Clinical trial: NCT01853618
Section: Alternatives
Subsections: Alternative Approaches Or Treatments

What other choices do I have if I do not take part in this study? Instead of being in this study, you have these options:  
x Getting treatment or care for your cancer without being in a study x Taking part in another study  
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:13-C-0120 CONTINUATION: page 8 of 12 pages  
x 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. Instead, it tries to improve how you feel. Comfort care tries to keep you as active and comfortable as possible.
Please talk to your doctor about these and other options.
Clinical trial: NCT01853618
Section: Confidentiality
Subsections: Will Your 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. Organizations that may look at and/or copy your medical records for research, quality assurance, and data analysis include:  
x The National Cancer Institute (NCI) and other government agencies, like the Food and Drug Administration (FDA), which are involved in keeping research safe for people.  
x National Cancer Institute Institutional Review Board.  
x Qualified representatives from MedImmune, Inc., the pharmaceutical company who produces Tremelimumab.
Clinical trial: NCT01853618
Section: Duration of Study Involvement
Subsections: During The Study|When You Are Finished Taking The Drugs (Treatment)|This Consent Document Has Been Approved For Use From June 10, 2019 Through June 24, 2020.

If the exams, tests and procedures show that you can be in the study, and you choose to take part, then you will begin treatment. Treatment involves receiving Tremelimumab through a vein (IV) once every 4 weeks and then once every 12 weeks for 2 years' total. Treatment can be stopped before completion of 2 years' therapy if your disease shows clear evidence of growth or your body is no longer tolerating the treatment. A 4-week time-period is called a cycle. In this study, there are six initial cycles followed by maintenance. On the first day of every cycle you will receive the following:
x History and physical exam  
x Review of current medications and treatments x Routine and research blood tests. The purposes of the research blood tests will be to see if there is evidence that your immune system has become 'activated' by the treatment.  
x Urine laboratory tests x Receive Tremelimumab On the first day of every week during cycles 1 through 6 you will receive the following:
x Routine blood tests x History and physical exam x Review of current medications and treatments
During your second cycle (within 4 days of Day 36), you will receive the TACE, RFA, SBRT or cryoablation procedure. The procedure that you will receive at this time is based on the size and location of your tumor as well as other conditions that will be discussed by the study doctors. Every 8 weeks, you will have tumor measurements using special x-rays called computerized tomography (CT or CAT scans) or magnetic resonance imaging (MRI) of your chest, stomach, and pelvis. While you are in the maintenance phase of the study if it is confirmed that your disease has progressed you may be eligible to receive re-induction therapy using Tremelimumab. This option will be discussed with you by your study doctor.  
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:13-C-0120 CONTINUATION: page 4 of 12 pages

After you have finished taking the study drugs, you will be asked to return to clinic within 4 weeks for a safety follow up visit. At this visit, you will be asked questions about your health, get a physical exam and undergo routine and research blood and urine tests. If you have any unresolved drug related health issues, you will be followed until you feel better. If you are unable to return for this visits, we will obtain the information from you by telephone. After that we will contact you by phone once a year.

Signature of Investigator Date Signature of Witness Date Print Name Print Name 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
Clinical trial: NCT01853618
Section: Participant's Rights
Subsections: Research Subject'S Rights What Are The Costs Of Taking Part In This Study?

If you choose to take part in the study, the following will apply, in keeping with the NIH policy:
x You will receive study treatment at no charge to you. This may include surgery, medicines, laboratory testing, x-rays or scans done at the Clinical Center, National Institutes of Health (NIH), or arranged for you by the research team to be done outside the Clinical Center, NIH if the study related treatment is not available at the NIH.  
x There are limited funds available to cover the cost of some tests and procedures performed outside the Clinical Center, NIH. You may have to pay for these costs if they are not covered by your insurance company.  
x Medicines that are not part of the study treatment will not be provided or paid for by the Clinical Center, NIH.  
x Once you have completed taking part in the study, medical care will no longer be provided by the Clinical Center, NIH.
Clinical trial: NCT01853618
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Risks Or Discomforts Of Participation|Risks From Study Therapy All Participants Tremelimumab:|Risks From Blood Collection|Risks From Biopsy|Potential Benefits Of Participation Are There Benefits To Taking Part In This Study?

If you choose to take part in this study, there is a risk that:  
x You may lose time at work or home and spend more time in the hospital or doctor's office than usual x You may be asked sensitive or private questions which you normally do not discuss.
There is also a risk that you could have side effects from the study drug. Here are important points about side effects:  
x The study doctors do not know who will or will not have side effects.  
x Some side effects may go away soon, some may last a long time, or some may never go away.  
x Some side effects may interfere with your ability to have children.  
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:13-C-0120 CONTINUATION: page 5 of 12 pages Here are important points about how you and the study doctor can make side effects less of a problem:
x Tell the study doctor if you notice or feel anything different so they can see if you are having any symptoms.  
x The study doctor may be able to treat some side effects.  
Below we 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.

The following are side effects that have been associated with Tremelimumab:  
x Diarrhea x Rash x Pruritus (itching)
x Fatigue x Nausea x Vomiting x Anorexia (loss of appetite) x Headache x Abdominal Pain x Auto-immune changes to the pituitary gland leading to hormonal changes.  
x Inflammation of the part of the intestine known as the colon which can lead to infection, blood in the stools and abdominal pain. This is also known as 'colitis'. Colitis has the potential to be life threatening and require prolonged hospitalizations. As part of its management it may require treatment with steroids which may place you at increased risk for severe infections.  
x Inflammation of the liver which is also known as hepatitis. In extreme cases this may result in liver failure and death.  
x Occasionally you can also get a skin rash related to the treatment and this can also result in severe and life threatening symptoms.  
x Problems related to Tremelimumab infusion x There is a remote chance that you may have a serious allergic reaction (anaphylaxis) to Tremelimumab. Anaphylaxis may cause a serious drop in blood pressure, difficulty in breathing, severe hives, and sometimes death. Your doctor will monitor you very closely after you receive the Tremelimumab, and will have medications available to treat any  
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:13-C-0120 CONTINUATION: page 6 of 12 pages  
allergic reactions that might occur. Less serious allergic reactions, such as skin rash with or without itching and swelling, may also occur within hours to days after receiving the Tremelimumab. These effects usually get better without treatment.  
x There is a remote chance that you may develop new allergies to previously exposed substances, other than Tremelimumab. For example, it is possible that you could develop an allergy to shellfish or IV contrast while taking Tremelimumab. These allergies may be severe and life threatening.

Side effects of blood draws include pain and bruising in the area where the needle was placed, lightheadedness, and rarely, fainting. When large amounts of blood are collected, low red blood cell count (anemia) can develop.

This procedure usually causes only brief discomfort at the site from which the biopsy is taken. Rarely, infection or bleeding may occur at the needle site. Tumor biopsies will be done by a specialist using the CT scanner or ultrasound machine to guide the biopsy needle into the tumor to ensure accuracy. To collect the research biopsies, you will be exposed to 3 CT scans. This radiation exposure is not required for your medical care and is for research purposes only. The amount of radiation you will receive in this procedure is 2.3 rem which is below the guideline of 5 rem per year allowed for research subjects by the NIH Radiation Safety Committee. The average person in the United States receives a radiation exposure of 0.3 rem per year from natural sources, such as the sun, outer space, and the earth's air and soil. If you would like more information about radiation, please ask the investigator for a copy of the pamphlet, An Introduction to Radiation for NIH Research Subjects.  
| TACE Procedure (Cohort A/B)  Likely   | Less Likely                                                                                                                   | Rare but Serious   |                                    |
|---------------------------------------|-------------------------------------------------------------------------------------------------------------------------------|--------------------|------------------------------------|
| x                                     | Abdominal pain                                                                                                                |                    |                                    |
| x                                     | Fever                                                                                                                         |                    |                                    |
| x                                     | Nausea and/or vomiting                                                                                                        | x                  | Abdominal fluid buildup  (Ascites) |
| x                                     | Bleeding (at catheter  insertion site)                                                                                        |                    |                                    |
| x                                     | Allergy to iodine contrast  agent                                                                                             | x                  | Liver failure                      |
| x                                     | Kidney failure                                                                                                                |                    |                                    |
| x                                     | Liver abscess formation                                                                                                       |                    |                                    |
| x                                     | Stomach or duodenal ulcer                                                                                                     |                    |                                    |
| x                                     | Pancreatitis                                                                                                                  |                    |                                    |
| x                                     | Cholecystitis (irritation of  the gall bladder)                                                                               |                    |                                    |
| x                                     | Arterial injury at catheter  insertion site                                                                                   |                    |                                    |
| 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:13-C-0120 CONTINUATION: page 7 of 12 pages RFA Procedure (Cohorts A/B/E) The risks from the radiofrequency or microwave ablation procedure itself include a small chance of bleeding, injury to the normal liver tissue, and re-growth of the tumor. An infection, called an abscess, can develop in the treated tumor, and may require antibiotics and/or putting a temporary tube in the abscess to drain it. There should be minimal discomfort from the ablation procedure itself during the ablation procedure, because you will be "asleep" under general anesthesia. The length of time you will need to be in the hospital will vary but will be estimated by your doctors. This will be discussed with you in greater detail prior to the procedure.

The aim of this study is to see if this experimental treatment will cause your tumors to shrink. 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.
Clinical trial: NCT01853618
Section: Procedures
Subsections: Description Of Research Study Before You Begin The Study

Before you begin this study, you will have several exams and tests to make sure you are eligible for this study. The exams and tests are part of regular cancer care and may be done even if you do not join the study. If you recently had some of the tests, they may not need to be repeated. The research team will explain these exams and tests to you. You will have:  
x History and physical exam x Review of current medications and past treatments x Blood work x Urine laboratory tests
x Tumor measurements using special x-rays called computerized tomography (CT or CAT
scans) or magnetic resonance imaging (MRI) of your chest, stomach, and pelvis areas  
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:13-C-0120 CONTINUATION: page 3 of 12 pages x A heart test called an electrocardiogram or ECG to check your heart  
x Urine or blood pregnancy test
Clinical trial: NCT01853618
Section: Purpose of Research
Subsections: Why Is This Study Being Done?|Why Are You Being Asked To Take Part In This Study?

This research is being done to study the effectiveness of the combination of the drug Tremelimumab with trans-arterial catheter chemoembolization (TACE), radiofrequency ablation (RFA) or cryoablation. Tremelimumab is an experimental drug that has not been approved by the U.S. Food and Drug Administration (FDA). TACE, RFA and cryoablation are standard procedures that are used to treat tumors.  
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:13-C-0120 CONTINUATION: page 2 of 12 pages If you receive TACE a small catheter will be placed into the artery at the groin and chemotherapy will be injected directly into the liver. A material which closes off the vessels supplying blood to the tumor is also injected. If you receive RFA you will be put to sleep and a needle will directly be placed into the tumor and your tumor will be burnt (or part of it). If you receive Cryoablation you will be put to sleep and a needle will be put directly into the tumor and the tumor will be frozen (or part of it). Once it is determined which procedure you will receive your doctor will explain the procedure in full detail. Although Tremelimumab is not approved by the FDA, it has been evaluated in a number of clinical studies, and over 1000 patients, most of whom had melanoma. Tremelimumab is similar in how it works to another drug (called ipilimumab) which was recently approved by the FDA. Tremelimumab has been tested in a small group of patients with liver cancer or hepatocellular cancer (HCC) and in general was well tolerated. It has not been tested however in combination with TACE, RFA or cryoablation, which is the main goal of this study.

You are being asked to take part in this study because you have advanced hepatocellular cancer (HCC) or biliary tract cancer that has not responded to other types of therapy, and your doctor has determined that you are not a candidate for liver transplantation.
Clinical trial: NCT01853618
Section: Withdrawal from Study
Subsections: Stopping Therapy

Your doctor may decide to stop your therapy for the following reasons:
x if he/she believes that it is in your best interest  
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:13-C-0120 CONTINUATION: page 9 of 12 pages  
x if your disease comes back during treatment x if you have side effects from the treatment that your doctor thinks are too severe x if new information shows that another treatment would be better for you x if you become pregnant
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 MedImmune, Inc. 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.