Clinical trial: NCT01928576
Section: Alternatives
Subsections: 7. What Are Your Options If You Do Not Want To Be In The Study?

You do not have to join this study. If you do not join, your care at Johns Hopkins will not be affected. Alternative options may include other chemotherapy, radiation therapy, other investigational research studies, no treatment, or comfort care (palliative care, which is designed to reduce suffering).  
  
Please ask any questions you may have and take as much time as you need to make your decision.
Clinical trial: NCT01928576
Section: Confidentiality
Subsections: Research Participant Informed Consent And Privacy Authorization Form|Consent/Authorization To Obtain Medical Records After Study Regimen Discontinuation: (Mark Choice With An "X")|Consent/Authorization For Use Of Your Tissue For Future Research: (Mark Choice With An "X")

Patient I.D. Plate Protocol Title: A Phase II Study of Epigenetic Therapy **with Azacitidine and**
Entinostat **with Concurrent Nivolumab in Subjects with**
Metastatic Non-Small Cell Lung Cancer. (Protocol Version 13; September 17, 2020)  
| Application No.:        | NA_00084192                                                                                                              |
|-------------------------|--------------------------------------------------------------------------------------------------------------------------|
| Sponsor:                | Stand Up To Cancer; Rising Tide Foundation; Jim Toth                                                                     |
| Principal Investigator: | Julie Brahmer, MD. Skip Viragh Building  201 N Broadway, 8121  Baltimore, MD 21287 Phone: 410-502-7159 Fax: 410-614-9334 |

I agree to allow my medical records to be obtained for this study after study regimen discontinuation.  
I do not agree to allow my medical records to be obtained for this study after study regimen discontinuation. Subject Initials: _________________ Date of Initials: ____________________

I agree to allow my tissue (specimen) to be kept for use in research to learn about, prevent, or treat cancer.  
I do not agree to allow my tissue (specimen) to be kept for use in research to learn about, prevent, or treat cancer. Subject Initials: _________________ Date of Initials: ____________________
I agree to allow my tissue (specimen) to be kept for use in research to learn about, prevent, or treat other health problems (for example: diabetes, Alzheimer's disease, or heart disease).  
I do not agree to allow my tissue (specimen) to be kept for use in research to learn about, prevent, or treat other health problems (for example: diabetes, Alzheimer's disease, or heart disease). Subject Initials: _________________ Date of Initials: ____________________
Clinical trial: NCT01928576
Section: Duration of Study Involvement
Subsections: How Long Will You Be In The Study?

You will be in the study until the lung cancer has progressed. After you are finished with the study regimen, the study doctor will ask you to visit the office for follow-up exams for at least 3 months, and to continue to monitor your health by office visits or by telephone every 12 weeks for 5 years. Keeping in touch with you and checking on your condition helps us look at the long-term effects of the study.
Clinical trial: NCT01928576
Section: Participant's Rights
Subsections: 13. What Is A Certificate Of Confidentiality?|14. What Does A Conflict Of Interest Mean To You As A Participant In This Study?|19. What Does Your Signature On This Consent Form Mean?

Your study information is protected by a Certificate of Confidentiality. This Certificate allows us, in some cases, to refuse to give out your information even if requested using legal means. It does not protect information that we have to report by law, such as child abuse or some infectious diseases. The Certificate does not prevent us from disclosing your information if we learn of possible harm to yourself or others, or if you need medical help. Disclosures that you consent to in this document are not protected. This includes putting research data in the medical record or sharing research data for this study or future research. Disclosures that you make yourself are also not protected.

A researcher has a financial or other interest in this study, which may affect the researcher's judgment when conducting the study.  
  
In some situations, the results of the study may lead to a financial gain for the researcher(s) and/or Johns Hopkins. This interest has been reviewed in accordance with Johns Hopkins' policies and approved with certain conditions If you have any questions about this financial interest, please talk to Dr. Julie Brahmer at 410-502-7159. This person is a member of the study team, but does not have a financial interest related to the study. You may also call the Office of Policy Coordination (410-361-8667) for more information. The Office of Policy Coordination reviews financial interests of investigators and/or Johns Hopkins.

Your signature on this form means that: You understand the information given to you in this form, you accept the provisions in the form and you agree to join the study. You will not give up any legal rights by signing this consent form.
Clinical trial: NCT01928576
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: 4. What Are The Risks Or Discomforts Of The Study? Risks To Azacitidine|The Most Commonly Reported Side-Effects With Azacitidine Treatment Were The Following: Anemia (Decrease In Cells That Carry Oxygen) Low Number Of White Blood Cells With Or Without Fever Infection Especially When White Blood Cell Count Is Low Shortness Of Breath Injection Site Reactions (Inflammation In Or Damage To The Tissue Surrounding Where An Injection Was Given)|Common (≥1%-≤10%) Bone Marrow Failure|Uncommon (≥0.1%- <1%) Hypersensitivity|Risks Of Entinostat Common, Some May Be Serious|Most Common Side Effects (≥ 10%) Of Nivolumab Are: Diarrhea Fatigue Itching Rash|Rare Side Effects Of Nivolumab Include: [≥ 1/10,000 To < 1/1,000 Or > 0.01% To < 0.1%] Anaphylactic Reaction (Severe Allergic Reaction)|Potential Risks - Study Procedures Blood Drawing|Confidentiality Loss|Other Risks Of The Study:|5. Are There Risks Related To Pregnancy?|Reproductive Risks To Nivolumab (Bms-936558) General Statement:|Unforeseeable Risks|15. What Treatment Costs Will Be Paid If You Are Injured In This Study?

You may have side effects while you are in the study, but you will be carefully checked by the study doctor for any problems. There may be risks or side effects of the study drug that are unknown at this time. You should tell the study doctor/staff about anything that is bothering you or any side-effects you may have, even if you do not think they are related to the study drug.

Low blood counts may result in significant anemia, infection, bleeding, and feeling tired and weak. The dosage and treatment schedule of azacitidine will be adjusted if certain levels of toxicity are found in your laboratory results. The following is a list of the most medically significant or most common side effects reported in completed and ongoing studies considered to be related to azacitidine. In some cases, side effects can be serious, long-lasting, may never go away, or can cause death. This is not a complete list of all side effects that may occur. Other side effects not listed here may occur. For more information about risks and side effects, please ask the study doctor. The study doctor may give you medicines to help lessen the side effects.

Low counts for red blood cell, white blood cell and platelets (Pancytopenia)
Red patch appearing in the white of the eye beneath the clear lining of the eye (Conjunctival hemorrhage)
Eye hemorrhage Indigestion (Dyspepsia)
Gastrointestinal hemorrhage (includes mouth hemorrhage)
Bleeding gums/Gingival bleeding Hemorrhoidal bleeding Mouth sores (Stomatitis)
Catheter site hemorrhage Chills Injection site bruising, discoloration, hematoma, hemorrhage, induration, inflammation, nodule, pruritus, and rash Malaise Bacterial skin infection (Cellulitis)
Inflammation or infection of one or more small pouches in the digestive tract (Diverticulitis)
Serious infection (Neutropenic sepsis)
Oral fungal infection Pain or irritation in the throat (Pharyngitis)
Respiratory tract infection (including bronchitis and upper respiratory tract infection)  
  
  
Stuffy nose (Rhinitis)
Sepsis (including bacterial, fungal and viral)
Sinus infection (Sinusitis)
Skin infection Urinary tract infection Blood creatinine increased Dehydration Muscle spasms Stroke (Intracranial hemorrhage)
Lack of energy (Lethargy)
Excess sleepiness (Somnolence)
Loss of consciousness, fainting (Syncope)
Anxiety Blood in urine (Hematuria)
Renal failure Shortness of breath on exertion (Dyspnea exertional)
Laryngeal pain Fluid buildup between the lungs and chest (Pleural effusion) Hair loss (alopecia) Reddening of the skin (Erythema)
Skin lesion Hives (Urticaria)
Bruise (Hematoma)
Hypertension Hypotension Orthostatic hypotension

Additional events not otherwise noted above include: Rapid death of cancer cells where the accumulating contents of dying cancer cells cause an imbalance in the chemistry of the body which can lead to kidney damage.

In 100 people receiving MS-275 (SNDX-275, entinostat), more than 20 may have:
Fatigue (tiredness)
Nausea Decreased number of platelets in the blood that may cause you to bruise easily and for your blood to clot slowly after bleeding Decrease in the number of blood cells that carry oxygen which may cause you to feel tired or short of breath Vomiting Decreased number of a type of white blood cell called neutrophils in the blood which may increase your risk of infection Diarrhea Decreased number of a type of white blood cell called leukocytes in the blood

Common side effects of Nivolumab may include (> 1% - **< 10%):**
Abdominal pain Alkaline phosphatase increased: lab test result associated with liver or bone abnormalities Allergic reaction/hypersensitivity ALT increased: lab test result associated with abnormal liver function Amylase increased: lab test result associated with pancreas inflammation AST increased: lab test result associated with abnormal liver function Bilirubin (liver function blood test) increased Chills Constipation Cough Creatinine increased: lab test result associated with decreased kidney function Decreased appetite Dizziness or vertigo (feeling off balance which can lead to dizziness)
Dry mouth Dry skin Fever Headache Increased blood sugar Inflammation of the colon Inflammation of the mouth Infusion related reaction Lipase increased: lab test result associated with pancreas inflammation Loss of color (pigment) from areas of skin Lung inflammation (pneumonitis - see details below)
Musculoskeletal pain Nausea  
  
  
Redness (of the skin)
Shortness of breath Sodium levels in the blood low Swelling, including face, arms, and legs Thyroid gland function decreased Thyroid gland function increased Thyroid stimulating hormone increased (lab test associated with abnormal thyroid function Tingling, burning, numbness or weakness, possibly in arms, legs, hands and feet Vomiting
When additional side effects are noted, we will contact your study doctor to make sure these are being followed carefully.

Uncommon side effects of nivolumab include **(> 0.1% to < 1%):**
Adrenal gland function decreased Bronchitis Dehydration Diabetes Double Vision Dry eye Erythema multiforme Hair loss Heart rate increased Heart rhythm abnormal High blood pressure Hives Inflammation of the eye Inflammation of the kidney Inflammation of the pancreas Inflammation of the pituitary gland Inflammation of the stomach Inflammation of the thyroid gland Joint pain or stiffness Liver inflammation Low blood pressure Muscle inflammation Pemphigoid: blistering of the skin or mouth caused by the immune system attacking healthy tissue Pituitary gland function decreased Psoriasis: characterized by patches of abnormal, scaly skin Renal (kidney) failure or kidney injury Respiratory failure Upper respiratory tract infection Vision blurred  
  
  
Cranial nerve disorder Damage to the protective covering of the nerves in the brain and spinal cord Diabetes complications resulting in excess blood acids Disease caused by the body's immune system attacking healthy organs Drug induced liver injury Guillain-Barre syndrome, an autoimmune disorder associated with progressive muscle weakness or paralysis Inflammation of blood vessels Inflammation of the brain, potentially life-threatening or fatal Inflammation of the lining of the brain and spinal cord Inflammation of the heart Lung infiltrates, associated with infection or inflammation Myasthenic syndrome (neurologic syndrome characterized by muscle weakness) including myasthenia gravis, a nerve disease that may cause weakness of eye, face, breathing, and swallowing muscles.  
Polymyalgia rheumatica Rhabdomyolysis: muscle fiber released into the blood stream which could damage your kidneys Rosacea: acne-like skin condition resulting in redness of face Rupture of the intestine/hole in the intestine Sarcoidosis, a disease involving abnormal collections of inflammatory cells (granulomas) in organs such as lungs, skin, and lymph nodes Stevens Johnson syndrome: inflammatory disorder of skin and mucous membranes, resulting in blistering and shedding of skin Syndrome associated with fever, white blood cell activation and abnormal function
(including destruction of other blood cells by certain white blood cells), low blood cell counts, rash, and enlargement of the spleen Toxic epidermal necrolysis: a potentially fatal disease characterized by blistering and peeling of the top layer of skin resembling a severe burn Histiocytic necrotizing lymphadenitis or Kikuchi lymphadenitis: disorder of the lymph nodes which causes the lymph nodes to become enlarged, inflamed and painful, commonly affecting lymph nodes of the neck and possibly associated with fever or muscle and joint pains.  
Vogt Koyangi Harada syndrome: a disease that affects the pigmented tissue; this may affect the eye leading to swelling, pain and/or blurred vision, the ear leading to hearing loss, ringing in the ears and/or the skin leading to loss of skin color Fulminant type 1 diabetes mellitus Hepatic enzyme increased Immune-mediated nephritis Immune-mediated pneumonitis Lung Inflammation **(pneumonitis):** It is possible that nivolumab may cause inflammation of the tissues of the lung. This adverse effect has been reported in about 3% of people given nivolumab. While many people with x-ray or CT abnormalities have not developed any symptoms some people have developed mild to severe symptoms and 2 people have died as a result of their lung inflammation. Symptoms of lung inflammation may include difficulty breathing, pain or discomfort while breathing, chest pain, cough, shortness of breath, increased rate of breathing, fever, 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.  
Please inform your study doctor or nurse AT ONCE if you experience any of the following:
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.  
Any new-onset rash
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 to your overall lung symptoms, monitoring may require hospitalization. You may also be seen by a doctor called a pulmonologist, who is an expert in how your lungs work. Kidney failure: It is possible that nivolumab can cause kidney damage due to inflammation to the structures within the kidney called nephrons. This adverse event is very rare. You should let your study doctor know if you notice any decreased amount of urine, difficulty urinating, sudden weight gain, increased tiredness, increased thirst or inability to tolerate liquids. This may require treatment with steroids and holding the nivolumab.  
Opportunistic Infections due to Immunosuppression: Some subjects may require prolonged treatment with high dose corticosteroids or alternative immunosuppressants for the treatment of nivolumab related adverse events. 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 infections. 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.

Taking blood may cause discomfort, bleeding or bruising where the needle enters the body; in rare cases, it may result in fainting. There is a small risk of infection. If you feel dizzy, you should lie down for a few minutes to avoid hurting yourself if you fall.

There is the risk that information about you may become known to people outside this study. To protect against this, all study records will be identified with code numbers instead of your name. Despite the GINA protections and the best efforts of the research team, there may still be a risk if information about you were to become known to people outside of this study. CT Scans When you receive a CT scan, you will be exposed to radiation and you may be allergic to the contrast dye used during the study. The radiation exposure you will receive from participating in this study is equivalent to an exposure of 1.5 rems to your whole body (for each CT scan). The scans may also need to be repeated every 8 weeks. Naturally occurring radiation (cosmic radiation, radon, etc.) produces whole body radiation exposures of about 0.3 rem per year. Occupationally exposed individuals are permitted to receive whole body exposures of 5 rems per year.

If you agree to have a biopsy as part of this study, there are risks associated with any biopsy. The risks of the biopsy will depend on the site of the biopsy. All biopsies will be done by physicians who specialize in collecting biopsies. The risks of biopsy can include soreness and discomfort. You may feel a stinging sensation each time the biopsy needle pierces the tumor. Serious bleeding and infection are very rare, but minor bleeding is common. Tell you study doctor immediately if the bleeding is heavy or lasts a long time. Signs of infection include pain, swelling, redness, or fever. Infection is the bloodstream (sepsis), causing high fever, is rare but serious. If your lung is biopsied, there is a risk of collapsed lung. There may be side effects and discomforts that are not yet known.

Females: Azacitidine can cause harm to an embryo or fetus if given to a pregnant woman. You cannot take part in this study if you are pregnant or breast-feeding. Because of the possible risks to an embryo or fetus, if you are a female who can become pregnant, you will be asked to take a pregnancy test within 2 weeks prior to starting the study drug regimen and prior to each study drug cycle. If you decide to take part in this study, you must agree to use medical doctor-approved contraception (such as, oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) throughout the study, and for 3 months after your last dose of study drug. If you become pregnant during the study you must tell the study doctor right away. If this happens, your participation in this study will be discontinued. If you become pregnant within 3 months after taking your last dose of study drug you must tell the study doctor right away. The study sponsor will follow you and your pregnancy to birth and then for some time after birth.  
Males: If you have a partner who is able to become pregnant, you must agree to use a medical doctorapproved form of contraception throughout the study, and should avoid fathering a child for 3 months  
  
after your last dose of study drug. If your partner becomes pregnant during the study or within 3 months after you took your last dose of study drug, you must tell the study doctor right away.

You must not be pregnant or breastfeeding, and you should not become pregnant or breastfeed while you are taking the study drug. You must use an adequate method to avoid pregnancy for the duration of this study and for up to 23 weeks after the last dose of nivolumab (BMS-936558). Male subjects who are sexually active with a woman who is able to become pregnant should also use an adequate method of birth control to avoid pregnancy of their partner for up to 31 weeks after the last dose of study drug. You should immediately contact your study doctor if there is a change in your method to avoid pregnancy or if you start any prescription drug or other medication (including over-the-counter drugs and herbal supplements) not prescribed by the study doctor.

There may be unknown risks to you, your embryo or fetus, or nursing infant if you are or become pregnant during this study or are breastfeeding during this study. MRI imaging is not known to cause risk to the developing fetus though there may be risks that are not known at this time. MRI contrast is known to cross the placenta and subsequent risks to the developing fetus are not known.

Johns Hopkins does not have a program to pay you if you are hurt or have other bad results from being in the study. However, medical care at Johns Hopkins is open to you as it is to all sick or injured people.  
If you have health insurance: The costs for any treatment or hospital care you receive as the result of a study-related injury will be billed to your health insurer. Any costs that are not paid for by your health insurer will be billed to you.
If you do not have health insurance: You will be billed for the costs of any treatment or hospital care you receive as the result of a study-related injury.  
By signing this form you will not give up any rights you have to seek compensation for injury.
Clinical trial: NCT01928576
Section: Procedures
Subsections: Screening Visit:|Study Procedures:

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. If you have had some of them recently, they may not need to be repeated. This will be up to your study doctor.  
Medical history Past and current medication information will be collected A physical exam Your ability to do everyday activities will be determined Vital signs (blood pressure, heart rate, oxygenation and body temperature) will be collected Weight and height Routine blood tests (4 teaspoons) to assess your blood counts, liver, and kidney function A pregnancy test will also be done for women capable of becoming pregnant. The test will be done by collecting a urine sample or a blood sample (less than 1 teaspoon).  
MRI scan or CT scan of the brain

If the results of the "screening procedures" show that you are eligible for the study, the following procedures will be done before starting the study drugs:
CT and/or MRI scans will be done to measure the extent of your tumor.  
If the exams, tests and procedures show that you can be in the study, and you choose to take part, then you will need the following tests and procedures. They are part of regular cancer care.  
Routine blood work Periodic CT scans to assess cancer growth Tumor biopsy, if no tissue is available, is required to participate in this study Tumor biopsy prior to starting Nivolumab treatment and at the time of tumor progression is also required to participate in this study.
Clinical trial: NCT01928576
Section: Purpose of Research
Subsections: 1. What You Should Know About This Study:

You are being asked to join a research study. This consent form explains the research study and your part in it. Please read it carefully and take as much time as you need. Ask your study doctor or the study team to explain any words or information that you do not understand.  
You are a volunteer. If you join the study, you can change your mind later. There will be no penalty or loss of benefits if you decide to quit the study.  
During the study, we will tell you if we learn any new information that might affect whether you wish to continue to participate.  
If we think your participation in this study may affect your clinical care, information about your study participation will be included in your medical record, which is used throughout Johns Hopkins. Doctors outside of Johns Hopkins may not have access to this information. You can ask the research team to send this information to any of your doctors.  
When Johns Hopkins is used in this consent form, it includes The Johns Hopkins University, The Johns Hopkins Hospital, Johns Hopkins Bayview Medical Center, Howard County General Hospital, Johns Hopkins Community Physicians, Suburban Hospital, Sibley Memorial Hospital and All Children's Hospital.  
Biospecimens will be collected in this study. Biospecimens may include any of the following:
blood, tissue, saliva, urine, bone marrow, cells, etc. Most biospecimens contain DNA, which is the genetic code for each person.