you have a change in your usual menstrual cycle (e.g., heavier bleeding during your period or bleeding between periods), you should immediately contact your study doctor.  
You are expected to use one of the highly effective methods of contraception listed below.  
Progestogen only hormonal contraception associated with inhibition of ovulation Hormonal methods of contraception including oral contraceptive pills
(combination of estrogen and progesterone), vaginal ring, injectables, or implants Intrauterine devices (IUDs) (hormonal or non-hormonal) Intrauterine Hormone-releasing System (IUS) Bilateral tubal ligation Vasectomy Complete abstinence (complete avoidance of heterosexual intercourse)

You should not make a woman pregnant while you are in this study and up to 31 weeks after the last dose of nivolumab.  
If you are with female partners who are women of child bearing potential, you are expected to use condoms as the method of contraception You should immediately contact your study doctor if your female partner becomes pregnant while you are in this study. If your partner does become pregnant, it will be reported to Bristol Myers Squibb and followed for outcome.

Check with the study doctor about birth control methods and how long to use them.  
Some methods might not be approved for use in this study.

If you are injured as a result of your participation in this research study, seek immediate medical care. Temple University Health System or its subsidiaries will treat the injury, though there is no commitment to provide monetary compensation or free medical care. Other financial compensation (such as lost wages or pain and suffering) for such injuries is not available.

The greatest risk to you is the release of information from your health records. We will do our best to make sure that your personal information will be kept private. The chance that this information will be given to someone else is very small.
Clinical trial: NCT03302247
Section: Procedures
Subsections: What Will Happen If You Take Part In This Research Study? Before You Begin The Research Study|During The Research Study Study Treatment|Tests And Procedures

You will need to have the following exams, tests or procedures to find out if you can be in the research study. These exams, tests or procedures are part of regular cancer care and may be done even if you do not join the research study. If you have had some of them recently, they may not need to be repeated. This will be up to your study doctor.  
Protocol version date: 03/27/2018  
We will ask you about your medical history and medicines you are taking We will do a physical exam which will include height, weight and vital signs We will ask about your ability to do your daily activities Routine blood tests (1 tablespoon)
We will check your heart function by performing an EKG
o EKG is a test to measure the electrical activity of your heart Blood for pregnancy test (2 teaspoon), if you are a female and able to become pregnant.  
We will evaluate your cancer by doing a CT scan o A CT scan is a computerized x-ray that gives your study doctor pictures of the inside of your body.  
A biopsy sample is required for entry in the study if a standard of care test for determining the expression of a biomarker is not already done. If you have the testing done we will request tissue sample from you but this is optional. A biopsy is a small piece of tissue from your cancer.

If the screening procedures show you can take part in the study, you will receive nivolumab intravenously over a period of 30 minutes on day 1 and then on day 15 of the treatment cycle. In addition, you will also receive gemcitabine intravenously over a period of 30 minutes on day 1, day 8 and day 15 of the treatment cycle. Gemcitabine will be administered before nivolumab administration. **Each treatment cycle is 28 days**. Once a treatment cycle ends the next treatment cycle will begin. If during the treatment your study doctor determines that you are having unacceptable side-effects due to nivolumab, you may receive only gemcitabine for the rest of the study.

If the exams, tests and procedures show that you can be in the research study, and you choose to take part, then you will need the following tests and procedures. They are part of regular cancer care. Some of these tests are being done more often because you are in this research study.  
We will ask you about all the medicines you are taking We will do a physical exam which will include vital signs and weight We will ask about your ability to do your daily activities Routine Blood tests (1 tablespoon) - once every cycle. Blood for pregnancy test (2 teaspoons), if you are a female and able to get pregnant –
once every cycle We will ask you about any side effects you may be experiencing. We will check your heart function by performing EKG, however this test will be performed only if your study doctor recommends.  
We will assess your tumor by performing a CT scan - once every 8 weeks Blood for research on day 1, 8, 15 of cycle 1, and day 1 of cycles 2, 3 (up to 1.5 tablespoons)
Optional blood collection for future research and banking (1.5 tablespoon) - every other cycle starting from cycle 1.
Clinical trial: NCT03302247
Section: Purpose of Research
Subsections: Why Is This Research Study Being Done?|1. What Is The Purpose Of This Form?

The purpose of this research study is to see if MDSCs are altered in patients receiving Gemcitabine in combination with Nivolumab. MDSCs are a type cells that are thought to play a role in suppressing immune response against cancer. Nivolumab is an antibody (a type of human protein) that is being tested to see if it will allow the body's immune system to work against tumor cells. Gemcitabine is a drug that is already approved by FDA to treat patients with non-small cell lung cancer. The combination of nivolumab and gemcitabine is not yet approved for treating non-small cell lung cancer.  
We do not know if you will benefit from this research study. It is possible that your condition will get better, but it is also possible that there will be no effect on your condition or that your condition will get worse. We can use what we learn from this research study to help other people with the same disease.

This form is required by the Health Insurance Portability and Accountability Act of 1996. Specifically the privacy regulation (HIPAA) permits the research investigators listed above to use and disclose health information about you for the research study identified above which has been approved by the Fox Chase Cancer Center Institutional Review Board. The sponsor is an organization/person that does research to learn about the causes of cancer, and how to prevent and treat cancer. Researchers would like to use your protected health information for research. The elements of protected health information as defined by HIPAA are:
Clinical trial: NCT03302247
Section: Withdrawal from Study
Subsections: Can You Stop Being In The Research Study?|Can You Be Removed From This Research Study?|8. What Happens If I Want To Withdraw My Permission?

Yes. You can decide to stop at any time. Tell the study doctor if you are thinking about stopping or decide to stop. He or she will tell you how to stop safely. It is important to tell the study doctor if you are thinking about stopping so any risks due to the study nivolumab and/or gemcitabine can be evaluated by your doctor. Another reason to tell your doctor that you are thinking about stopping is to discuss what followup care and testing could be most helpful for you.

The study doctor may stop you from taking part in this research study at any time if he/she believes it is in your best interest; if you do not follow the research study rules; or if the research study is stopped.

You can change your mind at any time and withdraw your permission to allow your protected health information to be used in the research. If this happens, you must withdraw your permission in writing. Beginning on the date you withdraw your permission, no new protected health information will be used for research. However, researchers may continue to use the protected health information that was provided before you withdrew your permission. If you sign this form and enter the research study, but later change your mind and withdraw your permission, you will be removed from the research study at that time.  
To withdraw your permission, please contact the person below. He will make sure your written request to withdraw your permission is processed correctly.  
Contact Name: Martin J Edelman  
Contact Address: 333 Cottman Avenue  
Philadelphia, PA 19111  
Contact Phone and  
FAX:  
215-728-4300 and 215-728-3639  
9. How long will this permission last? If you agree by signing this form that researchers can use your protected health information, this permission has no expiration date. However, as stated above, you can change your mind and withdraw your permission at any time.