Clinical trial: NCT03394027
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, with standard**
chemotherapy or CDK4/6 inhibitors.  
- **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.
Clinical trial: NCT03394027
Section: Confidentiality
Subsections: Release Of Genetic Information|Who Else Besides The Investigators On This Study Will Know The Results Of My Sample Testing?|Will Your Medical Information Be Kept Private?|Certificate Of Confidentiality

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. 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. While the databases developed for this project are not open to everyone and also will not contain information that is traditionally used to identify you, such as your name, address, telephone number, or social security number, people may develop ways in the future that would allow someone to link your genetic or medical information in our databases back to you. For example, someone could compare information in our databases with information from you (or a blood relative) in another database and be able to identify you (or your blood relative). It also is possible that there could be violations to the security of the computer systems used to store the codes linking your genetic and medical information to you. Your individual genomic data and health information may 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. 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.  
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  
  
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. 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 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.

Once we obtain any of the samples listed above, the investigators take all your personal information off those samples and label them with a study code number. Only the investigators on this study know who the sample came from. The key linking your personal information with the code number is kept in a secure computer data base, with access only to the 2-3 research staff who will be discussing this study with you. Once the sample has been labeled with a code, it is sent to a variety of NIH laboratories for storage and testing. No one testing your samples will be able to link the results to you personally. Specimens obtained during your participation in this study may be sent for testing to investigators outside of NCI or the NIH. All samples will be coded to protect your privacy and no personal information will be included. Other investigators on this study will have access to limited clinical and biologic data such as age, gender and disease status.

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.  
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 Institutes of Health Intramural Institutional Review Board**  
- **Qualified representatives from Oncoceutics, Inc., the pharmaceutical company who**
produces ONC201.
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. We may put your research data in a large database for broad sharing with the research community. These databases are commonly called data repositories. These data repositories might or might not be located at the NIH. **The information in this database could include but is** not limited to genetic information, ethnicity and sex. **If your individual research data is placed** in one of these repositories**, it will not be labeled with your name or other information that** could be used to easily identify you, **and only qualified researchers will be able to look at your** data. These researchers must receive prior approval from individuals or committees to access the data. Your summary genomic data is being placed in an unrestricted database, so researchers will be able to access summary information about all the participants included in the study (including you), or summary information combined from multiple studies, without applying for permission. The risk of anyone identifying you with this information is very low.

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**
- **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.  
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  
  
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: NCT03394027
Section: Duration of Study Involvement
Subsections: During The Study|When You Are Finished Taking The Drugs (Treatment)|How Long Will Your Samples Be Stored?

During the study, the study doctor and staff will monitor you for any side effects and monitor your cancer. You may receive supportive care to manage side effects during this study. Ask the study doctor or staff if you have questions about supportive care. Each cycle is 28 days long. You will take ONC201 weekly for a total of 4 doses of ONC201 during 1 cycle. During Cycle 1, you will receive weekly phone calls to ask about whether there have been any changes to your health and about any other medications that you may be taking.  
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 be invited for a follow up safety visit approximately one month after the last day you take the study drug. At this visit, you will have the following tests:
- **Physical exam and vitals**
- Review of your symptoms and your ability to perform your normal activities.  
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  
  
- **Routine blood tests to find out if you are anemic, have low blood counts, your blood is**  
  
clotting normally and if your liver, kidneys, and other organs are working well.  
- **You will also be given the option for another biopsy of your tumor as well as for research**
labs. These tests may help researchers determine why your tumor didn't response or stopped responding to treatment.

The samples collected during this study will be stored for as long as the study is open. When this study is closed, we would like to keep the samples for future research. We will request your permission to do so, later in this consent.
Clinical trial: NCT03394027
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.  
- **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: NCT03394027
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Birth Control|Risks Or Discomforts Of Participation|What Side Effects Or Risks Can I Expect **From Being In This Study?** Potential Side Effects From Onc201|Risk Of Radiation|Potential Benefits Of Participation Are There Benefits To Taking Part In This Study?

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 two effective forms of birth control before starting study treatment, during study treatment, and for at least one month 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**

As with all treatments, there are several side effects or risks from the treatment provided in this study. However, doctors don't know all the side effects that may happen with this drug, so it is  
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**  
NIH-2514-1 (07-09)  
NIH-2514-2 (10-84)  
P.A.: 09-25-0099 File in Section 4: Protocol Consent  
for NIH 2514-2, Minor Patient's Assent to Participate In A Clinical Research Study STUDY NUMBER: 18-C-0034 CONTINUATION: page 8 of 16 pages important to report any changes that you notice, even if your study team does not ask specifically about them. Side effects may be mild or severe. Your study team will give you medicines to help lessen side effects. Many side effects go away with those medicines and others may go away soon after you stop treatment. In some cases, side effects can be serious, long-lasting, or may never go away. In very rare instances, they could cause death.

To date, over 70 patients have taken at least one dose of ONC201 and it has been generally well tolerated. Very few side effects have been attributed to ONC201.  
| Likely                 | Less Likely                                                                                                                                                                                                                                                                                                                                                                                                                             | Rare but Serious   |                               |    |                    |
|------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------|-------------------------------|----|--------------------|
| -                      | Fever                                                                                                                                                                                                                                                                                                                                                                                                                                   | -                  | Elevated Amylase              | -  | Twitching          |
| -                      | Fatigue (tiredness)                                                                                                                                                                                                                                                                                                                                                                                                                     | -                  | Nausea/Vomiting               | -  | Abnormal breathing |
| -                      | Rash                                                                                                                                                                                                                                                                                                                                                                                                                                    | -                  | Abnormal walking or  standing |    |                    |
| -                      | Stroke, also known as  cerebrovascular  accident (CVA). This  is the sudden death of  brain cells due to lack  of oxygen, caused by  blockage of blood  flow or rupture of an  artery to the brain.  Sudden loss of speech,  weakness, or paralysis  of one side of the body  can occur. It may  have a long-term  effect on brain  function, and it could  be fatal. At this time it  is unclear if it's linked  to the use of ONC201. |                    |                               |    |                    |
| -                      | Neutropenia                                                                                                                                                                                                                                                                                                                                                                                                                             |                    |                               |    |                    |
| 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                                                                                                                                                                                                                                                                                                           |                    |                               |    |                    |

This research study involves exposure to radiation from up to 3 CT scans that may be used during your tumor biopsies. 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 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 infants since they are more sensitive to radiation than adults.

The aim of this study is to see if treatment with ONC201 **will cause your tumors to shrink. We** do not know if you will receive personal, medical benefit from taking part in this study. These potential benefits could include shrinking of your tumor or lessening of your symptoms, such as pain, that are caused by the cancer. Because there is not much information about the drug's effect on your cancer, we do not know if you will benefit from taking part in this study, although the knowledge gained from this study may help others in the future who have cancer.
Clinical trial: NCT03394027
Section: Procedures
Subsections: Description Of Research Study What Will Happen If You Take Part In This Research Study? Before You Begin The Study|What Tests Will Be Done On My Samples?|Tumor Biopsy|Blood Sampling

Certain standards (criteria) have been established to ensure that you are a medically appropriate candidate for this trial. These criteria also make sure that the results of this study can be used to help make decisions about treating other patients. 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.  
- **A review of any past or current medical conditions, medicines you are taking and cancer**
history.  
- **Physical examination, including height, weight, vital signs**
- **Electrocardiogram (EKG - a record of your heartbeat)**
- Review of your symptoms and your ability to perform your normal activities.  
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  
- **Imaging Assessments - a computed tomographic scan (CT) that produces a picture of**
your body using a small amount of radiation and magnetic resonance imaging (MRI) that uses a magnetic field to produce an image of your body. These will be used to examine your chest, abdomen, pelvis, bones and brain.  
- **You will have blood drawn for:**
o **routine blood tests to find out if you are anemic, have low blood counts, and if your**
liver, kidneys, and other organs are working well.  
o **Tests for HIV, Hepatitis B and Hepatitis C.**
- **If you have not been tested for BRAC ½ mutations (for breast cancer) or for Lynch**
Syndrome (for endometrial cancer), a small amount of blood will be collected for genetic analysis. If you have been previously tested for these mutations, you will not need to have blood drawn for this as long as you can show the researchers the test results.  
- **Pregnancy serum or urine test if you are a woman who can have children.** - **You will be asked to provide a pathologist's report from an accredited laboratory or**
sample of your tumor from a previous surgery so that we may confirm your diagnosis.
If you are eligible to participate in this trial and wish to do so, an image-guided biopsy of your tumor will be required for research purposes before you start treatment. To help researchers determine the way ONC201 works on tumor cells, an additional image-guided biopsy will be required after you have had 5 weekly doses of ONC201. If/when your tumor no longer responds to the treatment and it starts to grow, you can decide if you would like to undergo an additional image-guided biopsy so that researchers can study what made the tumors stop responding to ONC201.

Your tissue (tumor and normal tissue) and blood that are collected will be used to look for specific changes in the cell signaling, DNA repair, mitochondrial, or other pathways in tumors.  
This analysis could be used to develop new ways of diagnosing and treating cancer. In order to examine the tumor and normal tissue, we may use several different techniques depending on the type of tissue we collect. Also, we will look for changes of DNA damage repair markers, circulating tumor cells, and immune cells in the blood. We will study whether these changes link to your health outcomes. When we are conducting these tests, it is possible that we could identify possible changes in other parts of your DNA that are not related to this research. These are known as "incidental medical findings." However, the analyses that we perform in our laboratory are for research purposes only; they are not nearly as sensitive as the tests that are performed in a laboratory that  
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  
is certified to perform genetic testing. Changes that we observe unrelated to our research may or may not be valid. Therefore, we do not plan to inform you of the results of testing on your tissue and blood that is performed in our research lab. However, in the unlikely event that we discover a finding that is believed to be clinically important based on medical standards at the time that we first analyze your results, we will contact you. This could be many years in the future. We will ask you to have an additional tube of blood drawn to verify the findings we have seen in our lab. If the results are verified, you will be re-contacted and offered a referral to a genetic healthcare provider to discuss the results

If your doctor determines it is safe we will obtain a piece of your tumor (biopsy) 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. Depending upon the location of your tumor, a CT scan or other imaging modality such as an ultrasound may be used to assist the biopsy. After the procedure, the nurses will watch your blood pressure and other vital signs. This biopsy is not optional and you cannot participate in this study if you do not agree to the biopsy. If the first biopsy is too difficult, you will be able to continue on the protocol without undergoing the second (required) and third (optional) biopsies. 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.

Risks of blood sampling include 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.  
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
Clinical trial: NCT03394027
Section: Purpose of Research
Subsections: Why Is This Study Being Done?

You are taking part in the Phase II study of an investigational drug called ONC201. The main purpose of this study is to see if ONC201 will help to shrink tumors in people with certain types of breast or endometrial cancers. This study also looks at how long the tumors respond to the  
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)  
  
treatment. ONC201 is manufactured by Oncoceutics, Inc and is not approved by the United States (U.S.) Food and Drug Administration (FDA) to treat any type of breast, or endometrial cancer, or any other type of disease. The exact mechanism of ONC201 is unknown at this time, but we suspect that it works through interrupting activity of the mitochondria (the "powerhouse" of the cell). Mitochondria are important for metabolism of all cells but cancer cells rely more heavily on mitochondria for their function than normal cells. The researchers in this study hope that by blocking the mitochondrial activity it will cause tumor cells to die, thereby shrinking tumors.
Clinical trial: NCT03394027
Section: Voluntary Participation
Subsections: Why Are You Being Asked To Take Part In This Study?

You are being asked to take part in this study because you have:  
- **Metastatic estrogen receptor positive breast cancer OR** - **Metastatic triple negative breast cancer OR** - **Advanced or metastatic endometrial cancer**
How many people will take part in this study? Up to 90 people will take part in this study.
Clinical trial: NCT03394027
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 during treatment** - **if you become pregnant**
- **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 the study is closed for any reason  
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  
  
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 Oncoceutics, Inc. or their 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.