Clinical trial NCT02821754
Conditions: Biliary Tract Neoplasms Liver Cancer Hepatocellular Carcinoma Cholangiocarcinoma Bile Duct Cancer
Keywords: PDL1-Mediated Adaptive Resistance Monoclonal Antibody CTLA-4 Ablative Therapy Combination of Tremelimumab and Durvalumab
Sponsor: National Cancer Institute (NCI)
Start date: 2016-07-05; Completion date: 2022-12-31
Enrollment: 54 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
BACKGROUND:

* Various tumor ablative procedures and techniques have been shown to result in immunogenic cell death and induction of a peripheral immune response. The term ablative therapies applies to trans-arterial catheter chemoembolization (TACE), radiofrequency ablation (RFA) and cryoablation (CA).
* The underlying hypothesis of this study is that the effect of immune checkpoint inhibition can be enhanced by TACE, CA and RFA in patients with advanced hepatocellular carcinoma (HCC) and biliary tract carcinomas (BTC). We have already demonstrated proof of principle as well as safety and feasibility of this approach with anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) therapy.
* Based on the concept of programmed death-ligand 1 (PDL1)-mediated adaptive resistance and the emerging role of programmed cell death protein 1 (PD1) therapy in HCC, we would like to evaluate the combination of tremelimumab and durvalumab (with ablative therapies) in HCC and BTC.

Objectives:

\- To preliminarily evaluate the 6-month progression free survival (PFS) of combining tremelimumab and durvalumab in patients with advanced HCC (either alone or with cryoablation, TACE or RFA) and in patients with advanced biliary tract carcinoma (BTC) (either alone or with cryoablation or RFA).

ELIGIBILITY:

* Histologically or cytologically confirmed diagnosis of HCC or biliary tract carcinoma OR histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of HCC (or biliary tract carcinoma).
* Childs-Pugh A/B7 cirrhosis only is allowed. If patient does not have cirrhosis, this limitation does not apply.
* Patients must have disease that is not amenable to potentially curative resection, radiofrequency ablation, or liver transplantation.

DESIGN:

We will evaluate the combination of tremelimumab and durvalumab (with ablative therapies) in cohorts A (HCC; N=40) and B (BTC; N=30). The first N=10 patients in both cohorts will receive tremelimumab and durvalumab only (i.e. No interventional radiologic procedures).

* A: Advanced HCC, BCLC# Stage B/C

  * N= 1st 10 pts: No ablative procedure Cryoablation/RFA/TACE##
  * Tremelimumab 75mg flat dose every (q)28 days for 4 doses; Durvalumab 1500mg flat dose q28 days until end of study (EOS)###
  * 40 total: 10 trem+ dur alone; 10 trem+ dur + TACE; 10 trem + dur + RFA; 10 trem + dur + cryo
* B: Intra/extra-hepatic cholangiocarcinoma

  * N= 1st 10 patients (pts): No ablative procedure; RFA/ cryoablation
  * Tremelimumab 75mg flat dose q28 days for 4 doses; Durvalumab 1500mg flat dose q28 days until EOS###
  * 30 total: 10 trem+ dur alone; 10 trem + dur + RFA; 10 trem

    * BCLC = Barcelona clinic liver cancer staging system

      * For BCLC stage B patients TACE may be repeated as per standard of care

        * EOS = End of study treatment or meeting any of the off-treatment or off study criteria.

Detailed description:
BACKGROUND:

* Various tumor ablative procedures and techniques have been shown to result in immunogenic cell death and induction of a peripheral immune response. The term ablative therapies applies to trans-arterial catheter chemoembolization (TACE), radiofrequency ablation (RFA) and cryoablation (CA).
* The underlying hypothesis of this study is that the effect of immune checkpoint inhibition can be enhanced by TACE, CA and RFA in patients with advanced hepatocellular carcinoma (HCC) and biliary tract carcinomas (BTC). We have already demonstrated proof of principle as well as safety and feasibility of this approach with anti-CTLA4 therapy.
* Based on the concept of PDL1-mediated adaptive resistance and the emerging role of PD1 therapy in HCC, we would like to evaluate the combination of tremelimumab and durvalumab (with ablative therapies) in HCC and BTC.

Objectives:

\- To preliminarily evaluate the 6-month progression free survival (PFS) of combining tremelimumab and durvalumab in patients with advanced HCC (either alone or with cryoablation, TACE or RFA) and in patients with advanced biliary tract carcinoma (BTC) (either alone or with cryoablation or RFA).

ELIGIBILITY:

* Histologically or cytologically confirmed diagnosis of HCC or biliary tract carcinoma OR histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of HCC (or biliary tract carcinoma).
* Childs-Pugh A/B7 cirrhosis only is allowed. If patient does not have cirrhosis, this limitation does not apply.
* Patients must have disease that is not amenable to potentially curative resection, radiofrequency ablation, or liver transplantation.

DESIGN:

We will evaluate the combination of tremelimumab and durvalumab (with ablative therapies) in cohorts A1 (HCC; Barcelona clinic liver cancer staging system (BCLC) stage C; N=10), A2 (HCC; BCLC stages B/C; N=30) and B (BTC; N=30). The patients in cohort A1 and first 10 patients in cohort B will receive tremelimumab and durvalumab only (i.e. no interventional radiologic procedures).

Arms: arm 1: Durvalumab + Tremelimumab arm 2: Durvalumab + Tremelimumab + TACE arm 3: Durvalumab + Tremelimumab+ RFA arm 4: Durvalumab + Tremelimumab+ Cryoablation
Interventions: intervention 1: Durvalumab intervention 2: Tremelimumab intervention 3: Trans-arterial Catheter Chemoembolization (TACE) intervention 4: Radiofrequency Ablation (RFA) intervention 5: Cryoablation
Intervention descriptions: intervention 1: Flat dose of 1500 mg every 4 weeks. intervention 2: Flat dose of 75 mg every 4 weeks for up to 4 doses. intervention 3: TACE will be performed on Day 36 (+/-96hrs). intervention 4: RFA will be performed on Day 36 (+/-96hrs). intervention 5: Cryoablation will be performed on Day 36 (+/-96hrs).

Protocol documents:
ICF_002.pdf: 
MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
INSTITUTE: 
National Cancer Institute 
STUDY NUMBER: 
16-C-0135 
PRINCIPAL INVESTIGATOR: 
Tim Greten, M.D. 
STUDY TITLE:  
A Pilot Study of Combined Immune Checkpoint Inhibition in Combination with 
Ablative Therapies in Subjects with Hepatocellular Carcinoma (HCC) or Biliary Tract 
Carcinomas (BTC) 
 
Continuing Review Approved by the IRB on 05/08/17 
Amendment Approved by the IRB on 06/26/17 (C) 
 
Date posted to web:  07/18/17 
Drug Only 
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) 
 
 
INTRODUCTION 
We invite you to take part in a research study at the National Institutes of Health (NIH). 
First, we want you to know that: 
Taking part in NIH research is entirely voluntary.  
You may choose not to take part, or you may withdraw from the study at any time.  In 
either case, you will not lose any benefits to which you are otherwise entitled.  However, 
to receive care at the NIH, you must be taking part in a study or be under evaluation for 
study participation. 
You may receive no benefit from taking part.  The research may give us knowledge that 
may help people in the future. 
Second, some people have personal, religious or ethical beliefs that may limit the kinds of 
medical or research treatments they would want to receive (such as blood transfusions).  If you 
have such beliefs, please discuss them with your NIH doctors or research team before you agree 
to the study. 
Now we will describe this research study.  Before you decide to take part, please take as much 
time as you need to ask any questions and discuss this study with anyone at NIH, or with family, 
friends or your personal physician or other health professional.   
Why is this study being done?  
This research is being done to study the safety and effectiveness of the combination of 
durvalumab (formerly known as MEDI4736) and tremelimumab with and without trans-arterial 
catheter chemoembolization (TACE), radiofrequency ablation (RFA), or cryoablation. 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:  16-C-0135 
CONTINUATION: page 2 of 15 pages 
 
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 
 
As you are among the first group of ~ 20 subjects enrolling on the study, you will be assigned to 
take durvalumab and tremelimumab. The second group of 50 subjects will be will be assigned to 
take durvalumab and tremelimumab with TACE, RFA or cryoablation. 
Tremelimumab is an experimental drug that has not been approved by the U.S. Food and Drug 
Administration (FDA). 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.  
Durvalumab is an investigational drug designed to boost the body’s immune system by targeting 
a protein on tumor cells called PDL-1. PDL-1 normally maintains the balance of the immune 
system. In cancer, PDL-1 helps tumors evade detection and elimination by the immune system. 
Durvalumab may increase the immune system’s ability to identify and destroy cancer cells. 
“Investigational” means that durvalumab has not been approved by the Food and Drug 
Administration (FDA) as either a prescription or over-the-counter drug.  
TACE, RFA, and cryoablation are standard procedures that are used to treat tumors. 
This is the first study in which both drugs taken together will be tested in combination with 
TACE, RFA, or cryoablation, which is the main goal of this study. 
Why are you being asked to take part in 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. 
How many people will take part in this study?  
About 90 people will take part in this study. 
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: 
• Confirmation of diagnosis (You must provide a sample tumor tissue for an NCI lab to 
evaluate.  The tissue may be from a previous surgery or biopsy.  If none is available, we 
will ask you to undergo a biopsy to provide a fresh sample.) 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:  16-C-0135 
CONTINUATION: page 3 of 15 pages 
 
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 
 
• History and physical exam 
• Review of current medications and past treatments 
• Blood work 
• Urine laboratory tests 
• 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 
• A heart test called an electrocardiogram or ECG to check your heart 
• Urine or blood pregnancy test 
During the study 
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.  
Before you begin treatment, you will have a biopsy of your tumor using a needle. 
In this study, study therapy will be divided into cycles, each lasting 28 days. Treatment involves 
receiving tremelimumab and durvalumab through an IV on day 1 of each cycle. You will be 
asked to undergo optional tumor biopsies during cycle 2 on day 8 (day 36) and after you have 
completed the third cycle (day 85) of tremelimumab and durvalumab. You will receive 
tremelimumab for up to 4 cycles.  You will continue to receive durvalumab until your disease 
worsens, you experience intolerable side effects or you have completed 12 months of study 
therapy, whichever comes first.  
When you are finished taking the drugs (treatment) 
You will be seen within 60 days after completion of the study treatment to assess for possible 
delayed or ongoing side effects and overall clinical status. At this visit, you will have basic blood 
tests as well as blood collected for research purposes. 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:  16-C-0135 
CONTINUATION: page 4 of 15 pages 
 
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 Calendar 
Cycle 1 
Day 1 
• History and physical exam 
• Review of current medications and treatments 
• Routine and research blood tests 
• Research rectal swab* 
• Tumor biopsy 
• Tremelimumab infusion 
• Durvalumab infusion 
Day 8 
• Routine and research blood tests 
Day 15 
• Routine and research blood tests 
Day 22 
• Routine blood tests 
Cycle 2 
Day 1 
• History and physical exam 
• Review of current medications and treatments 
• Routine and research blood tests 
• Research rectal swab* 
• Tremelimumab infusion 
• Durvalumab infusion 
Day 8  
(Day 36) 
• Routine and research blood tests 
• Tumor biopsy (optional) 
Day 15 
• Routine blood tests 
Day 22 
• Routine blood tests 
Cycle 3 
Day 1 
• History and physical exam 
• Review of current medications and treatments 
• Routine and research blood tests 
• Tremelimumab infusion 
• Durvalumab infusion  
• CT Scan or MRI 
Day 8 
• Routine and research blood tests 
Day 15 
• Routine blood tests 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:  16-C-0135 
CONTINUATION: page 5 of 15 pages 
 
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 
 
Day 22 
• Routine blood tests 
Cycle 4 
Day 1 
(Day 85) 
• History and physical exam 
• Review of current medications and treatments 
• Routine and research blood tests 
• Research rectal swab*  
• Tumor Biopsy (optional) 
• Tremelimumab infusion 
• Durvalumab infusion  
Day 8 
• Routine and research blood tests 
Day 15 
• Routine blood tests 
Day 22 
• Routine blood tests 
Subsequent Cycles 
Day 1 
• History and physical exam 
• Review of current medications and treatments 
• Routine and research blood tests 
• Durvalumab infusion 
• CT scan or MRI (every 8 weeks from third cycle) 
* Rectal swabs will be used to study microbes living in your gut, including sequence of 
microbial genes.  
Birth Control 
If you are a woman who is breast feeding or pregnant, you may not take part 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 at least two effective forms of birth control before starting study treatment, 
during study treatment, and for 6 months after you finish study treatment. If you are a man, you 
should not donate sperm before, during and for 6 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.   
Effective forms of birth control include:  
• abstinence  
• intrauterine device (IUD) 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:  16-C-0135 
CONTINUATION: page 6 of 15 pages 
 
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 
 
• hormonal [birth control pills, injections, or implants] 
• tubal ligation 
• vasectomy 
Risks or Discomforts of Participation 
What side effects or risks can I expect from being in this study? 
Tremelimumab: 
The following are side effects that have been associated with Tremelimumab: 
• Diarrhea 
• Rash 
• Pruritus (itching) 
• Fatigue 
• Nausea 
• Vomiting 
• Anorexia (loss of appetite) 
• Headache 
• Abdominal Pain 
• Auto-immune changes to the pituitary gland leading to hormonal changes. 
• 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.  
• Inflammation of the liver which is also known as hepatitis. In extreme cases this may 
result in liver failure and death.   
• Occasionally you can also get a skin rash related to the treatment and this can also result 
in severe and life threatening symptoms.  
• Problems related to Tremelimumab infusion 
• 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 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:  16-C-0135 
CONTINUATION: page 7 of 15 pages 
 
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 
 
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.  
Durvalumab 
Likely 
• Diarrhea 
• Rash/dry itchy skin 
• Liver problems: Increases in the blood level of substances called enzymes found within 
your liver cells may occur. The enzyme changes are unlikely to make you feel unwell. 
However, if these blood enzyme levels become very high, your study doctor may need to 
stop the study medication. A patient may develop inflammation of the liver called 
hepatitis, however this is uncommon. Signs and symptoms of this include yellowing of 
the skin or whites of the eyes, dark urine, severe nausea and vomiting, pain in the upper 
right side of your abdomen, skin itchiness, not feeling hungry and bleeding or bruising 
more easily than normal. 
• Fatigue 
• Difficulty breathing 
• Nausea 
• Constipation 
• Decreased appetite 
• Vomiting 
• Fever 
• Pain in muscles and joints 
Less Likely 
• Inflammation in the lungs (pneumonitis): Symptoms may include but are not limited to a 
new or worsening cough, shortness of breath possibly with fever. Preliminary data 
suggested that there may be the tendency of higher frequency and severity in Japanese 
patients compared with non-Japanese patients: Tell your study doctor right away if you 
have any of these symptoms as it may need to be treated urgently. 
• Low thyroid (Hypothyroidism): This is when the thyroid gland produces less thyroid 
hormone than it should which causes the metabolism to run too slow. Symptoms may 
include but are not limited to fatigue, increased sensitivity to cold, constipation, dry skin, 
unexplained weight gain, puffy face, muscle weakness, slow heart rate, thinning hair, 
impaired memory. The condition can be treated with replacement thyroid hormone. 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:  16-C-0135 
CONTINUATION: page 8 of 15 pages 
 
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 
 
• High thyroid (Hyperthyroidism): This is when the thyroid gland produces too much 
thyroid hormone. Symptoms include anxiety or nervousness, weight loss, frequent and 
loose bowel movements, breathlessness, feeling hot and possibly having heart 
palpitations. Depending on the severity of the symptoms treatment may include just 
monitoring the symptoms, treating the symptoms themselves and/or giving medicine to 
block the thyroid hormone. 
• Kidney problems: You may have an increase of creatinine levels in a blood test 
(creatinine is a protein marker that measures kidney function) but not have any symptoms 
or feel unwell. Less commonly a patient may experience nephritis which is an 
inflammation of the kidneys that stops the kidneys from working properly.  
• Nervous system problems: Symptoms can include unusual weakness of legs, arms, or 
face, numbness or tingling in hands or feet. In rare situations, there is the potential for the 
inflammation of the nervous system to be severe: Tell your study doctor right away if you 
have problems swallowing, if you start to feel weak very quickly and you are having 
trouble breathing. 
• Infusion Related Reactions: Reactions may occur during or after the infusion of study 
medication.  The reaction may cause fever or chills and a change in blood pressure or 
difficulty in breathing which might be serious. Tell your study doctor right away if you 
experience any of these symptoms even if it has been several days after the infusion has 
been completed.   
• Inflammation of the intestine (colitis). It may cause abdominal pain and diarrhea with or 
without blood. Fever may be present. It may require you to receive additional fluids. If 
left untreated, this may lead to a tear in the wall of the intestine which can be serious and 
life threatening. Tell your study doctor right away if you have any of these symptoms.  
Rare 
• Problems with your adrenal glands (Adrenal Insufficiency): May cause stomach pains, 
vomiting, muscle weakness and fatigue, depression, low blood pressure, weight loss, 
kidney problems, and changes in mood and personality. This event can occur commonly 
in patients who receive a combination of durvalumab and tremelimumab but has been 
reported uncommonly in patients who received durvalumab on its own. These 
complications may be permanent and may require hormone replacement. 
• Inflammation of the pancreas (pancreatitis). Pancreatitis usually causes symptoms of 
persistent upper abdominal pain (sometimes made worse by eating and drinking), nausea, 
vomiting and general weakness. Pancreatitis usually settles with simple measures but it 
can be a serious condition and can be fatal. You should immediately tell your study 
doctor if you develop any unusual symptoms. You may get an increase of lipase and 
amylase levels in a blood test (related to the pancreas) but not have any symptoms or feel 
unwell. Lipase and amylase are enzymes or protein markers that measure the function of 
your pancreas. Uncommonly these increases may be associated with pancreatitis. 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:  16-C-0135 
CONTINUATION: page 9 of 15 pages 
 
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 
 
• Type 1 Diabetes mellitus which may cause increased blood glucose levels (called 
‘hyperglycaemia’):  Symptoms may include weight loss, increased urination, increased 
thirst, and increased hunger. Type 1 diabetes will require replacement of insulin through 
injection. Tell your study doctor right away if you have any of these symptoms.    
• Allergic reactions: These can cause swelling of the face, lips and throat, breathing 
difficulties along with hives or nettle like rash. You should immediately tell your study 
doctor if you develop any of these symptoms.  
• Problems with the pituitary gland (hypopituitarism): Hypopituitarism refers to decreased 
output of hormones from the pituitary gland in the brain and may be caused by 
inflammation of the pituitary gland (hypophysitis). Symptoms may include headaches, 
thirstiness, and trouble seeing or double vision, leakage of breast milk or irregular periods 
in women. These complications may be permanent and may require hormone 
replacement. 
• Inflammation of the heart muscle (myocarditis). Symptoms can include chest pain, rapid 
or abnormal heart beat, shortness of breath and swelling of your legs. Tell your study 
doctor right away if you experience any of these symptoms. 
A new drug may show an increase in side effects or unexpected effects as more studies are 
conducted. For your safety, you will be followed closely by your Study Doctor and the study 
staff for any undesirable or unexpected side effects during your participation in this study and 
each time you receive durvalumab. 
There may be other side effects of durvalumab that are unknown. Other immune-mediated side 
effects are possible that have not been observed, and can result in inflammatory side effects in 
any organ or tissue. You will be told about any new findings that develop during the course of 
this study that may affect your decision to stay in the study. 
There is a remote chance that you may develop new allergies to previously exposed substances, 
other than Durvalumab or Tremelimumab. For example, it is possible that you could develop an 
allergy to shellfish or IV contrast while taking Durvalumab or Tremelimumab. These allergies 
may be severe and life threatening. 
Blood Sampling  
Bruising or bleeding at the needle site; rarely infection. This is treated with bandages, pressure 
and, if infection, antibiotic medicines. For more information about risks and side effects, ask 
your study team. 
Tumor Biopsy 
If your doctor determines it is safe we will obtain a piece of your tumor (biopsy) before you 
begin any study therapy, and on day 36 and day 85 using a needle with minimal risk to you.  You 
will be given local anesthesia (numbing medicine) and a sedative prior to the biopsy.  The biopsy 
will be taken through a needle put through the skin into your tumor.  After the procedure, the 
nurses will watch your blood pressure and other vital signs.  The baseline biopsy is mandatory 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:  16-C-0135 
CONTINUATION: page 10 of 15 pages 
 
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 
 
and you cannot participate in this study if you do not agree to this biopsy. The day 36 and day 85 
biopsies are optional. If the first biopsy is too difficult or if you experience too much discomfort 
as a result of it, you will be able to continue on the protocol without undergoing the second 
biopsy. However, an attempt at the first biopsy is needed to enter this study. There are other 
studies at NIH which may also be options for you and which do not involve biopsies.  
Radiation 
The tumor biopsy will be done by a specialist using an ultrasound or CT scanner to guide the 
biopsy needle into the tumor to ensure accuracy. To collect the research biopsies, you might be 
exposed to three 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 these procedures is 2.4 
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. 
Potential Benefits of Participation 
Are there benefits to taking part in this study? 
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.   
Alternative Approaches or Treatments 
Instead of being in this study, you have these options: 
• Getting treatment or care for your cancer without being in a study 
• Taking part in another study 
• 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. 
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: 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:  16-C-0135 
CONTINUATION: page 11 of 15 pages 
 
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 
 
• 
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.  
• 
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. 
• 
Medicines that are not part of the study treatment will not be provided or 
paid for by the Clinical Center, NIH. 
• 
Once you have completed taking part in the study, medical care will no 
longer be provided by the Clinical Center, NIH. 
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: 
• 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. 
• National Cancer Institute Institutional Review Board 
• Qualified representatives from MedImmune, Inc, the pharmaceutical company who 
produces tremelimumab and durvalumab. 
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.  
Genomic data of your microbes and your 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 
microbial 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. 
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 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:  16-C-0135 
CONTINUATION: page 12 of 15 pages 
 
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 
 
• if your disease comes back 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 
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. 
Conflict of Interest  
The National Institutes of Health (NIH) reviews NIH staff researchers at least yearly for conflicts 
of interest.  This process is detailed in a Protocol Review Guide.  You may ask your research 
team for a copy of the Protocol Review Guide or for more information.  Members of the research 
team who do not work for NIH are expected to follow these guidelines but they do not need to 
report their personal finances to the NIH. 
Members of the research team working on this study may have up to $15,000 of stock in the 
companies that make products used in this study.  This is allowed under federal rules and is not a 
conflict of interest.  
The National Institutes of Health and the research team for this study are using tremelimumab 
and durvalumab developed by MedImmune, Inc. through a joint study with your researchers and 
the company.   The company also provides financial support for this study.  
Use of Specimens and Data for Future Research 
To advance science, it is helpful for researchers to share information they get from studying 
human samples.  They do this by putting it into one or more scientific databases, where it is 
stored along with information from other studies. A researcher who wants to study the 
information must apply to the database and be approved.  Researchers use specimens and data 
stored in scientific databases to advance science and learn about health and disease.   
We plan to keep some of your specimens and data that we collect and use them for future 
research and share them with other researchers. We will not contact you to ask about each of 
these future uses.  These specimens and data will be stripped of identifiers such as name, address 
or account number, so that they may be used for future research on any topic and shared broadly 
for research purposes. Your specimens and data will be used for research purposes only and will 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:  16-C-0135 
CONTINUATION: page 13 of 15 pages 
 
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 
 
not benefit you.  It is also possible that the stored specimens and data may never be used.  
Results of research done on your specimens and data will not be available to you or your doctor.  
It might help people who have cancer and other diseases in the future.   
If you do not want your stored specimens and data used for future research, please contact us in 
writing and let us know that you do not want us to use your specimens and/or data.  Then any 
specimens that have not already been used or shared will be destroyed and your data will not be 
used for future research. However, it may not be possible to withdraw or delete materials or data 
once they have been shared with other researchers. 
 


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
STUDY NUMBER:  16-C-0135 
CONTINUATION: page 14 of 15 pages 
 
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 
 
 
 
OTHER PERTINENT INFORMATION 
1. 
Confidentiality.  When results of an NIH research study are reported in medical journals 
or at scientific meetings, the people who take part are not named and identified.  In most cases, 
the NIH will not release any information about your research involvement without your written 
permission.  However, if you sign a release of information form, for example, for an insurance 
company, the NIH will give the insurance company information from your medical record.  This 
information might affect (either favorably or unfavorably) the willingness of the insurance 
company to sell you insurance. 
The Federal Privacy Act protects the confidentiality of your NIH medical records.  However, you 
should know that the Act allows release of some information from your medical record without 
your permission, for example, if it is required by the Food and Drug Administration (FDA), 
members of Congress, law enforcement officials, or authorized hospital accreditation 
organizations. 
2. 
Policy Regarding Research-Related Injuries.  The Clinical Center will provide short-
term medical care for any injury resulting from your participation in research here.  In general, 
no long-term medical care or financial compensation for research-related injuries will be 
provided by the National Institutes of Health, the Clinical Center, or the Federal Government.  
However, you have the right to pursue legal remedy if you believe that your injury justifies such 
action. 
3. 
Payments.  The amount of payment to research volunteers is guided by the National 
Institutes of Health policies.  In general, patients are not paid for taking part in research studies at 
the National Institutes of Health.  Reimbursement of travel and subsistence will be offered 
consistent with NIH guidelines. 
4. 
Problems or Questions.  If you have any problems or questions about this study, or 
about your rights as a research participant, or about any research-related injury, contact the 
Principal Investigator, Tim Greten, M.D., Building 10, Room 12N226, Telephone:  240-760-
6114. You may also call the Clinical Center Patient Representative at 301-496-2626. If you have 
any questions about the use of your specimens or data for future research studies, you may also 
contact the Office of the Clinical Director, Telephone:  240-760-6070.  
5. 
Consent Document.  Please keep a copy of this document in case you want to read it 
again. 


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
STUDY NUMBER:  16-C-0135 
CONTINUATION: page 15 of 15 pages 
 
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 
 
 
 
 
COMPLETE APPROPRIATE ITEM(S) BELOW: 
A. Adult Patient’s Consent 
B. Parent’s Permission for Minor Patient. 
I have read the explanation about this study 
and have been given the opportunity to discuss 
it and to ask questions.  I hereby consent to 
take part in this study. 
I have read the explanation about this study 
and have been given the opportunity to discuss 
it and to ask questions.  I hereby give 
permission for my child to take part in this 
study.   
(Attach NIH 2514-2, Minor’s Assent, if 
applicable.) 
 
  
  
 
 
 
Signature of Adult Patient/ 
Legal Representative 
Date 
Signature of Parent(s)/ Guardian Date 
 
 
Print Name 
 
 
Print Name 
C. Child’s Verbal Assent (If Applicable) 
The information in the above consent was described to my child and my child agrees to 
participate in the study. 
 
  
  
 
Signature of Parent(s)/Guardian 
Date 
Print Name 
THIS CONSENT DOCUMENT HAS BEEN APPROVED FOR USE  
FROM MAY 8, 2017 THROUGH MAY 7, 2018.  
 
 
 
 
 
 
 
 
Signature of Investigator 
Date 
Signature of Witness 
Date 
 
 
Print Name 
 
 
Print Name 
 

Prot_SAP_000.pdf: 
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ICF_003.pdf: 
MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
INSTITUTE: 
National Cancer Institute 
STUDY NUMBER: 
16-C-0135 
PRINCIPAL INVESTIGATOR: 
Tim Greten, M.D. 
STUDY TITLE:  
A Pilot Study of Combined Immune Checkpoint Inhibition in Combination with 
Ablative Therapies in Subjects with Hepatocellular Carcinoma (HCC) or Biliary Tract 
Carcinomas (BTC) 
 
Continuing Review Approved by the IRB on 05/08/17 
Amendment Approved by the IRB on 06/26/17 (C) 
 
Date posted to web:  07/18/17 
Drug and Ablative Therapy 
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 (2) 
 
 
INTRODUCTION 
We invite you to take part in a research study at the National Institutes of Health (NIH). 
First, we want you to know that: 
Taking part in NIH research is entirely voluntary.  
You may choose not to take part, or you may withdraw from the study at any time.  In 
either case, you will not lose any benefits to which you are otherwise entitled.  However, 
to receive care at the NIH, you must be taking part in a study or be under evaluation for 
study participation. 
You may receive no benefit from taking part.  The research may give us knowledge that 
may help people in the future. 
Second, some people have personal, religious or ethical beliefs that may limit the kinds of 
medical or research treatments they would want to receive (such as blood transfusions).  If you 
have such beliefs, please discuss them with your NIH doctors or research team before you agree 
to the study. 
Now we will describe this research study.  Before you decide to take part, please take as much 
time as you need to ask any questions and discuss this study with anyone at NIH, or with family, 
friends or your personal physician or other health professional.   
Why is this study being done?  
This research is being done to study the safety and effectiveness of the combination of 
durvalumab (formerly known as MEDI4736) and tremelimumab with and without trans-arterial 
catheter chemoembolization (TACE), radiofrequency ablation (RFA), or cryoablation. 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 16-C-0135 
CONTINUATION: page 2 of 16 pages 
 
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 
 
As you are among the second group of ~ 50 subjects enrolling on the study, you will be assigned 
to take durvalumab and tremelimumab with TACE, RFA or cryoablation. The first group of 20 
subjects will be will be assigned to take durvalumab and tremelimumab without TACE, RFA or 
cryoablation. 
Tremelimumab is an experimental drug that has not been approved by the U.S. Food and Drug 
Administration (FDA). 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.  
Durvalumab is an investigational drug designed to boost the body’s immune system by targeting 
a protein on tumor cells called PDL-1. PDL-1 normally maintains the balance of the immune 
system. In cancer, PDL-1 helps tumors evade detection and elimination by the immune system. 
Durvalumab may increase the immune system’s ability to identify and destroy cancer cells. 
“Investigational” means that durvalumab has not been approved by the Food and Drug 
Administration (FDA) as either a prescription or over-the-counter drug.  
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). TACE, RFA, and cryoablation are standard procedures 
that are used to treat tumors. However, in this study RFA and cryoablation will be used in order 
to stimulate an immune response, rather than complete eradication of the lesion as per standard 
of care indication. Once it is determined which procedure you will receive your doctor will 
explain the procedure in full detail. 
This is the first study in which both drugs taken together will be tested in combination with 
TACE, RFA, or cryoablation, which is the main goal of this study. 
Why are you being asked to take part in 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. 
How many people will take part in this study?  
About 90 people will take part in this study. 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 16-C-0135 
CONTINUATION: page 3 of 16 pages 
 
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 
 
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: 
• Confirmation of diagnosis (You must provide a sample tumor tissue for an NCI lab to 
evaluate.  The tissue may be from a previous surgery or biopsy.  If none is available, we 
will ask you to undergo a biopsy to provide a fresh sample). 
• History and physical exam 
• Review of current medications and past treatments 
• Blood work 
• Urine laboratory tests 
• 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 
• A heart test called an electrocardiogram or ECG to check your heart 
• Urine or blood pregnancy test 
During the study 
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.  
Before you begin treatment, you will have a biopsy of your tumor using a needle. 
In this study, study therapy will be divided into cycles, each lasting 28 days. Treatment involves 
receiving tremelimumab and durvalumab through an IV on day 1 of each cycle. On day 36 you 
will receive the TACE, RFA or cryoablation procedure. You will have two additional biopsies of 
your tumor; one during TACE, RFA or cryoablation procedure and an optional one after you 
have completed the third cycle (day 85). Once you have complete 4 cycles of study therapy you 
will continue to receive durvalumab only, until your disease worsens, you experience intolerable 
side effects or you have completed 12 months of study therapy, whichever comes first.  
 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 16-C-0135 
CONTINUATION: page 4 of 16 pages 
 
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 
 
When you are finished taking the drugs (treatment) 
You will be seen within 60 days after completion of the study treatment to assess for possible 
delayed or ongoing side effects and overall clinical status. At this visit, you will have basic blood 
tests as well as blood collected for research purposes. 
Study Calendar 
Cycle 1 
Day 1 
• History and physical exam 
• Review of current medications and treatments 
• Routine and research blood tests 
• Research rectal swab*  
• Tumor biopsy 
• Tremelimumab infusion 
• Durvalumab infusion 
Day 8 
• Routine and research blood tests 
Day 15 
• Routine and research blood tests 
Day 22 
• Routine blood tests 
Cycle 2 
Day 1 
• History and physical exam 
• Review of current medications and treatments 
• Routine and research blood tests 
• Research rectal swab*  
• Tremelimumab infusion 
• Durvalumab infusion 
Day 8  
(Day 36) 
• Routine and research blood tests 
• RFA/TACE/Cryoablation (will be determined by 
your study doctor) and tumor biopsy during this 
procedure 
Day 15 
• Routine blood tests 
Day 22 
• Routine blood tests 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 16-C-0135 
CONTINUATION: page 5 of 16 pages 
 
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 
 
Cycle 3 
Day 1 
• History and physical exam 
• Review of current medications and treatments 
• Routine and research blood tests 
• Tremelimumab infusion 
• Durvalumab infusion  
• CT Scan or MRI 
Day 8 
• Routine and research blood tests 
Day 15 
• Routine blood tests 
Day 22 
• Routine blood tests 
Cycle 4 
Day 1 
(Day 85) 
• History and physical exam 
• Review of current medications and treatments 
• Routine and research blood tests 
• Research rectal swab*  
• Tumor biopsy (optional) 
• Tremelimumab infusion 
• Durvalumab infusion  
Day 8 
• Routine and research blood tests 
Day 15 
• Routine blood tests 
Day 22 
• Routine blood tests 
Subsequent Cycles 
Day 1 
• History and physical exam 
• Review of current medications and treatments 
• Routine and research blood tests 
• Durvalumab infusion 
• CT scan or MRI (every 8 weeks from third cycle) 
* Rectal swabs will be used to study microbes living in your gut, including sequence of 
microbial genes.  
Birth Control 
If you are a woman who is breast feeding or pregnant, you may not take part in the study because 
we don’t know how this medicine would affect your baby or your unborn child. If you are a 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 16-C-0135 
CONTINUATION: page 6 of 16 pages 
 
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 
 
woman who can become pregnant, or are the partner of a woman who can become pregnant, you 
will need to practice at least two effective forms of birth control before starting study treatment, 
during study treatment, and for 6 months after you finish study treatment.  If you are a man, you 
should not donate sperm before, during and for 6 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.   
Effective forms of birth control include:  
• abstinence  
• intrauterine device (IUD) 
• hormonal [birth control pills, injections, or implants] 
• tubal ligation 
• vasectomy 
Risks or Discomforts of Participation 
What side effects or risks can I expect from being in this study? 
Tremelimumab 
The following are side effects that have been associated with Tremelimumab: 
• Diarrhea 
• Rash 
• Pruritus (itching) 
• Fatigue 
• Nausea 
• Vomiting 
• Anorexia (loss of appetite) 
• Headache 
• Abdominal Pain 
• Auto-immune changes to the pituitary gland leading to hormonal changes. 
• 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.  


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 16-C-0135 
CONTINUATION: page 7 of 16 pages 
 
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 
 
• Inflammation of the liver which is also known as hepatitis. In extreme cases this may 
result in liver failure and death.   
• Occasionally you can also get a skin rash related to the treatment and this can also result 
in severe and life threatening symptoms.  
• Problems related to Tremelimumab infusion 
• 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 
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.  
Durvalumab 
Likely 
• Diarrhea 
• Rash/dry itchy skin 
• Liver problems: Increases in the blood level of substances called enzymes found within 
your liver cells may occur. The enzyme changes are unlikely to make you feel unwell. 
However, if these blood enzyme levels become very high, your study doctor may need to 
stop the study medication. A patient may develop inflammation of the liver called 
hepatitis, however this is uncommon. Signs and symptoms of this include yellowing of 
the skin or whites of the eyes, dark urine, severe nausea and vomiting, pain in the upper 
right side of your abdomen, skin itchiness, not feeling hungry and bleeding or bruising 
more easily than normal. 
• Fatigue 
• Difficulty breathing 
• Nausea 
• Constipation 
• Decreased appetite 
• Vomiting 
• Fever 
• Pain in muscles and joints 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 16-C-0135 
CONTINUATION: page 8 of 16 pages 
 
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 
 
Less Likely 
• Inflammation in the lungs (pneumonitis): Symptoms may include but are not limited to a 
new or worsening cough, shortness of breath possibly with fever. Preliminary data 
suggested that there may be the tendency of higher frequency and severity in Japanese 
patients compared with non-Japanese patients: Tell your study doctor right away if you 
have any of these symptoms as it may need to be treated urgently. 
• Low thyroid (Hypothyroidism): This is when the thyroid gland produces less thyroid 
hormone than it should which causes the metabolism to run too slow. Symptoms may 
include but are not limited to fatigue, increased sensitivity to cold, constipation, dry skin, 
unexplained weight gain, puffy face, muscle weakness, slow heart rate, thinning hair, 
impaired memory. The condition can be treated with replacement thyroid hormone. 
• High thyroid (Hyperthyroidism): This is when the thyroid gland produces too much 
thyroid hormone. Symptoms include anxiety or nervousness, weight loss, frequent and 
loose bowel movements, breathlessness, feeling hot and possibly having heart 
palpitations. Depending on the severity of the symptoms treatment may include just 
monitoring the symptoms, treating the symptoms themselves and/or giving medicine to 
block the thyroid hormone. 
• Kidney problems: You may have an increase of creatinine levels in a blood test 
(creatinine is a protein marker that measures kidney function) but not have any symptoms 
or feel unwell. Less commonly a patient may experience nephritis which is an 
inflammation of the kidneys that stops the kidneys from working properly.  
• Nervous system problems: Symptoms can include unusual weakness of legs, arms, or 
face, numbness or tingling in hands or feet. In rare situations, there is the potential for the 
inflammation of the nervous system to be severe: Tell your study doctor right away if you 
have problems swallowing, if you start to feel weak very quickly and you are having 
trouble breathing. 
• Infusion Related Reactions: Reactions may occur during or after the infusion of study 
medication.  The reaction may cause fever or chills and a change in blood pressure or 
difficulty in breathing which might be serious. Tell your study doctor right away if you 
experience any of these symptoms even if it has been several days after the infusion has 
been completed.   
• Inflammation of the intestine (colitis). It may cause abdominal pain and diarrhea with or 
without blood. Fever may be present. It may require you to receive additional fluids. If 
left untreated, this may lead to a tear in the wall of the intestine which can be serious and 
life threatening. Tell your study doctor right away if you have any of these symptoms. 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 16-C-0135 
CONTINUATION: page 9 of 16 pages 
 
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 
 
Rare 
• Problems with your adrenal glands (Adrenal Insufficiency): May cause stomach pains, 
vomiting, muscle weakness and fatigue, depression, low blood pressure, weight loss, 
kidney problems, and changes in mood and personality. This event can occur commonly 
in patients who receive a combination of durvalumab and tremelimumab but has been 
reported uncommonly in patients who received durvalumab on its own. These 
complications may be permanent and may require hormone replacement. 
• Inflammation of the pancreas (pancreatitis). Pancreatitis usually causes symptoms of 
persistent upper abdominal pain (sometimes made worse by eating and drinking), nausea, 
vomiting and general weakness. Pancreatitis usually settles with simple measures but it 
can be a serious condition and can be fatal. You should immediately tell your study 
doctor if you develop any unusual symptoms. You may get an increase of lipase and 
amylase levels in a blood test (related to the pancreas) but not have any symptoms or feel 
unwell. Lipase and amylase are enzymes or protein markers that measure the function of 
your pancreas. Uncommonly these increases may be associated with pancreatitis. 
• Type 1 Diabetes mellitus which may cause increased blood glucose levels (called 
‘hyperglycaemia’):  Symptoms may include weight loss, increased urination, increased 
thirst, and increased hunger. Type 1 diabetes will require replacement of insulin through 
injection. Tell your study doctor right away if you have any of these symptoms.    
• Allergic reactions: These can cause swelling of the face, lips and throat, breathing 
difficulties along with hives or nettle like rash. You should immediately tell your study 
doctor if you develop any of these symptoms.  
• Problems with the pituitary gland (hypopituitarism): Hypopituitarism refers to decreased 
output of hormones from the pituitary gland in the brain and may be caused by 
inflammation of the pituitary gland (hypophysitis). Symptoms may include headaches, 
thirstiness, and trouble seeing or double vision, leakage of breast milk or irregular periods 
in women. These complications may be permanent and may require hormone 
replacement. 
• Inflammation of the heart muscle (myocarditis). Symptoms can include chest pain, rapid 
or abnormal heart beat, shortness of breath and swelling of your legs. Tell your study 
doctor right away if you experience any of these symptoms. 
A new drug may show an increase in side effects or unexpected effects as more studies are 
conducted. For your safety, you will be followed closely by your Study Doctor and the study 
staff for any undesirable or unexpected side effects during your participation in this study and 
each time you receive durvalumab. 
There may be other side effects of durvalumab that are unknown. Other immune-mediated side 
effects are possible that have not been observed, and can result in inflammatory side effects in 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 16-C-0135 
CONTINUATION: page 10 of 16 pages 
 
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 
 
any organ or tissue. You will be told about any new findings that develop during the course of 
this study that may affect your decision to stay in the study. 
There is a remote chance that you may develop new allergies to previously exposed substances, 
other than Durvalumab or Tremelimumab. For example, it is possible that you could develop an 
allergy to shellfish or IV contrast while taking Durvalumab or Tremelimumab. These allergies 
may be severe and life threatening. 
 
TACE Procedure 
Likely 
Less Likely 
Rare but Serious 
• Abdominal pain 
• Fever 
• Nausea and/or vomiting 
• Abdominal fluid buildup 
(Ascites) 
• Bleeding 
(at 
catheter 
insertion site) 
• Allergy to iodine contrast 
agent  
• Liver failure 
• Kidney failure 
• Liver abscess formation  
• Stomach or duodenal ulcer 
• Pancreatitis 
• Cholecystitis (irritation of 
the gall bladder) 
• Arterial injury at catheter 
insertion site 
 
RFA Procedure 
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. It is the intent of this trial 
to use RFA to stimulate the immune system. RFA will intentionally treat only part of the 
tumor(s), even if that particular tumor can technically be eradicated. 
Cryoablation 
The risks from cryoablation procedure itself include a small chance of bleeding, injury to the 
normal liver tissue, and re-growth of the tumor.  Nerve damage may result. Completely frozen 
nerves can cause motor weakness or numbness in the area supplied by the nerves.  There should 
be minimal discomfort from the cryoablation procedure itself during the procedure, because you 
will be “asleep” under general anesthesia.  Following percutaneous cryotherapy, you should be 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 16-C-0135 
CONTINUATION: page 11 of 16 pages 
 
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 
 
able to resume your usual activities within one to three days. If you have had open cryoablation, 
you should be able to resume your usual activities within seven to 10 days. You should avoid 
lifting heavy objects for at least 72 hours. This will be discussed with you in greater detail prior 
to the procedure. It is the intent of this trial to use Cryoablation to stimulate the immune system. 
Cryoablation will intentionally treat only part of the tumor(s), even if that particular tumor can 
technically be eradicated. 
Blood Sampling  
Bruising or bleeding at the needle site; rarely infection. This is treated with bandages, pressure 
and, if infection, antibiotic medicines. For more information about risks and side effects, ask 
your study team. 
Tumor Biopsy 
If your doctor determines it is safe we will obtain a piece of your tumor (biopsy) before you 
begin any study therapy, on day 36 and day 85 using a needle with minimal risk to you.  You 
will be given local anesthesia (numbing medicine) and a sedative prior to the biopsy.  The biopsy 
will be taken through a needle put through the skin into your tumor.  After the procedure, the 
nurses will watch your blood pressure and other vital signs.  The baseline biopsy is mandatory 
and you cannot participate in this study if you do not agree to this biopsy. The day 36 biopsy will 
be performed during TACE/RFA/Cryoablation procedure. The day 85 biopsy is optional. If the 
first biopsy is too difficult or if you experience too much discomfort as a result of it, you will be 
able to continue on the protocol without undergoing the additional biopsy. However, an attempt 
at the first biopsy is needed to enter this study. There are other studies at NIH which may also be 
options for you and which do not involve biopsies. 
Radiation  
TACE/RFA/Cryoablation and Tumor biopsies will be done by a specialist using the CT scanner 
or ultrasound machine to guide any of these procedures to ensure accuracy. Thus, you might be 
exposed to three 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 these procedures is 3.0 
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.  
Potential Benefits of Participation 
Are there benefits to taking part in this study? 
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 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 16-C-0135 
CONTINUATION: page 12 of 16 pages 
 
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 
 
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.   
Alternative Approaches or Treatments 
Instead of being in this study, you have these options: 
• Getting treatment or care for your cancer without being in a study 
• Taking part in another study 
• 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. 
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: 
• 
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.  
• 
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. 
• 
Medicines that are not part of the study treatment will not be provided or 
paid for by the Clinical Center, NIH. 
• 
Once you have completed taking part in the study, medical care will no 
longer be provided by the Clinical Center, NIH. 
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: 
• 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. 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 16-C-0135 
CONTINUATION: page 13 of 16 pages 
 
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 
 
• National Cancer Institute Institutional Review Board 
• Qualified representatives from MedImmune, Inc, the pharmaceutical company who 
produces tremelimumab and durvalumab. 
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.  
Genomic data of your microbes and your 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 
microbial 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. 
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 comes back 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 
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. 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 16-C-0135 
CONTINUATION: page 14 of 16 pages 
 
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 
 
Conflict of Interest  
The National Institutes of Health (NIH) reviews NIH staff researchers at least yearly for conflicts 
of interest.  This process is detailed in a Protocol Review Guide.  You may ask your research 
team for a copy of the Protocol Review Guide or for more information.  Members of the research 
team who do not work for NIH are expected to follow these guidelines but they do not need to 
report their personal finances to the NIH. 
Members of the research team working on this study may have up to $15,000 of stock in the 
companies that make products used in this study.  This is allowed under federal rules and is not a 
conflict of interest.  
The National Institutes of Health and the research team for this study are using tremelimumab 
and durvalumab developed by MedImmune, Inc. through a joint study with your researchers and 
the company.   The company also provides financial support for this study.  
Use of Specimens and Data for Future Research 
To advance science, it is helpful for researchers to share information they get from studying 
human samples.  They do this by putting it into one or more scientific databases, where it is 
stored along with information from other studies. A researcher who wants to study the 
information must apply to the database and be approved.  Researchers use specimens and data 
stored in scientific databases to advance science and learn about health and disease.   
We plan to keep some of your specimens and data that we collect and use them for future 
research and share them with other researchers. We will not contact you to ask about each of 
these future uses.  These specimens and data will be stripped of identifiers such as name, address 
or account number, so that they may be used for future research on any topic and shared broadly 
for research purposes. Your specimens and data will be used for research purposes only and will 
not benefit you.  It is also possible that the stored specimens and data may never be used.  
Results of research done on your specimens and data will not be available to you or your doctor.  
It might help people who have cancer and other diseases in the future.   
If you do not want your stored specimens and data used for future research, please contact us in 
writing and let us know that you do not want us to use your specimens and/or data.  Then any 
specimens that have not already been used or shared will be destroyed and your data will not be 
used for future research. However, it may not be possible to withdraw or delete materials or data 
once they have been shared with other researchers. 
 


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
STUDY NUMBER:  16-C-0135 
CONTINUATION: page 15 of 16 pages 
 
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 
 
 
 
OTHER PERTINENT INFORMATION 
1. 
Confidentiality.  When results of an NIH research study are reported in medical journals 
or at scientific meetings, the people who take part are not named and identified.  In most cases, 
the NIH will not release any information about your research involvement without your written 
permission.  However, if you sign a release of information form, for example, for an insurance 
company, the NIH will give the insurance company information from your medical record.  This 
information might affect (either favorably or unfavorably) the willingness of the insurance 
company to sell you insurance. 
The Federal Privacy Act protects the confidentiality of your NIH medical records.  However, you 
should know that the Act allows release of some information from your medical record without 
your permission, for example, if it is required by the Food and Drug Administration (FDA), 
members of Congress, law enforcement officials, or authorized hospital accreditation 
organizations. 
2. 
Policy Regarding Research-Related Injuries.  The Clinical Center will provide short-
term medical care for any injury resulting from your participation in research here.  In general, 
no long-term medical care or financial compensation for research-related injuries will be 
provided by the National Institutes of Health, the Clinical Center, or the Federal Government.  
However, you have the right to pursue legal remedy if you believe that your injury justifies such 
action. 
3. 
Payments.  The amount of payment to research volunteers is guided by the National 
Institutes of Health policies.  In general, patients are not paid for taking part in research studies at 
the National Institutes of Health.  Reimbursement of travel and subsistence will be offered 
consistent with NIH guidelines. 
4. 
Problems or Questions.  If you have any problems or questions about this study, or 
about your rights as a research participant, or about any research-related injury, contact the 
Principal Investigator, Tim Greten, M.D., Building 10, Room 12N226, Telephone:  240-760-
6114. You may also call the Clinical Center Patient Representative at 301-496-2626. If you have 
any questions about the use of your specimens or data for future research studies, you may also 
contact the Office of the Clinical Director, Telephone:  240-760-6070.  
5. 
Consent Document.  Please keep a copy of this document in case you want to read it 
again. 


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
STUDY NUMBER:  16-C-0135 
CONTINUATION: page 16 of 16 pages 
 
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 
 
 
 
 
COMPLETE APPROPRIATE ITEM(S) BELOW: 
A. Adult Patient’s Consent 
B. Parent’s Permission for Minor Patient. 
I have read the explanation about this study 
and have been given the opportunity to discuss 
it and to ask questions.  I hereby consent to 
take part in this study. 
I have read the explanation about this study 
and have been given the opportunity to discuss 
it and to ask questions.  I hereby give 
permission for my child to take part in this 
study.   
(Attach NIH 2514-2, Minor’s Assent, if 
applicable.) 
 
  
  
 
 
 
Signature of Adult Patient/ 
Legal Representative 
Date 
Signature of Parent(s)/ Guardian Date 
 
 
Print Name 
 
 
Print Name 
C. Child’s Verbal Assent (If Applicable) 
The information in the above consent was described to my child and my child agrees to 
participate in the study. 
 
  
  
 
Signature of Parent(s)/Guardian 
Date 
Print Name 
THIS CONSENT DOCUMENT HAS BEEN APPROVED FOR USE  
FROM MAY 8, 2017 THROUGH MAY 7, 2018.  
 
 
 
 
 
 
 
 
Signature of Investigator 
Date 
Signature of Witness 
Date 
 
 
Print Name 
 
 
Print Name