Clinical trial: NCT00923936
Section: Alternatives
Subsections: Alternative Approaches Or Treatments|What Other Choices Do I Have If I Do Not Take Part In This Study?

People with advanced KS have several FDA approved therapy options for the management of advanced KS. These include liposomal daunorubicin, liposomal doxorubicin, or paclitaxel. Those who are HIV positive should be taking combination antiretroviral therapy. For patients with AIDS-associated KS who are not taking combination antiretroviral therapy at the time of diagnosis, additional therapy may be deferred to see if the KS improves with the treatment of HIV. However, this approach generally takes longer than approaches that incorporate chemotherapy, and may not be appropriate for people with advanced AIDS-associated KS.  
Patients with limited or mild KS may be treated with radiation therapy, interferon-α, injection of chemotherapy into the KS tumor, or topical treatments.  
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: 09-C-0130 CONTINUATION: page 7 of 14 pages 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.
Clinical trial: NCT00923936
Section: Confidentiality
Subsections: Will Your Medical Information Be Kept Private?

We will do our best to make sure that the personal information in your medical record will be kept private. However, we cannot guarantee total privacy. Organizations that may look at and/or copy your medical records for research, quality assurance, and data analysis include:  
- 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 Genentech, the pharmaceutical company who produces Bevacizumab.
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.  
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 Genentech 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  
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: 09-C-0130 CONTINUATION: page 11 of 14 pages 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.
Clinical trial: NCT00923936
Section: Duration of Study Involvement
Subsections: This Consent Document Has Been Approved For Use From March 13, 2017 Through **March 12, 2018.**

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: NCT00923936
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.
STUDY NUMBER: 09-C-0130 CONTINUATION: page 10 of 14 pages  
- 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: NCT00923936
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Risks Or Discomforts Of Participation|Less Likely (Less Than 10% Incidence), Continued|Rare But Serious|Potential Benefits Of Participation Are There Benefits To Taking Part In This Study?

What side effects or risks can I expect from being in this study? Likely (10% or greater incidence)
- Weakness
- Fever
- Hypertension
- Protein or blood in urine
- Mouth sores
- Nausea
- Nose bleed
- Low platelet counts (increased risk for bleeding)
- Low white blood cells (increased risk for infection)
- Anemia (low red blood cell counts, increased fatigue and mild shortness of breath)
- Infections
- Pain
- Discomfort from blood draws, catheter placement or biopsies Less Likely (less than 10% incidence)
- Diarrhea
- Vomiting - Dehydration
- Constipation
- Difficulty swallowing
- Weight loss  
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: 09-C-0130 CONTINUATION: page 8 of 14 pages
- Asymptomatic abnormalities in liver tests
- Gastrointestinal ulcers (esophagus, stomach, intestine, rectum or anus)
- Gum bleeding - Bleeding hemorrhoids
- Blood clots (thrombosis) in veins or arteries
- Abdominal swelling
- Leg swelling
- Pleural effusion (fluid collection between ribs and lungs) - Dizziness

- Anxiety, depression or panic attack
- Cough
- Herpes outbreak
- Hoarseness
- Kidney dysfunction
- Hair loss
- Rash
- Wound healing complications
- Hand and foot redness (hand-foot syndrome)
- Abnormalities in blood levels of sodium, calcium, potassium, and magnesium or glucose
- Muscle or joints aches
- Cataracts
- Increased tearing
- Elevation in the level of bilirubin (a waste product of the liver), may lead to jaundice or discolored urine

- Gastrointestinal perforation
- Fistula formation (abnormal hole or connection between organs)
- Peritonitis (inflammation or infection of the abdominal cavity)
- Hernias at sites of surgery - Bleeding from lungs, gastrointestinal tract, bladder or vagina
- Bleeding after surgical procedures
- Pancreatitis
- Liver Failure
- Bone marrow failure - Severely decreased red blood cells, white blood cells and platelets
- Severe hypertension with headaches, confusion or other neurological symptoms  
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: 09-C-0130 CONTINUATION: page 9 of 14 pages  
- Stroke
- Chest Pain / Heart Attack / Myocardial Infarction
- Pulmonary Embolism - Abnormalities in heart rhythm
- Acute pulmonary edema (shortness of breath due to fluid in the lungs)
- Heart failure
- Seizures, confusion, blindness (Reversible posterior leukoencephalopathy syndrome)
- Severe kidney dysfunction - Acute infusion reaction (pain, low blood pressure, difficulty breathing) - Death

The aim of this study is to see if this experimental combination of liposomal doxorubicin with bevacizumab followed by bevacizumab alone will cause your KS to shrink. We hope that you will get personal medical benefit from taking part in this study, but we cannot be certain. Because this study includes an effective FDA drug approved for KS, we expect that most participants will have some degree of tumor shrinkage while participating in this study. However, we do not know if the combination of liposomal doxorubicin with bevacizumab will be as good as or better than liposomal doxorubicin alone. We cannot predict whether you will benefit directly from taking part in this study, although the knowledge gained from this study may help others in the future who have cancer. Potential benefits could include shrinking of your KS or lessening of your symptoms, such as pain and swelling, which are caused by the cancer. Additionally, you may require less liposomal doxorubicin than usually needed through participation in this study.
Clinical trial: NCT00923936
Section: Procedures
Subsections: What Will Happen If You **Take Part In This Research Study?**

Before you begin the study, you will be evaluated by a physician investigator, as well as other members of the research team for eligibility in the study. We will discuss your medical history in detail and draw blood from a vein and collect a urine sample to determine your eligibility to participate in the study. A biopsy is required for participation. If you have already had a biopsy, we will work with you to have the biopsy sent to pathologists at the NCI for review. If you have not have not had a biopsy, we will arrange for a biopsy to confirm the diagnosis of KS. You will also undergo special tests of your heart as well as a chest X-ray to make sure that you are eligible to participate and to document whether KS affects your lungs. Additional studies may be required to document the extent of KS, depending on your symptoms. During the study, you will receive a single dose of bevacizumab followed one week later by both liposomal doxorubicin and bevacizumab every 3 weeks for 6 cycles. Patients with HIV will be required to be taking combination antiretroviral medications. All patients will be required to take a daily baby aspirin to prevent blood clots. During the first cycle, you will be evaluated by a physician prior to therapy, as well as one week later, to answer any questions you may have and to ensure that you are tolerating the therapy. On subsequent cycles, a physician will evaluate you on the day you receive therapy. After the first 6 cycles, you will receive bevacizumab alone. During each cycle, approximately 10 teaspoons of blood will be collected from a vein to be used for laboratory studies that are part of routine care for patients receiving therapy, as well as special research studies. Saliva will be collected during the first cycle, then every 3 cycles afterwards. We will also collect a urine sample every cycle to make sure that the therapy is not damaging your kidneys. If your KS completely disappears, you will be asked to repeat any abnormal tests that you had when you entered the study, including a biopsy. Optional tests will include an additional biopsy for special studies evaluating the effect of therapy on your KS tumor. Part of the evaluation will include measurement of your blood pressure. If your blood pressure is greater than 140/90 on two consecutive visits, you will be started on oral medications to control your blood pressure. After completing the 6 cycles of the combination of liposomal doxorubicin and bevacizumab, you will have a repeat evaluation of your heart.  
STUDY NUMBER: 09-C-0130 CONTINUATION: page 4 of 14 pages On this protocol, you will have periodic conventional photographs made of your lesions. Additionally, three experimental imaging methods will be performed. The three methods are called: 1) laser Doppler imaging, 2) multi-spectral imaging and, 3) infrared thermal imaging. Laser Doppler imaging takes about 3 minutes to perform on each lesion. It uses a low power laser beam that scans across the skin lesion being measured. The instrument does not touch your skin. You may be asked to have a blood pressure cuff put on your arm and have laser Doppler imaging performed before and after the cuff is inflated for a short time (generally less than thirty seconds). We do not believe that this instrument will harm your skin: in standard practice a similar machine is used to measure how deeply severe burns affect the skin. If you stare at a laser light it could harm your eyes, but precautions will be taken so that you will not stare at it. It is also used to assess allergic responses in the skin. However, its use in Kaposi's sarcoma is experimental. The purpose of this experimental use is to attempt to measure the amount of blood flow through the blood vessels in the Kaposi's sarcoma lesions. It will not have a therapeutic effect on the lesions. The multi-spectral imaging exam should take about 2 minutes to perform on each lesion. It uses principles of the way hemoglobin absorbs light. Hemoglobin is a protein in the blood that carries oxygen to your tissues. The light on the multi-spectral imaging instrument is absorbed differently depending on whether the hemoglobin has oxygen attached to it or not. This will allow an estimate to be made regarding the total blood volume, and how much of it is carrying oxygen or not. We do not believe that the instrument will harm you. The technique will not make your Kaposi's sarcoma improve. The thermal imaging takes about a minute to perform on each lesion. It uses a special camera to take digital infrared pictures of your skin. This enables us to form a picture of the temperature of your KS lesions and thus assess the blood flow in the Kaposi's sarcoma lesions. We do not believe that the camera and lights will harm you. These experimental imaging studies will be performed twice during the first cycle then repeated after the sixth cycle and after the last cycle of therapy. When you are finished taking the drugs, we will continue to follow you in clinic every 3 months for up to 2 years to make sure that your KS does not return or get worse. If the KS should get worse during the observation, a second course of therapy may be possible within the study, and we would discuss further treatment options with you.  
STUDY NUMBER: 09-C-0130 CONTINUATION: page 5 of 14 pages The following Study Chart outlines what will happen if you choose to participate.
Clinical trial: NCT00923936
Section: Purpose of Research
Subsections: Why Are You Being Asked To Take Part In This Study?|Description Of Research Study

Individuals may be eligible to participate in the research study if they have relatively severe AIDS-related Kaposi's sarcoma, or if they have Kaposi's sarcoma unrelated to AIDS or HIV infection. To be eligible for the trial, patient-volunteers must have KS that can be evaluated for potential response to therapy, and meet a number of other criteria. If you meet these criteria, you are being asked to take part in this study so that we may evaluate this novel combination of liposomal doxorubicin with bevacizumab in people, like yourself, with advanced KS.

If you consent to participate in this study, you will receive therapy through a vein (IV), starting with an initial dose, followed one week later by therapy every 3 weeks for one year. We will continue to follow you for up to 2 additional years to make sure that your KS does not worsen once therapy is stopped. If your KS worsens during the course of your participation in the study, you may be eligible for additional liposomal doxorubicin and/or bevacizumab within this study. The treatment for KS in this study will consist of two phases, an induction phase and a maintenance phase. The goal of the induction phase is to rapidly reduce your KS. During the induction phase, you will receive a single dose of bevacizumab followed by 6 cycles of the combination of liposomal doxorubicin and bevacizumab every 3 weeks. The goal of the maintenance phase is to attain further tumor shrinkage and prevent recurrences of KS, while minimizing the amount of liposomal doxorubicin used. In the maintenance phase, you will not receive liposomal doxorubicin, but will continue to receive bevacizumab every 3 weeks for a total of 1 year of therapy. If, during the first phase, you have no evidence of KS after fewer than 6 cycles, we will discontinue the liposomal doxorubicin, and proceed to the second phase of the study. During the study, we will also be collecting blood and saliva, performing non-invasive imaging studies of your KS for research purposes, and performing 1-3 biopsies both for routine purposes as well as special research into the biology of KS and the effect of the research medications on your body and on the KS tumors (biopsies for research alone are optional). A description of  
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: 09-C-0130 CONTINUATION: page 3 of 14 pages what will happen if you take part in this study, as well as a list of potential risks and discomforts associated with participation in the study are listed below. Due to a shortage of liposomal doxorubicin (brand name Doxil) in the United States, you may receive an alternate imported brand of liposomal doxorubicin (Lipodox). The FDA has approved the temporary use of Lipodox during the national shortage of Doxil.