Clinical trial: NCT01273155
Section: Alternatives
Subsections: Alternative Approaches Or Treatments What Other Choices Do I Have If I Do Not Take Part In This Study?

Talk to your doctor about your choices before you decide if you will take part in this study. Your other choices may include:  
- Getting treatment or care for your cancer without being in a study.  
- Taking part in another study. However, if you have moderate or severe abnormal liver function, you may not be eligible for most other studies.  
- Getting comfort care, also called palliative care. This kind of care helps reduce pain, tiredness, appetite problems, and other problems caused by 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.
Clinical trial: NCT01273155
Section: Confidentiality
Subsections: Will My 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. Your personal information may be given out if required by law. If information from this study is published or presented at scientific meetings, your name and other personal information will not be used. Organizations that may look at and/or copy your medical records, including research 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), involved in keeping research safe for people
- Qualified representatives from the maker of belinostat.  
- Member institutions of the NCI Organ Dysfunction Working Group and their associated scientific review and Institutional Review Boards
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.
Clinical trial: NCT01273155
Section: Duration of Study Involvement
Subsections: During The Study

After you are accepted for this study and you choose to take part, you will begin taking the study drug, belinostat. Belinostat is given through a vein for 30 minutes. Belinostat will be given in cycles. Except for cycle 1, all cycles are 3 weeks long. Cycle 1 is 4 weeks long. Now, we will  
PATIENT IDENTIFICATION CONSENT TO PARTICIPATE IN A CLINICAL  
RESEARCH STUDY (Continuation Sheet)  
- Adult Patient or - Parent, for Minor Patient  
NIH-2514-1 (07-09) P.A.: 09-25-0099 File in Section 4: Protocol Consent  
STUDY NUMBER: 11-C-0060 CONTINUATION: page 3 of 13 pages describe what will happen during each cycle. For cycle 1 only, you will receive one extra dose of belinostat 1 week before the regular treatment starts (Day -7). **In each cycle,** belinostat will be given once a day for 5 days (Day 1-5). For some study procedures we will need you to come to the Clinical Center. You will also have tests performed because you are in the study to see how the study drugs are affecting your body. This will include imaging studies (for example, CT scans) every 2 cycles (about every 6 weeks) to find out if your cancer has responded. Clinical Center Visits: We will ask that you come to the Clinical Center each day you receive belinostat (6 days in cycle 1 and 5 days in all other cycles) (see Study Chart). While you are at the Clinical Center, we will also perform study tests and procedures to see how the study drugs are affecting your body. Standard procedures being done because you are in this study; these may be done more
Clinical trial: NCT01273155
Section: Participant Responsibilities
Subsections: - **Complete Medical History.**

- **Physical examination,** including height, weight, blood pressure, pulse, and temperature.  
- **Standard blood tests** (requiring about 1 tablespoon of blood total), which include measurement of your white blood cells, red blood cells, platelets, blood sugar and electrolytes, how your liver and kidneys work, and how well your blood clots.  
- **Urine tests:** Depending on the results of blood tests, you may be asked to give a collect your urine for 24 hours for further testing.  
- **Pregnancy test:** A blood test will be done to check for pregnancy in women who are able to become pregnant.  
- EKG to check your heart.  
- **CT scans** of your chest, abdomen, and pelvis to measure your tumor(s). Other imaging tests may be done as needed.
Clinical trial: NCT01273155
Section: Participant's Rights
Subsections: Research Subject'S Rights What Are My Rights If I Take Part In This Study?|Research Subject'S Rights

Taking part in this study is your choice. You may choose either to take part or not to take part in this study. If you decide to participate, 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 if you are eligible and choose to participate in another trial. We will tell you about new information or changes in the study that may affect your health or your willingness to continue in the study. 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.

Taking part in this research study is voluntary, and you can withdraw at any time. We encourage you to ask questions so you can make the most informed decisions while you take part in this study. Refusal to take part will not result in penalty or loss of benefits to which you are otherwise entitled. It is important to stress that being in this study does not promise long-term medical care here at the NIH Clinical Center. If there is no further research study that is suitable for you and your state of disease, or if you are not now on another research study, you will be returned to the care of your referring doctor or institution or other source of care closer to your home. If you have any questions about your treatment at NIH, you can contact the Principal Investigator, Dr. Alice Chen (301-496-4291) or the patient care representative (301-496-2626).
Clinical trial: NCT01273155
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Often Because You Are In The Study:|Risks Or Discomforts Of Taking Part What Side Effects Or Risks Can I Expect From Being In This Study?|Occasional, Some May Be Serious|Side Effects Of Blood Draw:|Potential Benefits Of Taking Part Are There Benefits To Taking Part In This Study?

- **Clinic visit** to ask how you are feeling and to evaluate you with a physical examination at the beginning of each cycle.  
- **Vital signs:** You will need to have your vital signs, including your temperature, heart rate, blood pressure, and respiratory rate, measured each time you are seen in the outpatient clinic.  
- **Blood tests:** Measurement of your white blood cells, red blood cells and platelets, and measurements of your blood sugar and electrolytes and of how your liver and kidneys work will be done each time you are seen in the outpatient clinic. All of these blood tests combined will require 1-2 tablespoons (20-30 mL) of blood each time.  
- **Urine test:** Depending on the results of blood tests, you may be asked to give a urine sample for testing or to collect your urine for 24 hours for further testing.  
- EKG to check your heart on Day 5 of cycle 1, at the beginning of cycle 2, and more often if needed.  
- **CT scans** or other imaging tests such as ultrasound (an examination using sound waves) or MRI (an examination using magnetic field and radio waves) that detect your tumor will be done every 2 cycles (about every 6 weeks) while you are receiving treatment. This is done so that any benefit of the treatment can be determined, and so that if your cancer is not responding to the treatment, the study team can tell you and help you move to a different treatment program (discussed further below).  
Tests and procedures that are either being tested in this study or being done to see how the study is affecting your body:
- **Measurements of the drug in your blood:** We will collect blood samples to measure amounts of belinostat in your blood several times during cycle 1. Because we will collect several blood draws, a thin, flexible plastic tube (called a "catheter") will be placed in your arm, and all blood samples would be taken from this tube. Using a catheter will reduce the PATIENT IDENTIFICATION CONSENT TO PARTICIPATE IN A CLINICAL
RESEARCH STUDY (Continuation Sheet)
- Adult Patient or - Parent, for Minor Patient NIH-2514-1 (07-09) P.A.: 09-25-0099 File in Section 4: Protocol Consent STUDY NUMBER: 11-C-0060 CONTINUATION: page 4 of 13 pages number of times a needle would be placed in your vein. The total amount of blood that we collect will be about 4 tablespoons (52 mL).  
Patients in this study will be divided into 4 groups. You will be placed in one of these groups based on how your liver is functioning (determined from the results of the blood tests done to check your liver). Up to 12 patients with normal liver function will be included in the study. All of the patients with normal liver function will receive the same dose of belinostat. For each group of patients with abnormal liver function, 3 patients will be enrolled and will begin with a low dose of belinostat. If no serious side effects are reported, the next set of 3 patients enrolled in that group will receive a higher dose of belinostat. This will continue as long as belinostat is well tolerated, or the dose reaches the level that caused side effects in patients with normal liver function. The dose level of the study drug you receive will depend on when you enter the study, and whether patients enrolled before you had any serious side effects at their dose levels. If serious side effects are seen, the dose of the study drug may be lowered or stopped depending on the severity of the side effects.

If you choose to take part in this study, there is a risk that you may:
- Lose time at work or home and spend more time in the hospital or doctor's office than usual
- Be asked sensitive or private questions which you normally do not discuss The agents 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(s)/study approach. Here are important points 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 interfere with your ability to have children.  
- Some side effects may be serious and may even result in death.  
Here are important points about how you and the study doctor can make side effects less of a problem:
- Tell the study doctor if you notice or feel anything different so they can see if you are having a side effect.  
- The study doctor may be able to treat some side effects.  
- The 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 that researchers know about. There might be other side effects that researchers do not yet know about. If important new side effects are found, the study doctor will discuss these with you.  
STUDY NUMBER: 11-C-0060 CONTINUATION: page 6 of 13 pages It is important to remember that this is a dose-ranging study, meaning that the dose of belinostat will increase between groups of patients until notable side effects are seen. Because of this, some patients may have severe side effects as the study investigators find the highest dose of belinostat can be given safely to patients with different degrees of liver function. We already know the "safe dose" for patients with normal liver function and will not give you a dose bigger than this. If a dose has too many or certain unacceptable side effects, a lower dose may be recommended as the "safe dose" for future testing in patients with abnormal liver function. Risks and side effects observed with **belinostat** include:

In 100 people receiving belinostat, from 4 to 20 may have:
- Anemia which may require blood transfusion
- Belly pain
- Constipation
- Dry mouth
- Swelling of arms, legs
- Fever
- Swelling and redness at the site of the medication injection
- Infection
- Change in the heart rhythm
- Bruising, bleeding
- Weight loss, loss of appetite
- Dehydration - Dizziness, headache
- Changes in taste
- Shortness of breath
- Rash
- Flushing STUDY NUMBER: 11-C-0060 CONTINUATION: page 7 of 13 pages

Infrequent (occurs in 1 to 10 out of 100 people): persistent pain and discomfort at the injection or needle insertion site as well as possible infection, bleeding, bruising, and soreness.  
Reproductive Risks: Because the effect of Belinostat on unborn babies is not known, you should not become pregnant or father a baby while on this study. Women of childbearing potential will be required to have a pregnancy test. If you are a woman who is breast feeding or pregnant, you may not participate in the study because we don't know how this medicine would affect your baby or your unborn child. If you are a woman who can become pregnant, or are the partner of a woman who can become pregnant, you will need to practice an effective form of birth control before starting study treatment, during study treatment, and for 3 months after you finish study treatment. If you think that you or your partner is pregnant, you should tell your study doctor or nurse at once. Avoiding sexual activity is the only certain method to prevent pregnancy. But, if you choose to be sexually active, you should use an appropriate "double barrier" method of birth control (such as female use of a diaphragm, intrauterine device (IUD), or contraceptive sponge, in addition to male use of a condom) or the female should be using prescribed "birth control" pills, injections, or implants. Male participants must also use adequate contraception. If you choose to be sexually active during this study, you understand that even with use of these birth control measures, pregnancy could still result. Some methods might not be approved for use in this study. Ask about counseling and more information about preventing pregnancy. Belinostat may reduce a man's ability to father a child or a woman's ability to become pregnant, and in some cases this may be permanent. Women should not breast feed during the study and for 30 days after finishing study treatment. For more information about risks and side effects, ask your study team.

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.  
STUDY NUMBER: 11-C-0060 CONTINUATION: page 8 of 13 pages
Clinical trial: NCT01273155
Section: Procedures
Subsections: What Will Happen If I Take Part In This Study? Before You Begin The Study

You will need to have the following examinations, tests, or procedures to find out if you can be in the study. These examinations, tests, or procedures are part of your regular cancer care and should be done by your health care team even if you do not join the study. If you have had them recently, they may not need to be repeated. This will be up to your study doctor. If you decide that you would like to participate in this study, you will be asked to sign this consent form. You will then have the examinations, tests, and procedures listed below done to see if you can take part in the study (this is called the screening/baseline evaluation).
Clinical trial: NCT01273155
Section: Purpose of Research
Subsections: Description Of Research Study

The purpose of this study is to test the safety of belinostat at different dose levels in patients with cancer who have different degrees of liver function. Belinostat is an experimental drug that works by helping to turn on genes that control cell growth and survival that are switched off in cancer cells. This is the first study in which belinostat will be given to patients with different degrees of liver function. We already know the safe dose for patients with normal liver function. Other purposes of this study are to find out what side effects occur when belinostat is given to patients with different degrees of liver function, how much belinostat is in your blood at specific times, and whether or not belinostat is effective in treating your cancer. We will compare how the patients  
PATIENT IDENTIFICATION CONSENT TO PARTICIPATE IN A CLINICAL  
RESEARCH STUDY  
- Adult Patient or - Parent, for Minor Patient NIH-2514-1 (07-09) P.A.: 09-25-0099  
File in Section 4: Protocol Consent (1)  
STUDY NUMBER: 11-C-0060 CONTINUATION: page 2 of 13 pages with abnormal liver function do in comparison with patients with normal liver function. That is the reason that a group of patients with normal liver function will also be included on this trial.
Clinical trial: NCT01273155
Section: Withdrawal from Study
Subsections: Stopping Therapy

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 gets worse 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
- if too many patients in the study experience severe side effects
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 the Cancer Therapy Evaluation Program (CTEP) at the National Cancer Institute (NCI) 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.  
STUDY NUMBER: 11-C-0060 CONTINUATION: page 10 of 13 pages