Clinical trial: NCT03056001
Section: Alternatives
Subsections: What Other Choices Do I Have If I Do Not Take Part In This Study?

You do not need to take part in this research study. Your study doctor is willing to discuss the benefits and side effects of other forms of treatment other than this study that are available. These include:  
- Other usual chemotherapy for your type of cancer.  
- Other investigational research studies with chemotherapy, hormones, radiation therapy, or new anti-cancer agents that may be available for your disease.  
- Choosing no further treatment. If you decide that you don't want any more active treatment, one of your options is called "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, but instead tries to improve how you feel. Comfort care tries to keep you as active and comfortable as possible. If you think you might prefer comfort care, please discuss this with your family, friends and your doctor.
Clinical trial: NCT03056001
Section: Confidentiality
Subsections: Specimen Confidentiality|Will My Medical Information Be Kept Private?|Authorization To Disclose Health Information

There is a small risk that your protected health information may be released during the processing of your specimens for research. Everything possible will be done to ensure your privacy and confidentiality is maintained. Your specimens will be labeled with a code that does not identify you. Only your study doctor, clinic staff, and a small number of study staff will know your identity.

The records of this study will be kept private. In any sort of report we might publish, we will not include any information that will make it possible to identify a patient. Your record for this study may, however, be reviewed and/or photocopied by Atrium Health, Merck, Inc. (funding company),  
or by representatives of the Food and Drug Administration or other government agencies. To that extent, confidentiality is not absolute. To ensure that your information collected for this study will be kept private, your name will not be used whenever possible. A code will be used instead of your name. All of your study data will be kept in a secure location. Your de-identified specimens for research (with only your unique ID number) will be stored in a biospecimen repository (a "bank" of specimens) at Atrium Health. Your specimens may be used to determine the sequence of some or all of your genes (DNA - traits passed in families). However, this study is not intended to identify diseases causing mutations that can affect the health of close family members (such as your parents, siblings, or children). All specimens for research collected for the purposes of this study will be considered donated materials and will be stored indefinitely. 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.

If you wish to take part in this clinical study, you will be asked to sign this consent form. It allows the study Sponsor-Investigator (Dr. Livingston) to collect and process any relevant personal health information collected from you during the study. These are activities routinely carried out during all clinical studies. You have been told that personal information about you (including sensitive personal health information, such as your medical history and your racial/ethnic origin if relevant to the study) will be reviewed, collected on a computer database, stored in electronic or manual files, audited, and/or otherwise processed by:
- the clinical study sponsor-investigator, investigators and research staff,
- regulatory or other governmental authorities of the United States and other countries,
- other persons authorized by the study sponsor,
- Merck, Inc. employees,
- Atrium Health employees,
- other persons or agencies as required by law or allowed by federal regulations.  
You have been told that your personal data are being collected and processed to:
- check your suitability to take part in the study, - monitor your treatment with the study drug,
- compare and pool study treatment results with those of other subjects in clinical studies,  
- support the development of the study drug,
- support the licensing application for regulatory approval of the study drug in the world
- support the marketing, distribution, sale and use of the study drug anywhere in the world.  
You have been told that your personal information may be processed within the U.S. or elsewhere in the world or transferred to or from the U.S. for review, processing and/or storage by an associated company or a carefully selected third-party organization. By signing this document, you explicitly consent to the transfer of your personal information, including sensitive personal information, collected during this clinical study, for review, processing and/or storage. Your personal health information may be further shared by the groups above. If shared by them, the information will no longer be covered by the Privacy Rule. However, the groups are committed to keeping your personal health confidential. You may refuse this authorization to transfer your personal information. If you choose not to agree to this authorization, you might be ineligible to participate in the study. If you decide not to sign this authorization, that will not harm your relations with your doctors or with Atrium Health. You have the right to inspect your medical record at any time. Your research record may be unavailable until the conclusion of the study. At that point, it will be available. Please speak with the study doctor if you desire to access your record. You have been told whenever your personal information is processed, it will be kept confidential and secure, to the best of our ability. It will be used only for the purpose for which it was collected. This Authorization does not have an expiration date. You have been told that according to the guidelines for good clinical practice, the study investigator and sponsor will keep your personal information for at least 6 years. If you do not withdraw this Authorization in writing, it will remain in effect indefinitely. If you wish to revoke authorization to use your personal information, you will notify the study doctor in writing at the address and telephone number listed on the first page of this form. Some of the data obtained from your record prior to your revocation may still be used if considered necessary for the study.
Clinical trial: NCT03056001
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Risks|Less Common (4% To 20%)|Reproductive Risk:|Allergic Reaction|Ct Scan/Mri|Tumor Biopsy|What Happens If I Am Injured Because I Took Part In This Study?

You may have side effects while on the study. Everyone taking part in the study will be watched carefully for any side effects. However, doctors don't know all the side effects that may happen. Side effects may be mild or very serious. Your health care team may give you medicines to help lessen side effects. Many side effects go away soon after you stop taking the drugs. In some cases, side effects can be serious, long-lasting, or may never go away. A severe side effect rarely may be lifethreatening. You should tell your study doctor immediately if you experience any side effects.  
This study has several risks. First, it is possible that you will get the new study treatment but do less well than you have been doing. Second, because the study treatment is new, we may not yet know all the side effects and something unexpected could happen. The following known side effects of pembrolizumab and doxorubicin are listed below.

- Heart failure or heart attack which may cause shortness of breath, swelling of ankles, cough or tiredness which may occur years after the dose
- Swelling of the body which may cause shortness of breath
- Swelling and redness at the site of the study drug injection or area of previous radiation - Belly pain - Sores in the mouth, throat or stomach
- Nausea, diarrhea
- Hepatitis (liver infection) which may cause yellow eyes and skin
- Allergic reaction which may cause rash, low blood pressure, wheezing, shortness of breath, swelling of the face or throat
- Cancer of the bone marrow (leukemia) caused by chemotherapy
- Damage to organs which may cause infection, bleeding, may require transfusions (receiving blood from another person)
- Darkening of the nail beds or skin or hands and feet - Loss of nails

You should not become pregnant or father a baby while on this study and for 4 months after the last dose of pembrolizumab and 6 months after the last dose of doxorubicin because the drugs in this study can affect an unborn baby. Women should not breastfeed a baby while on this study and for 4 months after the last dose of pembrolizumab and 6 months after the last dose of doxorubicin. If you are of childbearing potential, you must agree to use an acceptable method of birth control during the study and for 4 months after the last dose of pembrolizumab and 6 months after the last dose of doxorubicin. Your study doctor will discuss with you which birth control methods are considered acceptable. Should you become pregnant or suspect you are pregnant while on this study, you should inform your study doctor immediately.  
If you become pregnant, you will be removed from the study and may also be asked questions about your pregnancy and the baby. Male subjects should also inform the study doctor immediately if their sexual partners become pregnant while the subject is receiving study treatment.

As with all medications, side effects may include allergic reaction. Allergic reactions may range from mild to severe reactions, such as itching or rash, to major life-threatening reactions which can result in death.

A CT scan exposes you to a small dose of radiation. Although all radiation you receive builds up over a lifetime, this amount of radiation should not create a significant risk to your health. Contrast dye is usually injected when you a get a CT scan. The contrast dye may cause pain or burning when it is injected and may worsen kidney function in people who already have kidney disease or who are dehydrated (have not had enough liquids for that day). The contrast dye may also cause an allergic reaction, which could be severe and life threatening. There are risks from an MRI if you are pregnant or have one of the following: an artificial heart valve, pacemaker, metal plate, pin, or other metallic objects in your body (including gun shot or shrapnel). You may also become anxious from lying in a tight space without moving. The MRI scan does not cause any pain and does not expose you to x-ray radiation.

The risks of a biopsy can include bleeding, pain, and infection. To reduce these risks, the site of the biopsy will be numbed, and sterile techniques will be used. You will sign a separate consent for this procedure.

If you become ill or are hurt while you are in the study, get the medical care that you need right away. In the event that you are harmed as a result of your participation in this study, inform your study doctor immediately so you can access medical treatment. You and/or your health plan will be charged for this treatment in the usual manner. The study will not pay for standard medical treatment.  
You still have the right to make a claim through the legal system even if you sign and date this form, accept medical care, or accept payment for medical expenses.
Clinical trial: NCT03056001
Section: Procedures
Subsections: How The Study Works Before You Begin The Study (Screening; One Visit):|During The Study (Intervention; Number Of Visits/Cycles):|After You Complete The Intervention (Post-Intervention; One Visit):|Additional Post-Study Treatment Follow-Up:

You will need to have the following tests and procedures done to determine if you can be in the study. These exams, tests, and procedures are part of regular cancer care and may be done even if you do not join the study. If you have had some of them recently, they may not need to be repeated. This will be up to your study doctor.  
- Medical history
- Physical examination including vital signs (heart rate, blood pressure, breathing rate, temperature) and height/weight measurements
- Documentation of any medicines you are taking
- You will be asked about the extent of your physical activity and how you are generally feeling
- CT (computed tomography - special x-ray using computers) scan with contrast dye or MRI
(magnetic resonance imaging - special x-ray using magnets and a computer) of the tumor site, chest, abdomen and pelvis
- Electrocardiogram (ECG), a paper tracing of the electrical activity of your heart and echocardiogram (ECHO), a test of the action of the heart using ultrasound waves
- Pregnancy test (urine or blood) if you are a female of childbearing potential - Blood work to check blood counts, blood chemistry (measure of chemicals in the blood),
and blood clotting
- Urine test
The following tests and procedures will be done specifically for this study and are not part of regular cancer care:
- Tumor biopsy - you will be asked to have a tissue sample taken from an area where your disease is located. You will sign a separate consent for this procedure. If you are unwilling to have this biopsy or if your study doctor determines that a biopsy would be unsafe, we may collect tissue from a recent biopsy within 12 months of beginning study treatment.  
- Blood work to test thyroid hormone levels
- Blood work for correlative (related) studies (looks at certain features in your blood that may be related to your disease).  
- You will be asked to have **additional** blood for correlative studies (optional) if you agree.  
We will further explain the optional blood studies at the end of this consent form.

If the exams, tests, and procedures show that you can be in the study, and you choose to take part, then you will begin study treatment as described below:
- You will receive doxorubicin (60-75 mg/m2 up to a total dose over time of 450 mg/m2) and pembrolizumab by IV (through a vein - intravenous) on Day 1 of each 21-day cycle. Your first dose of doxorubicin will be 60 mg/m2. If you tolerate that dose well, your next dose(s) may be increased to 75 mg/m2. This will be your study doctor's decision. If you are 18 years of age or older, you will receive 200 mg of pembrolizumab with each dose. If you are 12 to 17 years of age, the dose of pembrolizumab will be calculated from your weight (2 mg/kg, with a maximum dose of 200 mg).  
You will be given study treatment on 21-day cycles until the time your disease progresses, you are unable to tolerate the side effects of the study treatment, you decide you no longer wish to receive study treatment, or if your study doctor decides it is no longer in your best interest to receive study treatment. Your study doctor may discontinue the doxorubicin once you have received a specified number of doses but the pembrolizumab may continue as long as you are tolerating it and your disease is not worsening, but no longer than 24 months or after you have received 35 cycles, whichever comes first. If you are having unfavorable side effects, the study treatment may be stopped for a while, or the dose may be reduced. Your study doctor will also discuss with you whether it is in your best interest to continue study treatment. During the study, you will need the following exams, tests, and procedures. They are part of regular cancer care:
- Physical examination including vital signs and weight measurements. - You will be asked about the extent of your physical activity and how you are generally feeling.  
- CT scan (contrast dye preferred but not required) or MRI of the tumor site, chest, abdomen and pelvis every 6 weeks while you are receiving study treatment.  
- Blood work for blood counts and blood chemistry.  
- ECHO after every third dose of doxorubicin.  
The following tests and procedures will be done specifically for this study and are not part of your regular cancer care:
- Blood work for correlative (related) studies prior to every other cycle during your initial study treatment and also during the Second Course Phase (possible re-study treatment with pembrolizumab that some subjects may be eligible to participate in - please see the next page for more information) if you receive this.  
- You will be asked to have **additional** blood for correlative (related) studies (optional) prior to every other cycle during your initial study treatment and also during the Second Course Phase if you receive this. We will further explain the optional blood studies at the end of this consent form.  
- You will be asked to have a tumor biopsy (optional) anytime during your initial study treatment. We will further explain the optional tumor biopsy at the end of this consent form.

After you complete study treatment, you will have a post-study treatment safety follow-up visit. You will need the following exams, tests, and procedures. They are part of regular cancer care:
- Physical examination including vital signs and weight measurements. - You will be asked about the extent of your physical activity and how you are generally feeling.  
- CT scan or MRI of the tumor site, chest, abdomen and pelvis.  
- Heart monitoring:
o ECHO and ECG approximately 30 days after your last dose of doxorubicin. This may be required before the post-study treatment safety follow-up visit if you stop doxorubicin before you stop pembrolizumab The following tests and procedures will be done specifically for this study and are not part of your regular cancer care:
- Blood work for correlative (related) studies either at your end of study treatment visit or if your disease worsens.  
- You will be asked to have additional blood for correlative studies (optional) either at your end of study treatment visit or if your disease worsens

After you stop study treatment and have a post-study treatment safety follow-up visit, you will have additional post-study treatment follow-up visits to monitor your disease status until your disease  
worsens or you start new cancer treatment. Your disease status will be monitored per your study doctor's preference approximately every 9 weeks (+/- 7 days) for up to one year and then approximately every 12 weeks (+/- 7 days) unless your study doctor feels you need to have more frequent scans. You will also have periodic tests to monitor your heart as indicated below.
Clinical trial: NCT03056001
Section: Purpose of Research
Subsections: Why Is This Study Being Done?

The purpose of this study is to evaluate the safety, tolerability and efficacy of doxorubicin in combination with pembrolizumab in subjects with metastatic or unresectable soft tissue sarcoma. Based on previous studies, pembrolizumab may be an effective study treatment. Pembrolizumab has been approved by the Food and Drug Administration (FDA) in the United States for the treatment of a type of advanced skin cancer, melanoma, certain types of metastatic lung cancer (PD-L1+), and recurrent or metastatic squamous cell carcinoma of the head and neck. However, it has not been approved for the treatment of soft tissue sarcoma. Doxorubicin is an FDA-approved anticancer drug and is a standard chemotherapy used to treat soft tissue sarcoma.
Clinical trial: NCT03056001
Section: Voluntary Participation
Subsections: Atrium Health Consent To Participate In A Research Study For Subjects Who Turn 18 & Parental/Guardian Permission|Statement Of Consent|Statement Of Person Explaining Consent

Sponsor / Study Title:
Levine Cancer Institute / A Pilot Study Evaluating the Safety, Tolerability and Efficacy of Doxorubicin and Pembrolizumab in Patients with Metastatic or Unresectable Soft Tissue Sarcoma Protocol Number: LCI-SAR-STS-PEM-001  
Principal Investigator: Michael Livingston, MD  
Telephone: (24 Hours)  
  
Address: **Levine Cancer Institute**
If you are the parent or legal guardian of a child who may take part in this study, permission from you is required. The assent (agreement) of your child may also be required. When "you" appears in this form, it may refer to you or your child; "we" means the study doctors and study staff.

I have read this form and its contents were explained to me. I agree to be in this research study for the purposes listed above. All of my questions were answered to my satisfaction. I will receive a signed and dated copy of this form for my records. I am not giving up any of my legal rights by signing and dating this form. ___________________________ ____/____/____ _________  
  
 Signature of Research Subject (if subject is age 18 or older) Date Time ___________________________________ Printed Name of Research Subject _________________________________ Printed Name of Parent/Legal Guardian (if subject is under age 18)

I have carefully explained to the subject or the subject's parent/legal guardian the nature and purpose of the above study. There has been an opportunity for the subject or the subject's parent/legal guardian to ask questions about this research study. I have been available to answer any questions that the subject or the subject's parent/legal guardian has about this study.  
___________________________________ ____/____/____ _________  
  
 Signature of Person Explaining Consent Date Time
___________________________________  
  
Printed Name of Person Explaining Consent
___________________________ ____/____/____ _________  
  
 Signature of Parent/Legal Guardian (if subject is under age 18) Date Time
Clinical trial: NCT03056001
Section: Withdrawal from Study
Subsections: What If I Want To Quit The Study Later On?

Your participation in this study is completely voluntary. You should feel under no pressure to be in the study. If you decide not to be in the study, that will not in any way harm your relations with your doctors or with Atrium Health. You are free to stop being in the study if you change your mind after entering it. This would not harm your relations with your doctors or Atrium Health. Information contributed to the study will remain in the study even if you choose to withdraw. If you choose to withdraw from the study, please notify the study doctor in writing at: