Clinical trial: NCT02759835
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:
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.  
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: 16-C-0092 CONTINUATION: page 12 of 17 pages
Clinical trial: NCT02759835
Section: Confidentiality
Subsections: Will Your Medical Information Be Kept Private?|Certificate Of Confidentiality

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 Institutes of Health Intramural Institutional Review Board Qualified representatives from Astra Zeneca, the pharmaceutical company who produces osimertinib.
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. Your individual genomic data and health information will be put in a controlled-access database. This means that only researchers who apply for and get permission to use the information for a specific research project will be able to access the information. Your genomic data and health information will not be labeled with your name or other information that could be used to identify you. Researchers approved to access information in the database have agreed not to attempt to identify you.

To help us protect your privacy, we have obtained a Certificate of Confidentiality. The researchers can use this Certificate to legally refuse to disclose information that may identify you in any federal, state, or local civil, criminal, administrative, legislative, or other proceedings, for example, if there is a court subpoena. The researchers will use the Certificate to resist any demands for information that would identify you, except as explained below. You should also know that there are several circumstances in which the Certificate does not provide coverage. These include when information:
will be used for auditing or program evaluation internally by the NIH; or  
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: 16-C-0092 CONTINUATION: page 14 of 17 pages  
must be disclosed to meet the legal requirements of the federal Food and Drug  
  
Administration (FDA).  
is necessary for your medical treatment and you have consented to this disclosure; is for other research.
In addition, identifiable, sensitive information protected by this Certificate cannot be admissible as evidence or used for any purpose in any action, suit, or proceeding without your consent. You should understand that a Certificate of Confidentiality does not prevent you or a member of your family from voluntarily releasing information about yourself or your involvement in this research. If an insurer, employer, or other person obtains your written consent to receive research information, then the researchers will not use the Certificate to withhold that information.  
The Certificate of Confidentiality will not protect against the required reporting by hospital staff of information on suspected child abuse, reportable communicable diseases, and/or possible threat of harm to self or others.
Clinical trial: NCT02759835
Section: Duration of Study Involvement
Subsections: When You Are Finished Taking The Drugs (Treatment)

Approximately 30 days after you have finished taking the study drug, you will be asked to the return to the NIH for a medical history and physical exam, an ECG, routine blood tests for safety. After you are no longer coming to the Clinical Center for visits, we will contact you by phone every year to check on your health.
Clinical trial: NCT02759835
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:  
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.  
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: 16-C-0092 CONTINUATION: page 13 of 17 pages  
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.
Clinical trial: NCT02759835
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Risks Or Discomforts Of Participation What Side Effects Or Risks Can I Expect From Being In This Study?|The Risks You Might Experience Other Than The Drug Side Effects Are:|1. Psychological Or Social Risks Associated With Return Of Incidental Or Secondary Findings|2. Privacy Risks Associated With Return Of Incidental Or Secondary Findings|3. Protections Against Misuse Of Genetic Information|Potential Benefits Of Participation Are There Benefits To Taking Part In This Study?

Risks from osimertinib The medication used in this study may affect how different parts of your body work such as your liver, kidneys, heart, and blood. The study doctor will be testing your blood and will let you know if changes occur that may affect your health. There is also a risk that you could have side effects from the study drug.  
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: 16-C-0092 CONTINUATION: page 7 of 17 pages Here are important points about side effects:  
The study doctors do not know if you will or will not have side effects.  
Some side effects may go away soon, some may last a long time, or some may never go away.  
Some side effects may interfere with your ability to have children.  
Some side effects may be serious and may even result in death.
Here are important points about how you and the study doctor can make side effects less of a problem:  
Tell the study doctor if you notice or feel anything different so they can see if you are having a side effect.  
The study doctor may be able to treat some side effects. The study doctor may adjust the study drugs to try to reduce side effects.  
| side effects are found, the study doctor will discuss these with you.  Likely Less Likely Rare but Serious   Nausea   Diarrhea   Rash, Acne   Dry Skin, Itching   Infection of the skin  around a fingernail or  toenail   Eye Discomfort: burning /  itching / irritation /  smarting/ redness with or  without discharge   Blurred vision   Light sensitivity   Pneumonia   Pneumonitis, an  inflammation of lung tissue   Pleural Effusion, a  condition of excess fluid in  the pleural cavity, the  fluid-filled space that  surrounds the lungs   Interstitial Lung Disease  (ILD), a variety of  conditions characterized by  the scarring of lung tissue   Heart function: changes in  how well your heart pumps  with each beat   Change in heart rhythm   Increased levels of calcium  in the blood   Vision Changes   Septic Shock, a severe  infection where toxins can  cause a full-body  inflammatory response   Death 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   |
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The table below shows the most common and the most serious side effects that researchers know about. There might be other side effects that researchers do not yet know about. If important new side effects are found, the study doctor will discuss these with you.  
STUDY NUMBER: 16-C-0092 CONTINUATION: page 8 of 17 pages

Biopsies Risks associated with the biopsies include pain and bleeding at the biopsy site. We may need to perform a CT scan to guide the collection of tissue which would involve risks from radiation as described below. Radiation risks: You will be asked to undergo CT-guided biopsy before initiating treatment even if you had undergone a biopsy before. In case a biopsy at this time is not clinically safe and you had a biopsy done before, tissue will be obtained from the previous biopsy for the mutation testing needed for your eligibility for this protocol. A 2nd biopsy is also required after your first progression on osimertinib to detect the T790M mutation in EGFR to guide your therapy and also for research purposes. Another optional CT-guided biopsy may be requested when you finally come off protocol because of disease progression. One or more of these CT-guided biopsies may be for research purposes only and may or may not affect your future treatment. Therefore, the study may involve exposure to radiation from up 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 study 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. While there is no direct evidence that the amount of radiation exposure received from participating in this study is harmful, there is indirect evidence it may not be completely safe. There may be a very slight increase in the risk of cancer. Please tell your doctor if you have had any radiation exposure in the past year, either from other research studies or from medical tests or care, so we can make sure that you will not receive too much radiation. Radiation exposure includes x-rays taken in radiology departments, cardiac catheterization, and fluoroscopy as well as nuclear medicine scans in which radioactive materials were injected into your body. If you are pregnant you will not be permitted to participate in this research study. It is best to avoid radiation exposure to unborn or nursing infants since they are more sensitive to radiation than adults. Blood draw Risks associated with blood draw, which include pain and bruising, lightheadedness, and rarely, fainting  
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: 16-C-0092 CONTINUATION: page 9 of 17 pages Privacy Psychological or Social Risks Associated with Loss of Privacy in Genetic Research

As part of the research study, it is possible that you could learn that you have genetic risks for another disease or disability. This may be upsetting and, depending on what you learn, might create a need to make challenging decisions about how to respond. Although your genomic information is unique to you, you share some genomic similarities with your children, parents, brothers, sisters, and other blood relatives. Therefore, learning your research results could mean something about your family members and might cause you or your family distress.

Your privacy is very important to us and we will use many safety measures to protect your privacy. However, in spite of all of the safety measures that we will use, we cannot guarantee that your identity will never become known. While neither the public nor the controlledaccess databases developed for this project will have information such as your name, address, telephone number, or social security number, it may be possible to identify you based on the information in these databases and other public information (including information you tell people or post about yourself). The risk of this happening is currently very low. Although your genetic information is unique to you, you do share some genetic information with your children, parents, brothers, sisters, and other blood relatives. Consequently, it may be possible that genetic information from them could be used to help identify you. Similarly, it may be possible that genetic information from you could be used to help identify them. Patterns of genetic variation also can be used by law enforcement agencies to identify a person or his/her blood relatives. It is possible also that someone could get unauthorized access or break into the system that stores information about you. Every precaution will be taken to minimize this risk. There also may be other privacy risks that we have not foreseen.

Since some genetic variations can help to predict future health problems for you and your relatives, this information might be of interest to health care providers, life insurance companies, and others. However, Federal and State laws provide some protections against discrimination based on genetic information. For example, the Genetic Information Nondiscrimination Act (GINA) makes it illegal for health insurance companies, group health plans, and most employers to discriminate against you based on your genetic information. However, GINA does not prevent companies that sell life insurance, disability insurance, or long-term care insurance from using genetic information as a reason to deny coverage or set premiums. GINA also does not apply to members of the United States military, individuals 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: 16-C-0092 CONTINUATION: page 10 of 17 pages covered by the Indian Health Service, or veterans obtaining health care through the Veteran's Administration. Lastly, GINA does not forbid insurance medical underwriting based on your current health status though the Affordable Care Act limits consideration of pre-existing conditions by insurers.  
Risks of local ablative therapy (LAT) You will be required to sign separate consent forms at the time of LAT. Surgery, radiation therapy, or radiofrequency ablation have their own risks and these will be explained to you if and when you are eligible for that. You have the option of declining the LAT part of the study at that time. Prior osimertinib treatment may have unknown risks associated with subsequent LAT procedure, including radiation.

The aim of this study is to see if LAT and re-initiation of treatment with osimertinib can increase the time before your disease gets worse. 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 this strategy of LAT and re-initiation of osimertinib, 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: NCT02759835
Section: Procedures
Subsections: Description Of Research Study What Will Happen If You Take Part In This Research Study?|Clinical Assessments|Research Assessments|Standard Of Care Treatment:|Biopsy Procedure

Before you begin the study All research studies have specific criteria for entry to allow for valid interpretation of the study results and safety of participants, known as eligibility criteria. Before you begin this study, you will need to have the following 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. You may have already had these tests done as part of a NCI protocol, including the screening protocol. If you have recently undergone some of these tests, they may not need to be repeated.  
History and physical examination, including obtaining information about how you function in your daily activities Standard blood tests to measure your liver and kidney function, white blood cells, red blood cells and platelets, blood electrolytes and how quickly you form blood clots. If you are a woman able to get pregnant, you will also have a pregnancy test done. You will not be able to participate in the study if you are pregnant.  
Scans of your tumor Eye exam Electrocardiogram (ECG) Echocardiogram Review of your tumor sample from previous surgery or biopsy to confirm diagnosis and for genetic testing. If sufficient material does not exist, you will be asked to undergo a biopsy.
If you meet the eligibility criteria for this study you will be offered the option of participating and you will be asked to sign this informed consent document before participating in the study. During the study

You will have a physical examination, an ECG, and routine blood tests on day -1 and day 7 of your first course, then on day -1 of all subsequent courses. Scans to assess the response of your disease to the study therapy will be performed every 8 weeks. An echocardiogram will be performed every four months.  
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: 16-C-0092 CONTINUATION: page 5 of 17 pages

The following samples will be collected at baseline (before you have had your first dose of study drug) and day 7 of course 1 and on day -1 of subsequent courses:  
**Blood sample:** We will ask you to provide up to 50mL (approximately 3.5 tablespoons)
of blood at the above time points. The maximum amount of blood taken from you is based on your age and will not be more than the blood volume limit set for research by the NIH.  
**Urine sample:** We will ask you to provide up to 45 mL of urine at each sampling time point, if feasible. We may also provide you with a container to collect urine for a 24hr period at home, or during your stay in the NIH Clinical Center.  
**Saliva sample:** We will ask you to provide a saliva sample, if possible, each time you provide us with your blood and urine samples. We will provide you with a container with specific instructions to get your saliva samples.  
The above samples will be analyzed for alterations in genes and proteins.
We will also collect tumor tissue at the beginning of the study before you have taken any study medication (if we have enough tissue left from your sample at screening, we will use that), and after your disease worsens for the first time. We may also collect a sample after your disease has worsened for the second time, but this is optional, and we will ask your permission to do so later on in the consent. If you undergo surgery as your form of LAT, the tumor sample will be obtained at that time. If you are not undergoing surgery at the time the sample is needed, you will have to undergo a biopsy, a description of which is provided later.

Treatments covered under this study may include a single medication or a combination of medications, surgery or radiation to treat your cancer. These treatments will not be experimental. Your doctors will describe your treatment plan to you in detail before asking you to sign this  
  
STUDY NUMBER: 16-C-0092 CONTINUATION: page 6 of 17 pages consent form. You may be asked to sign a separate consent form for any treatment procedures not outlined in this consent.

A mandatory tumor biopsy will be obtained before starting treatment and after first progression.  
You will be asked about another tumor biopsy at second progression. This biopsy will be optional. If your doctor determines it is safe we will obtain a piece of your tumor (biopsy) using a needle. This process will be guided by a CT scan or bronchoscopy and is minimally invasive. You will be given local anesthesia (numbing medicine). 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.
Clinical trial: NCT02759835
Section: Purpose of Research
Subsections: Why Is This Study Being Done?

This study is being done in order to test the effect of local ablative therapy (LAT) in the treatment of your cancer after progression of disease on the investigational drug, osimertinib (AZD9291, Tagrisso), provided there are no more than 5 sites of your disease suitable for treatment with LAT (surgery, radiation therapy, radiofrequency ablation, or cryoablation).  
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: 16-C-0092 CONTINUATION: page 2 of 17 pages Normally, cells in your body divide in an orderly way. However, in cancer, some cells start to behave abnormally resulting in faster growth and multiplication. Osimertinib is an experimental treatment for patients with non-small cell lung cancer (NSCLC) whose lung cancer is due to the development of specific changes in the gene that produces a protein on the surface of the cell called the epidermal growth factor receptor (EGFR). When the gene changes it is said to have developed a mutation. Patients who have NSCLC with a mutation in EGFR can be treated by specific drugs called EGFR tyrosine kinase inhibitors (EGFR TKIs). Unfortunately, after a period of therapy with EGFR TKIs, a significant number of tumours will develop resistance to this treatment due to a second EGFR mutation called T790M. Osimertinib has been approved by the Food and Drug Administration (FDA) for treatment of recurrent lung cancer with T790M mutation in EGFR after progression on drugs targeting other
"sensitizing" mutations in EGFR and has been shown to delay cancer progression. However, osimertinib is not approved for use as the initial treatment of lung cancer with EGFR mutations, treatment of patients without the T790M mutation, or re-initiation of treatment after LAT. Hence treatment with osimertinib is experimental in this study. There are only two FDA-approved treatments for patients whose disease has progressed on osimertinib (Nivolumab/Opdivo and Pembrolizumab/Keytruda). Thus, assessing the effectiveness of LAT as a strategy to extend the benefits of osimertinib merits further investigation.
Clinical trial: NCT02759835
Section: Voluntary Participation
Subsections: Why Are You Being Asked To Take Part In This Study?|C. Child'S Verbal Assent (If Applicable)

You have been asked to take part in this study because you have been diagnosed with non-small cell lung cancer that has an EGFR mutation, with any of the following characteristics:  
You have not been treated with any EGFR TKI. (cohort 1) Your lung cancer has progressed after treatment with other EGFR TKIs and now it has the EGFR T790M mutation. (cohort 2)
Your lung cancer has progressed while being treated with osimertinib and there are no more than 5 sites of your disease that have progressed and are suitable for treatment with LAT (surgery, radiation therapy or radiofrequency ablation). (cohort 3)

The information in the above consent was described to my child and my child agrees to participate in the study.  
| study.   |
|----------|  
Signature of Parent(s)/Guardian Date Print Name  
| THIS CONSENT DOCUMENT HAS BEEN APPROVED FOR USE  FROM JANUARY 28, 2019 THROUGH FEBRUARY 4, 2020.   |      |                      |      |
|----------------------------------------------------------------------------------------------------|------|----------------------|------|
| 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: NCT02759835
Section: Withdrawal from Study
Subsections: Stopping Therapy

Your doctor may decide to stop your therapy for the following reasons:  
if he/she believes that it is in your best interest if your disease comes back after LAT or if you are not eligible for LAT
if you have side effects from the treatment that your doctor thinks are too severe if new information shows that another treatment would be better for you if AstraZeneca is no longer able to supply osimertinib
In this case, you will be informed of the reason therapy is being stopped. If your doctor decides to stop your therapy because your disease has come back, and that disease is later found to be a non-cancerous diagnosis such as infection or inflammation, you may be able to restart treatment as long as you continue to meet the study's enrollment requirements and have not stopped taking the study drug for more than one month. You can stop taking part in the study at any time. However, if you decide to stop taking part in the study, we would like you to talk to the study doctor and your regular doctor first. If you decide at any time to withdraw your consent to participate in the trial, we will not collect any additional medical information about you. However, according to FDA guidelines, information collected on you up to that point may still be provided to the pharmaceutical company 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.