Clinical trial: NCT03165721
Section: Alternatives
Subsections: What Is The Usual Approach To My Diagnosis?|What Are My Other Choices If I Do Not Take Part In This Study?

You are being asked to participate in this study because you have one of the following 3 disorders:  
Wild-type gastrointestinal stromal tumor (GIST) (this means there is no mutation in *KIT*
or PDGFRA);
Pheochromocytoma and paraganglioma (PHEO/PGL); or Kidney cancer related to a disorder called hereditary leiomyomatosis and renal cell carcinoma (HLRCC).
GIST is a type of cancer that occurs in the gastrointestinal tract (esophagus, stomach or intestines) which does not respond well to standard chemotherapy or radiation therapy. A targeted therapy used to treat most patients with GIST is called imatinib (Gleevec®), but in many children with GIST, imatinib may not work. This may be because children with this type of cancer do not have the same permanent alteration in their genes (mutation in *KIT or* PDGFRA) that is often seen in adults with the same cancer. Most GIST in pediatric patients have a deficiency in an enzyme called succinate dehydrogenase or SDH. This SDH deficiency is also seen in some patients (about 10-30%) with PHEO/PGL. The only treatment to cure PHEO/PGL is surgery, although both chemotherapy and radiation therapy are used to treat patients with PHEO/PGL. Kidney cancer in patients with HLRCC is often treated with surgery. If the cancer has metastasized outside of the kidney, the most common treatment is chemotherapy. Many patients with HLRCC have mutations in a different enzyme called FH (fumarate hydratase). SGI-110 is a small molecule that is derived from decitabine that acts as a DNA methyltransferase (DNMT) inhibitor. Its specific properties appear to work in laboratory tests in disorders that have the types of enzyme deficiencies seen in GIST, PHEO/PGL or HLRCC.

You will only be eligible for this trial if the other known treatments for your disorder, such as surgery, radiation therapy or chemotherapy, have not proven effective treatments for you. Alternatives to this experimental regimen may include partial surgical removal of your tumor, other experimental therapies, or chemotherapies you have not yet tried, or you may decide not to receive any treatment directed at shrinking your tumor(s) at this point in 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  
STUDY NUMBER: 17-C-0088 CONTINUATION: page 3 of 15 pages Please talk to your doctor about these and other options.
Clinical trial: NCT03165721
Section: Confidentiality
Subsections: Who Will See My Medical Information?

Your privacy is very important to us and the researchers will make every effort to protect it. Your information may be given out if required by law. For example, certain states require doctors to report to health boards if they find a disease like tuberculosis. However, the  
| 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   |
|--------------------------|-----------------------------------------------------------------------------------------------------------------------------|  
STUDY NUMBER: 17-C-0088 CONTINUATION: page 10 of 15 pages researchers will do their best to make sure that any information that is released will not identify you. Some of your health information, and/or information about your specimen, from this study will be kept in a central database for research. Your name or contact information will not be put in the database. There are organizations that may inspect your records. These organizations are required to make sure your information is kept private, unless required by law to provide information. Some of these organizations are:  
The study sponsor and any drug company supporting the study.  
The IRB is a group of people who review the research with the goal of protecting the people who take part in the study.  
The FDA and the National Cancer Institute in the U.S.
Your individual genomic data and health information will be put in a controlled-access database. This means that only researchers who apply for and get permission to use the information for a specific research project will be able to access the information. Your genomic data and health information will not be labeled with your name or other information that could be used to identify you. Researchers approved to access information in the database have agreed not to attempt to identify you.
Clinical trial: NCT03165721
Section: Duration of Study Involvement
Subsections: How Long Will I Be In This Study?

You will have the injections every day for 5 days, which will be repeated every 28 days as long as you do not have unacceptable side effects or your tumor(s) do not get worse. If you have side effects the dose of SGI-110 may be held for a short time and the dose may be reduced to prevent return of the side effect. Two dose reductions are allowed on this study. If the side effect(s) is too severe, or side effect(s) recur after two dose reductions, SGI-110 may need to be stopped.
Clinical trial: NCT03165721
Section: Participant's Rights
Subsections: What Are My Rights?

Taking part in this study is your choice. No matter what decision you make, and even if your decision changes, there will be no penalty to you. You will not lose medical care or any legal rights.
Clinical trial: NCT03165721
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: A Study Calendar That Shows How Often These Tests And Procedures Will Be Done Is Attached. What Possible Risks Can I Expect From Taking Part In This Study?|Common, Some May Be Serious|Occasional, Some May Be Serious In 100 People Receiving Sgi-110 (Guadecitabine), From 4 To 20 May Have:|Rare, And Serious|What Possible Benefits Can I Expect From Taking Part In This Study?|What Happens If I Am Injured Or Hurt Because I Took Part In This Study?

If you choose to take part in this study, there is a risk that the SGI-110 (guadecitabine) may not be as good as the usual approach for your cancer or condition at shrinking or stabilizing your cancer.  
You also may have the following discomforts:
Spend more time in the hospital or doctor's office. Be asked sensitive or private questions about things you normally do not discuss. May not be able to take part in future studies.
The SGI-110 (guadecitabine) used in this study may affect how different parts of your body work such as your liver, kidneys, heart, and blood. The study doctor will be testing your blood and will let you know if changes occur that may affect your health. There is also a risk that you could have side effects from the study drug/ study approach. Here are important points things to know about side effects:  
The study doctors do not know who will or will not have side effects.  
Some side effects may go away soon, some may last a long time, or some may never go away.  
Some side effects may make it hard for you to have children.  
Some side effects may be mild. Other side effects may be very serious and even result in death.
You can ask your study doctor questions about side effects at any time. Here are important ways to make side effects less of a problem:  
If you notice or feel anything different, tell your study doctor. He or she can see if it is a side effect.  
Your study doctor will work with you to treat your side effects. Your study doctor may adjust the study drugs to try to reduce side effects.
The tables below show the most common and the most serious side effects doctors know about. Keep in mind that there might be other side effects doctors do not yet know about. If important new side effects are found, the study doctor will discuss these with you.

In 100 people receiving SGI-110 (guadecitabine), more than 20 and up to 100 may have Tiredness  
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  
for  
 NIH 2514-2, Minor Patient's Assent to Participate In A Clinical Research Study STUDY NUMBER: 17-C-0088 CONTINUATION: page 7 of 15 pages Swelling and redness at the site of the medication injection Bruising, bleeding

Anemia which may require blood transfusion Infection, especially when white blood cell count is low Constipation, diarrhea, nausea, vomiting Sores in the mouth which may cause difficulty swallowing Fever Pain Loss of appetite Dizziness, headache Difficulty sleeping Shortness of breath Nose bleed Rash

In 100 people receiving SGI-110 (guadecitabine), 3 or fewer may have:  
Swelling of the eye  
Swelling of the face  
Kidney damage which may require dialysis  
You may experience diarrhea with this treatment and should record the number of stools and associated symptoms. If you develop diarrhea you should inform the study doctor. You may take a dose of loperamide after the first episode of unformed, loose stool. After discussion with the study doctor, loperamide can be continued until you are diarrhea-free for at least 12 hours. You should contact the study doctor or study nurse if you develop persistent diarrhea, diarrhea complicated by vomiting or fever, abdominal pain, or inability to take oral liquids. Reproductive Risks: You should not become pregnant or father a baby while on this study because the drugs in this study can affect an unborn baby. Women should not breastfeed a baby while on this study. It is important you understand that you need to use birth control while on  
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  
STUDY NUMBER: 17-C-0088 CONTINUATION: page 8 of 15 pages this study. Both male and female participants must use effective birth control measures while participating in this study and for at least six months after the last dose of study drug. Check with your study doctor about what kind of birth control methods to use and how long to use them. Some methods might not be approved for use in this study. Optional birth control methods include, but are not limited to, abstinence, oral birth control pills, an IUD, or condoms with spermicide. If you are a woman and become pregnant or suspect you are pregnant while participating in this study, please inform your treating physician immediately. A patient who becomes pregnant while on study drug will immediately be taken off study. Questionnaires: You will be asked to complete 2 questionnaires that take 7-12 minutes each to complete. Completion of the questionnaires may become uncomfortable for some participants, either due to boredom or due to the personal nature of the questions. Tell the health care provider if you are uncomfortable and do not wish to complete a questionnaire.

SGI-110 may cause your tumor(s) to stop growing or shrink or it may lessen the symptoms, such as pain, that are caused by the tumor. However, because there is not much information about the drug's effect on your type of tumor, we do not know if you will benefit from taking part in this study, although the knowledge gained from this study may benefit others. Your samples may be helpful to research. The researchers, using the samples from you and others, might make discoveries that could help people in the future.

If you are injured or hurt as a result of taking part in this study and need medical treatment, please tell your study doctor. Please see **Other Pertinent Information** on page 14 of 15, item 2 for more information. If you feel this injury was a result of medical error, you keep all your legal rights to receive payment for this even though you are in a study.
Clinical trial: NCT03165721
Section: Procedures
Subsections: What Extra Tests And Procedures Will I Have If I Take Part In This Study?

Most of the exams, tests, and procedures you will have are part of the usual approach for your cancer, such as physical examination, laboratory testing and scans and x-rays. However, there are some extra tests and procedures that you will need to have if you take part in this study. You will not be billed for any extra tests or procedures.
Clinical trial: NCT03165721
Section: Purpose of Research
Subsections: Why Is This Study Being Done?

The purposes of this research study are:  
1. To assess if SGI-110 is helpful in the treatment of your type of tumor(s) (causes your tumor to shrink or slow down the growth).  
2. To study how SGI-110 acts in the body (pharmacokinetics, also known as PK) in children and adults.  
3. To study the DNA methylation (the process that cells use to control gene expression) and gene expression in your tumor (the genetic instructions the tumor uses to create proteins) in response to treatment with SGI-110.
Studies in animals and other types of cancer have shown that SGI-110 can shrink tumors in some types of cancer. There are several clinical studies using SGI-110 including studies in patients with leukemia, liver cancer, ovarian cancer, melanoma, colorectal cancer and myelodysplastic syndrome (this refers to a group of bone marrow disorders in which the bone marrow does not make enough healthy blood cells). Many of these studies are ongoing. Up to 70 patients may take part in this study.
Clinical trial: NCT03165721
Section: Withdrawal from Study
Subsections: Can I Stop Taking Part In This Study?

Yes. You can decide to stop at any time. If you decide to stop for any reason, it is important to let the study doctor know as soon as possible so you can stop safely. If you stop, you can decide whether or not to let the study doctor continue to provide your medical information to the organization helping the investigator run the study. The study doctor will tell you about new information or changes in the study that may affect your health or your willingness to continue in the study. The study doctor may take you out of the study:  
If your health changes and the study is no longer in your best interest If new information becomes available If you do not follow the study rules If the study is stopped by the sponsor, IRB (the Institutional Review Board) or FDA (U.S.  
Food and Drug Administration). The sponsor is the company or organization, in this study it is Cancer Therapy Evaluation Program or CTEP, that is responsible for  
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  
for NIH 2514-2, Minor Patient's Assent to Participate In A Clinical Research Study  
STUDY NUMBER: 17-C-0088 CONTINUATION: page 9 of 15 pages overseeing the study. CTEP works with the drug company making SGI-110 and makes it available for this study.