Clinical trial: NCT04118166
Section: Alternatives
Subsections: We Cannot And Do Not Guarantee Or Promise That You Will Receive Any Benefits From This Study. Alternatives

If you choose not to participate in this study, there are several alternative treatments for your disease. They include:
Treatment with standard chemotherapy  
Investigational chemotherapy (other clinical trials) Supportive care. This type of care focuses on control of symptoms, pain relief and quality of life. It does not treat your cancer directly.
Clinical trial: NCT04118166
Section: Confidentiality
Subsections: Confidentiality|Authorization To Use Your Health Information For Research Purposes|What Personal Information Will Be Obtained, Used Or Disclosed?|Who May Use Or Disclose The Information?|Who May Receive Or Use The Information?|When Will My Authorization Expire?|Will Access To My Medical Record Be Limited During The Study?

Identifiers might be removed from identifiable private information and/or  
 identifiable specimens and, after such removal, the information and/or specimens could be used for future research studies or distributed to another  
  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma investigator for future research studies without additional informed consent from you. The results of this research study may be presented at scientific or medical meetings or published in scientific journals. Your identity and/or your personal health information will not be disclosed except as authorized by you or as required by law. However, there is always some risk that even de-identified information might be re-identified. Patient information may be provided to Federal and other regulatory agencies as required. The Food and Drug Administration (FDA), for example, may inspect research records and learn your identity if this study falls within its jurisdiction. The purpose of this research study is to obtain information on the safety and effectiveness of ipilimumab plus nivolumab in combination with cryotherapy; the results will be provided to Bristol-Myers Squibb, its affiliates, agents, and employees, the Food and Drug Administration and other federal and regulatory agencies as required.  
  
  
  
  
Expiration Date: August 12, 2021  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma

Because information about you and your health is personal and private, it generally cannot be used in this research study without your written authorization. If you sign this form, it will provide that authorization. The form is intended to inform you about how your health information will be used or disclosed in the study. Your information will only be used in accordance with this authorization form and the informed consent form and as required or allowed by law. Please read it carefully before signing it.

Your health information related to this study that may be used or disclosed in connection with this research study, includes but is not limited to, your hospital/doctor's office records including your medical history and physical exam records, genetic information, test results (such as x-rays or other imaging results, laboratory results, pathology results), your whole research record (including all records relating to your condition, the treatment you have received and your response to the treatment).

The following parties are authorized to use and/or disclose your health information in connection with this research study:  
The Protocol Director, Dr Kristen Ganjoo The Stanford University Administrative Panel on Human Subjects in Medical Research and any other unit of Stanford University as necessary Research Staff

The parties listed in the preceding paragraph may disclose your health information to the following persons and organizations for their use in connection with this research study:  
The Office for Human Research Protections in the U.S.  
  
Department of Health and Human Services  
  
  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma  
The funder of this study (Bristol-Myers Squibb) and its affiliates, agents, and employees Stanford Cancer Institute Innovation Award The Food and Drug Administration
Your information may be re-disclosed by the recipients described above, if they are not required by law to protect the privacy of the information.

Your authorization for the use and/or disclosure of your health information will end on December 31, 2068 or when the research project ends, whichever is earlier.

To maintain the integrity of this research study, you may not have access to any health information developed as part of this study until it is completed. At that point, you would have access to such health information if it was used to make a medical or billing decision about you (e.g., if included in your official medical record). ________________________________ ______________ Signature of Adult Participant Date
________________________________ Print Name of Adult Participant  
  
  
  
Approval Date: May 7, 2021 Expiration Date: August 12, 2021  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma
Clinical trial: NCT04118166
Section: Duration of Study Involvement
Subsections: Duration Of Study Involvement

If you agree to participate in this research study, before you receive study  
 treatment, you will undergo a screening period that will last approximately 28 days. If you are eligible for this study, you may continue to receive study treatment for up to 24 months, unless you have unacceptable side effects, you  
  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma withdraw your consent, your disease progresses, or the investigator feels that it is in your best interest to stop the study treatment. After you stop study treatment, you will have an off study visit within 30 days of your last dose of study drug. Thereafter, you will be contacted by study staff every 35 days, twice, to collect information on your health status. The entire study is expected to take 5 years, including time for data analysis. Data analysis will take approximately 1 year to complete. You will spend approximately 3-5 hours at the cancer center for each visit.  
These visits will be used for treatment, to collect information on your health and to obtain necessary bloodwork and tests. You may spend up to 23 hours at Stanford procedure facility when you receive cryotherapy.
Clinical trial: NCT04118166
Section: Participant Responsibilities
Subsections: _____ I Agree To Have The Optional Tumor Tissue Sampling|_____ I Consent To My Specimens Being Saved For Up To 30 Years For Future Research _____ I Do Not Consent To My Specimens Being Saved For Up To 30 Years For Future Research|Participant Responsibilities

______ **I do not agree to have the optional tumor tissue sampling**  
  
  
  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma The total amount of blood to be collected at this End of Treatment/Off Study Visit is approximately 6.5 teaspoons (tsp): Approximately 1.2 tsp (6 mL) for routine blood tests and approximately 5 tsp (25 mL) for research-related tests.

Specimen Sampling for Genetic Testing As part of the analysis on your specimens, the investigators will do genetic testing. Genetic research is research that studies genes, including gene characteristics and gene versions that are transmitted by parents to children. Genetic research may include looking at information, such as personal appearance and biochemistry, gene sequences, genetic landmarks, individual  
  
  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma and family medical histories, reactions to medications and responses to treatment. Genetic research raises certain questions about informing you of any results. Possible risks of knowing results include: anxiety; other psychological distress; and the possibility of insurance and job discrimination. A possible risk of not knowing includes being unaware of the need for treatment. These risks can change depending on the results of the research and whether there is a treatment or cure for a particular disease. Sometimes patients have been required to furnish information from genetic testing for health insurance, life insurance, and/or a job. A Federal law, the Genetic Information Nondiscrimination Act of 2008 (GINA), generally makes it illegal for health insurance companies, group health plans, and employers with 15 or more employees to discriminate against you based on your genetic information. The results of the study of your specimens from this project will be used for research purposes only, and you will not be told the results of the tests. Any of your specimens which are used in research may result in new products, tests or discoveries. In some instances, these may have potential commercial value and may be developed and owned by the Investigators, Stanford University and/or others. However, donors of specimens do not retain any property rights to the materials. Therefore, you would not share in any financial benefits from these products, tests or discoveries.

As a participant, your responsibilities include:
Follow the instructions of the Protocol Director and study staff.  
Take the study drug as instructed Keep your study appointments. If it is necessary to miss an appointment, please contact the Protocol Director or research study staff to reschedule as soon as you know you will miss the appointment.  
Tell the Protocol Director or research study staff about any side effects, doctor visits, or hospitalizations that you may have.  
Tell the Protocol Director or research staff if you believe you might be pregnant or gotten your partner pregnant.  
Ask questions as you think of them. Tell the Protocol Director or research staff if you change your mind about staying in the study.
Clinical trial: NCT04118166
Section: Participant's Rights
Subsections: Participant'S Rights|Experimental Subject'S Bill Of Rights

You should not feel obligated to agree to participate. Your questions should be answered clearly and to your satisfaction. If you decide not to participate, tell the Protocol Director. You will be told of any important new information that is learned during the course of this research study, which might affect your condition or your willingness to continue participation in this study.

As a research participant you have the following rights. These rights include but are not limited to the participant's right to:
be informed of the nature and purpose of the experiment;  
be given an explanation of the procedures to be followed in the medical experiment, and any drug or device to be utilized; be given a description of any attendant discomforts and risks reasonably to be expected; be given an explanation of any benefits to the subject reasonably to be expected, if applicable; be given a disclosure of any appropriate alternatives, drugs or devices that might be advantageous to the subject, their relative risks and benefits; be informed of the avenues of medical treatment, if any available to the subject after the experiment if complications should arise; be given an opportunity to ask questions concerning the experiment or the procedures involved; be instructed that consent to participate in the medical experiment may be withdrawn at any time and the subject may discontinue participation without prejudice; be given a copy of the signed and dated consent form; and be given the opportunity to decide to consent or not to consent to a medical experiment without the intervention of any element of force, fraud, deceit, duress, coercion or undue influence on the subject's decision.  
  
  
  
  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma May we contact you about future studies that may be of interest to you? ____ Yes ____ No Signing your name means you agree to be in this study and that you will receive a copy of this signed and dated consent form.  
_____________________________________ ____________  
 Signature of Adult Participant Date
_____________________________________ Print Name of Adult Participant _____________________________________ ____________ Signature of Person Obtaining Consent Date _____________________________________ Print Name of Person Obtaining Consent The following witness line is to be signed only if the consent is provided as a summary form and accompanied by a short form foreign language consent.  
_____________________________________ ____________  
  
 Signature of Witness Date
__________________________________ Print Name of Witness
(e.g., staff, translator/interpreter, family member)  
Translated short form must be signed and dated by both the participant (or their LAR) AND the witness.  
The English consent form (referred to as the "Summary Form" in the regulations):
Must be signed by the witness AND the Person Obtaining Consent (POC).  
The non-English speaking participant/LAR does not sign the English consent.  
The non-English speaking participant/LAR should not sign the HIPAA participant line If the participant or the LAR is non-English speaking, the Person Obtaining Consent
(POC) must ensure that 1) the LAR's Description of Authority is completed and 2)
that any questions or options presented by the consent form are documented and initialed by the POC on the Summary Form, per the participant's wishes, as they are understood during the consent process.
Clinical trial: NCT04118166
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Possible Risks, Discomforts, And Inconveniences|Nivolumab Side Effects|Common (Occurring In More Than 20% Of Patients)|Ipilimumab Side Effects Common (Occurring In More Than 20% Of Patients)|Occasional (Occurring In 3-20% Of Patients)|Rare But Serious (Occurring In Fewer Than 3% Of Patients)|Ct Scan Risks:|Mri (Magnetic Resonance Imaging):|Risks:|If You Feel Discomfort At Any Time, Notify The Operator And You Can Discontinue The Exam At Any Time. Non-Physical Risks:|Pregnancy Related Risks:

There are risks, discomforts, and inconveniences associated with any research study. These deserve careful thought. You should talk with the Protocol Director if you have any questions. Your cancer may not improve or may worsen during your participation in this study. While receiving the study treatment, you may have side effects. These side effects will vary from person to person. The more commonly occurring side effects are listed in this form, as are rare, but serious, side effects. You should discuss these with the study doctor. You may also want to ask about uncommon side effects that have been observed in small numbers of patients but are not listed in this form. Many side effects go away shortly after treatment is stopped, but in some cases side effects may be serious, long-lasting or permanent, and may even result in hospitalization and/or death. There may be additional risks that are unknown or unexpected.  
  
  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma Tell the study staff about any side effects you may have, even if you do not think they are related to the study drug/procedures. Nivolumab and ipilimumab may each cause low blood cell counts (red blood cells, platelets, and/or white blood cells):  
A low red blood cell count (anemia) may cause difficulty breathing and/or fatigue. You may need a blood transfusion.  
A low platelet count increases your risk of bleeding (such as nosebleeds, bruising, stroke, and/or digestive system bleeding). You may need a platelet transfusion.  
A low white blood cell count increases your risk of infection (such as pneumonia and/or severe blood infection). Infections may occur anywhere and become life-threatening. Symptoms of infection may include fever, pain, redness, and difficulty breathing.

|    | fatigue/lack of energy                                                                                                                                                                           |    |                                                                    |
|-----|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----|--------------------------------------------------------------------|
|    | fever                                                                                                                                                                                            |    |                                                                    |
|    | skin rash                                                                                                                                                                                        |    |                                                                    |
|    | itching                                                                                                                                                                                          |    |                                                                    |
|    | abnormal salts,  minerals, and/or  acids in the blood  (possible weakness,  swelling, fatigue, low  blood pressure, organ  failure, heart  problems, changes in  mental status, and/or  seizure) |   | high blood levels of  fat (possible heart  disease and/or  stroke) |
|    | high blood sugar  (possible diabetes)                                                                                                                                                            |    |                                                                    |
|    | diarrhea                                                                                                                                                                                         |    |                                                                    |
|    | loss of appetite                                                                                                                                                                                 |    |                                                                    |
|    | nausea                                                                                                                                                                                           |    |                                                                    |
|    | constipation                                                                                                                                                                                     |    |                                                                    |
|    | abnormal digestive  blood test (possible  inflammation of the  pancreas)                                                                                                                         |   | low blood cell counts  (red, white, platelets)                     |
|    | abnormal liver test  (possible liver  damage and/or  yellowing of the skin  and/or eyes)                                                                                                         |    |                                                                    |
|    | pain                                                                                                                                                                                             |    |                                                                    |
|    | abnormal kidney test  (possible kidney damage)                                                                                                                                                   |    |                                                                    |
|    | weakness                                                                                                                                                                                         |    |                                                                    |
|    | difficulty breathing                                                                                                                                                                             |    |                                                                    |
|    | cough                                                                                                                                                                                            |    |                                                                    |
|    | infection                                                                                                                                                                                        |    |                                                                    |

Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma  
| Occasional (occurring in 3-20% of patients)               |                                                                                                                        |    |                                                                                                        |
|-----------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------|----|--------------------------------------------------------------------------------------------------------|
|                                                          | swelling (arm/leg)                                                                                                     |    |                                                                                                        |
|                                                          | headache                                                                                                               |    |                                                                                                        |
|                                                          | skin redness                                                                                                           |    |                                                                                                        |
|                                                          | patches of skin color  loss                                                                                            |    |                                                                                                        |
|                                                          | very severe blistering  skin disease (loss of  large portion of skin  and/or ulcers of the  skin and digestive  tract) |    |                                                                                                        |
|                                                          | overactive thyroid  gland (possible  weight loss, heart  rate changes, and/or  sweating)                               |    |                                                                                                        |
|                                                          | underactive thyroid  gland (possible  weight gain, heart  failure, and/or  constipation)                               |    |                                                                                                        |
|                                                          | inflammation of the  thyroid gland  (possible tenderness  in the neck)                                                 |    |                                                                                                        |
|                                                          | vomiting                                                                                                               |   | abdominal pain                                                                                         |
|                                                          | inflammation of the  intestines                                                                                        |    |                                                                                                        |
|                                                          | hole in the intestines  (possibly leaking  contents into the  abdomen)                                                 |    |                                                                                                        |
|                                                          | mouth blisters/sores  (possible difficulty  swallowing)                                                                |    |                                                                                                        |
|                                                          | abnormal blood test  (possible pancreas  damage)                                                                       |    |                                                                                                        |
|                                                          | nerve damage  (possible numbness,  pain, and/or loss of  motor/sensory  function)                                      |    |                                                                                                        |
|                                                          | inflammation of  nerves (possible pain  and/or loss of motor  or sensory function)                                     |   | muscle damage  causing weakness                                                                        |
|                                                          | joint disease                                                                                                          |    |                                                                                                        |
|                                                          | build-up of fluid  around the lungs                                                                                    |    |                                                                                                        |
|                                                          | lung inflammation  (possible difficulty  breathing)                                                                    |    |                                                                                                        |
|                                                          | stuffy nose                                                                                                            |    |                                                                                                        |
|                                                          | immune reaction  (possible organ  damage)                                                                              |    |                                                                                                        |
|                                                          | immune system  disease (possible dry  mouth/eyes, fatigue,  joint pain, and/or  organ failure)                         |    |                                                                                                        |
|                                                          | infusion reaction  (possible chills and/or  hives)                                                                     |    |                                                                                                        |
| Rare but serious (occurring in fewer than 3% of patients) |                                                                                                                        |    |                                                                                                        |
|                                                          | blood vessel  inflammation  (possible bleeding  and/or bruising)                                                       |    |                                                                                                        |
|                                                          | heart inflammation                                                                                                     |    |                                                                                                        |
|                                                          | brain inflammation  (possible paralysis  and/or coma)                                                                  |    |                                                                                                        |
|                                                          | damage to the  nervous system  (causing numbness                                                                       |   | hormonal deficiency  that affects the  body's ability to  control blood  pressure and react to  stress |
|                                                          | inflammation of the  pancreas (possible  abdominal pain)                                                               |    |                                                                                                        |
|                                                          | liver damage  (possibly due to                                                                                         |   | blockage in the lung  (possible pain and/or  shortness of breath)                                      |
|                                                          | multi-organ disease  causing lesions, most  often in the lungs  (sarcoidosis)                                          |    |                                                                                                        |
|                                                          | severe  life-threatening  infection (possible  low blood pressure,                                                     |    |                                                                                                        |  
  
  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma  
| and/or paralysis)   |                                                                                                                              |                                        |                                                                                               |             |
|---------------------|------------------------------------------------------------------------------------------------------------------------------|----------------------------------------|-----------------------------------------------------------------------------------------------|-------------|
|                    | paralysis of nerves  controlling the head  and neck                                                                          |                                        |                                                                                               |             |
|                    | diabetes requiring  insulin                                                                                                  |                                        |                                                                                               |             |
|                    | severe high blood  sugar due to  uncontrolled diabetes                                                                       | blood clots)                           |                                                                                               |             |
|                    | paralysis (face)                                                                                                             |                                        |                                                                                               |             |
|                    | uncontrolled  movements                                                                                                      |                                        |                                                                                               |             |
|                    | inflammation inside  the eye (possible  vision problems)                                                                     |                                        |                                                                                               |             |
|                    | kidney failure                                                                                                               |                                        |                                                                                               |             |
|                    | breakdown of muscle  tissue (possible  kidney failure)                                                                       | kidney failure, and/or  heart failure) |                                                                                               |             |
|                    | Vogt Koyanagi  Harada syndrome -- pigmented tissue  (possible eye  pain/swelling, hearing  loss, and/or loss of  skin color) |                                        |                                                                                               |             |
|                    | Muscle inflammation                                                                                                          |                                        |                                                                                               |             |
| Frequency unknown   |                                                                                                                              |                                        |                                                                                               |             |
|                    | migraine                                                                                                                     |                                       | hand-foot syndrome  (palms of hands/soles  of feet having pain,  swelling, and  blistering)  | weight loss |  
You may need to take drugs to reduce inflammation while taking nivolumab. Long-term use of these drugs may increase your risk of infection. These infections may occur anywhere and may be fatal. Treatment with antibiotic or antifungal drugs may be required to treat these infections. The study drug works by boosting the immune system. This may cause unknown side effects resulting from your immune system attacking your organs. This may cause inflammation and inflammation-related side effects in any organ or tissue. Nivolumab may cause serious side effects that affect your immune system. Some of these side effects start as inflammation in different areas of the body like the skin, hormone glands, pancreas, or appendix. Tell the study staff right away if you have diarrhea, nausea, vomiting, blurred vision, dizziness, fainting, or you are feeling cold all the time. If you have a stem cell transplant from a donor before or after you receive nivolumab, you may have an increased risk of complications, such as severe graft-versus-host disease (when transplanted donor tissue attacks the recipient's organs such as skin, liver, and/or intestines) and/or clotting of blood within the liver. Deaths have been reported in patients who received stem cell transplant from a donor before or after nivolumab therapy. If you decide to receive a stem  
  
  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma cell transplant from a donor, please tell your transplant doctor that you received nivolumab in the past. If you had an organ transplant, nivolumab may increase your risk for the transplant to be rejected by your body.

|    | fatigue                                                                  |    |                  |
|-----|--------------------------------------------------------------------------|----|------------------|
|    | headache                                                                 |    |                  |
|    | itching and/or skin  rash                                                |    |                  |
|    | weight loss                                                              |    |                  |
|    | nausea                                                                   |    |                  |
|    | diarrhea                                                                 |   | loss of appetite |
|    | vomiting                                                                 |    |                  |
|    | abnormal digestive  blood test (possible  inflammation of the  pancreas) |   | constipation     |
|    | low red blood cell  counts                                               |    |                  |
|    | abnormal liver tests  (possible liver  damage)                           |    |                  |

|    | fever                                                                                |    |                                                                     |
|-----|--------------------------------------------------------------------------------------|----|---------------------------------------------------------------------|
|    | difficulty sleeping                                                                  |    |                                                                     |
|    | death of skin tissue  and skin sores                                                 |    |                                                                     |
|    | very severe blistering  skin disease (with  loss of large portion  of skin)          |    |                                                                     |
|    | very severe blistering  skin disease (with  ulcers of the skin and  digestive tract) |   | skin rash with blisters  or bleeding                                |
|    | pituitary gland failure  (possible endocrine  gland abnormality)                     |    |                                                                     |
|    | abdominal pain                                                                       |    |                                                                     |
|    | inflammation of the  intestines                                                      |    |                                                                     |
|    | abnormal blood test  (possible pancreas  damage)                                     |   | abnormal liver tests  (possible yellowing of  the skin and/or eyes) |
|    | liver damage                                                                         |    |                                                                     |
|    | abnormal kidney test  (possible kidney  damage)                                      |    |                                                                     |
|    | cough                                                                                |    |                                                                     |
|    | difficulty breathing                                                                 |    |                                                                     |  
  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma

|    | blood vessel disease                                                                                      |    |                                                                                         |
|-----|-----------------------------------------------------------------------------------------------------------|----|-----------------------------------------------------------------------------------------|
|    | blood vessel inflammation  (possible bleeding and/or  bruising)                                           |    |                                                                                         |
|    | leakage of fluids from  blood vessels into  surrounding tissue  (possible difficulty  breathing)          |    |                                                                                         |
|    | heart inflammation                                                                                        |    |                                                                                         |
|    | inflammation of the tissue  around the heart  (possible chest pain)                                       |    |                                                                                         |
|    | cardiac arrest                                                                                            |    |                                                                                         |
|    | cardiopulmonary failure  (failure of heart and  lungs)                                                    |    |                                                                                         |
|    | syncope (fainting)                                                                                        |    |                                                                                         |
|    | brain inflammation  (possible paralysis and/or  coma)                                                     |    |                                                                                         |
|    | immune system damage  to the nervous system  (causing numbness  and/or paralysis)                         |    |                                                                                         |
|    | immune response  (causing muscle  weakness)                                                               |    |                                                                                         |
|    | nerve damage (loss of  motor or sensory  function)                                                        |    |                                                                                         |
|    | Cushing's syndrome  (possible weakness,  diabetes, and/or bone  weakness)                                 |    |                                                                                         |
|    | red, dry, scaly patches of  thickened skin (psoriasis)                                                    |   | overactive thyroid gland  (possible weight loss,  heart rate changes,  and/or sweating) |
|    | underactive thyroid  gland (possible weight  gain, heart failure,  and/or constipation)                   |    |                                                                                         |
|    | hypophysitis  (inflammation of the  pituitary gland)                                                      |    |                                                                                         |
|    | hole in the intestines  (possibly leaking  contents into the  abdomen)                                    |    |                                                                                         |
|    | inflammation of the  pancreas (possible  abdominal pain)                                                  |    |                                                                                         |
|    | stomach and/or small  intestine ulcer                                                                     |    |                                                                                         |
|    | colitis, ulcerative (large  intestine ulcer)                                                              |    |                                                                                         |
|    | diarrhea                                                                                                  |    |                                                                                         |
|    | enterocolitis  (inflammation of the  intestinal tract)                                                    |    |                                                                                         |
|    | ileus, paralytic  (condition where  intestine stops moving)                                               |    |                                                                                         |
|    | intestinal ischemia (lack  of blood flow to the  intestines)                                              |    |                                                                                         |
|    | anemia due to  destruction of red blood  cells                                                            |    |                                                                                         |
|    | bone marrow failure  due to abnormal tissue  growth                                                       |   | myasthenia gravis (disorder  of the nervous system  causing paralysis)                  |
|    | inflammation inside the eye  (possible vision problems)                                                   |    |                                                                                         |
|    | partial hearing loss                                                                                      |    |                                                                                         |
|    | kidney failure                                                                                            |    |                                                                                         |
|    | acute glomerulonephritis  (inflammation of the  kidney)                                                   |    |                                                                                         |
|    | dyspnea (shortness of  breath)                                                                            |    |                                                                                         |
|    | acute respiratory distress  syndrome (lung damage)                                                        |    |                                                                                         |
|    | pneumonitis (inflammation  of lungs)                                                                      |    |                                                                                         |
|    | respiratory distress  (breathing difficulty)                                                              |    |                                                                                         |
|    | respiratory failure (unable  to breathe)                                                                  |    |                                                                                         |
|    | bronchiolitis obliterans  (damage of the small  airways with difficulty  breathing)                       |    |                                                                                         |
|    | hypovolemic shock (lack of  blood circulation)                                                            |    |                                                                                         |
|    | multi-organ disease causing  lesions, most often in the  lungs (sarcoidosis)                              |    |                                                                                         |
|    | severe life-threatening  infection (possible low  blood pressure, kidney  failure, and/or heart  failure) |    |                                                                                         |
|    | immune response                                                                                           |    |                                                                                         |
|    | infection                                                                                                 |    |                                                                                         |
|    | colon gangrene (damage to  colon from infection)                                                          |    |                                                                                         |  
  
  
  
  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma  
  
|    | skin rash (possible  fever/lymph node  swelling/inflammation of  internal organs/abnormal  blood cell counts)   |    |                                                             |
|-----|-----------------------------------------------------------------------------------------------------------------|----|-------------------------------------------------------------|
|    | allergic skin reaction                                                                                          |    |                                                             |
|    | inflammation of the  thyroid gland (possible  tenderness in the neck)                                           |    |                                                             |
|    | decreased production of  adrenal hormones  (possible weakness  and/or low blood  pressure)                      |   | acute myeloid leukemia  (cancer of the blood)               |
|    | tumor hemorrhage  (tumor bleeding)                                                                              |    |                                                             |
|    | hematuria (blood in the  urine)                                                                                 |    |                                                             |
|    | liver failure                                                                                                   |    |                                                             |
|    | liver damage due to  inflammation                                                                               |    |                                                             |
|    | drug-induced liver injury                                                                                       |    |                                                             |
|    | liver function abnormal                                                                                         |    |                                                             |
|    | muscle inflammation  and weakness                                                                               |   | agranulocytosis (condition  of low white blood cell  count) |
|    | white blood cell disorder  (abnormal white cells)                                                               |    |                                                             |
|    | dehydration                                                                                                     |    |                                                             |
|    | hypokalemia (low blood  potassium)                                                                              |    |                                                             |
|    | hyperkalemia (high blood  potassium)                                                                            |    |                                                             |
|    | hyponatremia (low blood  sodium)                                                                                |    |                                                             |
|    | prostatitis (inflammation of  the prostate gland)                                                               |    |                                                             |  
Ipilimumab may cause dehydration that may be severe enough to require hospitalization. Ipilimumab may cause an increased risk of infection, such as pneumonia. This infection may occur anywhere (such as the brain/spinal cord, lungs, and/or blood). It may become life-threatening. Symptoms of infection may include fever, pain, redness, and difficulty breathing. Ipilimumab works by boosting the immune system. This may cause unknown side effects resulting from your immune system attacking your organs. This may cause inflammation and inflammation-related side effects in any organ or tissue. Using the study drugs together may cause side effects that are not seen when each is given alone. The study drug combination may also increase the frequency and/or severity of the side effects listed above. Risks Associated With Cryotherapy: Risks associated with cryotherapy include bleeding, infection, lung collapse (pneumothorax), and injury to blood vessels or other organs close to the area of cryotherapy. With any procedure there is a small risk of death. Blood Draw Risks: You may feel some discomfort when the blood samples are  
 drawn. Sometimes a bruise may develop where the blood was drawn or the needle was placed, and occasionally, infection or bleeding may develop at the  
  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma puncture site. There is a rare possibility that you will faint while having blood drawn or that nerve damage will occur. Tumor Biopsy Risks: The study requires 1 mandatory tumor **biopsy and** optional tumor biopsies that would not otherwise be part of your regular cancer care. These biopsies may cause discomfort, pain, bruising, bleeding, low blood pressure, scarring, swelling and/or infection at the site of the biopsy, and rarely, death. An allergic reaction to the anesthetic may occur. ECG Risks: The tape used to adhere the electrodes to your skin may cause some redness and/or swelling.

Radiation risks: This research study involves exposure to radiation from CT scan. This radiation exposure is not necessary for your medical care and is for research purposes only. The additional amount of radiation exposure is about 12.5 mSv, which is approximately equal to 25% of the limit that radiation workers (for example, a hospital x-ray technician) are allowed to receive in one year. This amount of radiation involves minimal risk and is necessary to obtain the research information desired.  
Contrast: There is a slight risk of developing an allergic reaction to the contrast material. The reaction can be mild (itching, rash) or severe (difficulty breathing or sudden shock). Death resulting from an allergic reaction is rare. Most reactions can be controlled using drugs. Be sure to tell your doctor if you have allergies of any kind (such as hay fever, iodine allergy, eczema, hives, or food allergies).
The contrast material used during CT scanning can cause water loss or damage to the kidneys that may lead to kidney failure. This is a concern if you have poor kidney function, dehydration, or diabetes, especially if you take Metformin® (Glucophage) to control diabetes.  
You may also experience discomfort related to lying still in an enclosed  
  
space for a prolonged period of time.

MRI machines use a strong magnet and radiofrequency magnetic fields to make images of the body interior. The scanning procedure is very much like an X-ray or  
  
  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma CT scan. You will be asked to lie on a long narrow couch for a certain amount of time while the machine gathers information. During this time you will not be exposed to x-rays, but rather a strong magnetic field and radiofrequency magnetic fields, which you will not feel. You will, however, hear repetitive tapping noises that arise from the Magnetic Resonance scanner. We will provide earplugs or headphones that you will be required to wear. The space within the large magnet in which you lie is somewhat confined, although we have taken many steps to relieve the "claustrophobic" feeling.

Magnetic fields do not cause harmful effects at the levels used in the MRI machine. However, the MR scanner uses a very strong magnet that will attract some metals and affect some electronic devices. If you have a cardiac pacemaker or any other biomedical device in or on your body, it is very important that you tell the operator/investigator immediately. As metallic objects may experience a strong attraction to the magnet, it is also very important that you notify the operator of any metal objects (especially surgical clips), devices, or implants that are in or on your body before entering the magnet room. All such objects must be removed (if possible) before entering the magnet room. In some cases, having those devices means you should not have an MRI scan performed. In addition, watches and credit cards should also be removed as these could be damaged. You will be provided a way to secure these items. If you have any history of head or eye injury involving metal fragments, if you have ever worked in a metal shop, or if you could be pregnant, you should notify the operator/investigator. You should also notify the operator/investigator if you have any tattoos on your body, including eyeliner and other permanent makeup. Tattoos could become warm and irritated during the scan and remain so for several days. If you would prefer not to participate in the MR scan due to the presence of tattoos on your body, please inform a research team member. There is a possibility that you will experience a localized twitching sensation due to the magnetic field changes during the scan. This is not unexpected and should not be painful. However, you may have the scan stopped at any time if this occurs. If you have had a previous reaction to Gadolinium-based contrast agents or a  
 history of severe allergies, please notify the operator/investigator. If you have kidney problems, please tell the operator.  
  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma It has been observed that deposits of Gadolinium-based contrast agent (GBCA) remain in the brains of some people who undergo four or more contrast enhanced MRI scans, long after the last administration. It is not yet known whether these Gadolinium deposits are harmful or can lead to adverse health effects. You should talk to the study doctor if you have any questions about the use of GBCAs with MRIs.

Your work schedule may be disrupted or you may be unable to work while on this study because of side effects or the time required for study-related activities.

Taking part in this study can result in risks to an unborn or breastfeeding baby, so you should not become pregnant, breastfeed a baby, or father a child while on this study. You must use birth control during the study if you are sexually active. Birth Control Specifications If you can become pregnant or father a child, you must use highly effective methods of birth control while on this study and for 5 months (women) or 7 months (men) after your last dose of study drug. Examples of highly effective methods of birth control include:  
condoms diaphragms cervical cap an intrauterine device (IUD)
surgical sterility (tubal ligation or vasectomy by you or your partner)  
birth control pills  
  
Males: Do not donate sperm while you are on study and for 7 months after the last dose of study drug. You should inform your partner of the potential harm to  
  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma an unborn child. Tell the doctor right away if your partner becomes pregnant or suspects pregnancy. If your partner/spouse becomes pregnant while you are on this study, the sponsor would like to collect information about the pregnancy. The study sponsor's contact information will be made available so that, if you and your partner wish to, you can share information about the outcome of the pregnancy with the sponsor. If you and/or your partner choose not to share this information, it will not result in any penalty or loss of benefits to which you are otherwise entitled.  
Females: If you are pregnant, you will not be enrolled on this study. If you become pregnant or suspect that you are pregnant, you must stop treatment immediately, and tell your doctor right away. The sponsor will ask for information about the pregnancy. Do not breast feed during the treatment period , and do not donate eggs (ova, oocytes) during the treatment period and for at least 5 months after the last dose of study treatment. Getting pregnant will result in your removal from this study. If you experience any of the adverse effects listed above or any changes in your health, please tell your study doctor immediately without waiting until the next planned study visit. You can contact Dr Kristen Ganjoo at 650-725-6413. You may contact an oncology doctor 24 hours a day by telephone at 650-498-6000. You should also tell your regular doctors. If there is an emergency and you need immediate assistance, please go to the emergency room (ER).  
  
IRB Use Only  
  
Approval Date: May 7, 2021 Expiration Date: August 12, 2021  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma
Clinical trial: NCT04118166
Section: Procedures
Subsections: Procedures The Immune System And Checkpoint Inhibitors:|Study Evaluations|What Will Happen To Me In This Study?|Blood Samples:|Research-Related Tests|O Tumor Biopsy|O Your Blood Will Be Collected For Research-Related Tests To Evaluate The Effect Of Immunotherapy On Your Tumor. Screening:|Treatment Plan:|Cycle 1 (Week 1)|Between Cycle 1 And Cycle 2 Cryotherapy|Cycle 2 (Week 4)|Cycle 3 (Week 7)|Cycle 4 (Week 10)|Day 1 Of Cycle 5 Through Cycle 21 - Maintenance Nivolumab|End Of Treatment/Off Study Visit (Within 30 Days Of The Last Time You Receive Study Drug)|Specimen Sampling For Research

The immune system has the ability to tell the difference between normal or healthy cells and those that are abnormal or "foreign," and it has the ability to attack the abnormal cells in order to defend against things like infection and disease, including cancer. The immune system also has multiple checkpoints to prevent healthy cells from being inappropriately attacked and destroyed by the immune system. Tumor cells often take advantage of these checkpoints to evade detection. Two such checkpoints are PD-1 and CTLA-4. PD-1 checkpoint protein on immune cells called T cells can tell the immune system that a cell is normal or healthy. PD-1 does this when its receptor attaches to another protein on normal cells. When it attaches, it tells the immune system that the other cell is normal or healthy, causing inactivation of the T cell so the immune system does not attack the normal cell. If a cancerous cell has this same type of protein on its surface, it may be able to bind to the PD-1 receptor, causing inactivation of the T cell, and thus evade detection by the immune system. This can lead to fewer active T cells that are able to fight your cancer. CTLA-4 is a checkpoint protein, which is on immune cells called T cells. CTLA-4 normally acts to downregulate the immune response so that it is not too active.  
  
  
  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma

If you choose to participate, the Protocol Director, Dr Kristen Ganjoo, and her research study staff will ask you to have screening tests, examinations, or procedures to find out if you are eligible to be in this research study. If you have had them recently, they may not need to be repeated. This will be up to the study doctor. After completing these screening tests, your doctor will determine whether you are eligible to participate in this study. If you do not meet the eligibility requirements, you cannot take part in this study. Your doctor will inform you of other options that are available to you. In some cases, you may be asked to have additional tests or examinations. For example, this can happen if an unexpected medical event occurs during the study.

During the study you will have testing done to check your health and effects of the study treatment. Each study visit may include some or all of the following tests/procedures.  
**Medical History Review** - A review of your medical history, including your cancer history and other cancer treatments you have received.  
**Medication Review** - A review of any medications you are taking now or have recently taken, including any over-the-counter medications.  
**Physical Exam and Vital Signs** - A complete physical exam including vital signs (temperature, heart rate, respiratory rate, blood pressure, height and weight). Height will only be obtained at screening visit.  
**Performance Status** - You will be asked about your ability to perform everyday tasks.

o **Routine blood tests (chemistry and hematology tests).**  
  
Your blood will be collected to evaluate your blood cell counts, kidney and liver function, electrolyte levels, and your blood's ability to clot (coagulation).  
  
  
Expiration Date: August 12, 2021  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma o **Other blood tests, as appropriate** - ACTH, serum cortisol, TSH,
fT4, CRP high sensitivity, and ESR. These tests will be done at screening, Cycle 1 (Week 1), and Cycle 2 (Week 4). They may also be done at other visits if you develop any symptoms of hormone insufficiency.  
**Electrocardiogram (ECG)** - to check your heart. This will be done at screening. An ECG may also be done at other visits if your study doctor thinks it is necessary.  
**Tumor Imaging/Measurements** - The status of your cancer will be evaluated by computed tomography (CT) scan or Magnetic Resonance Imaging (MRI).  
**Pregnancy Test** - If you are a woman who is able to have children, a pregnancy test will be done (blood).  
**Patient Questionnaire** - You will be asked to complete a questionnaire at each study visit before any assessments are performed. The questionnaire will ask you how you are feeling and about any side effects you may experience.

o **Archival tumor tissue sample** - An archival tumor sample will be sent to Stanford University. If you do not have an archival tumor sample, you will have a biopsy to collect a tumor tissue sample in order to take part in this study.

A tissue sample of your tumor will be obtained in between Cycle 1 and Cycle 2 immediately before cryotherapy at the time of your procedure. You may decline this biopsy. However, if you decline the biopsy, you will not be able to participate in this study.  
If feasible a tissue sample will also be obtained after  
  
completion of study treatment. This is optional. You may still participate in the study whether or not you agree to have this tumor biopsy collected.  
  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma  
A tissue sample from your tumor may be taken if you undergo medical procedures while on the study. This is optional. You may still participate in the study whether or not you agree to have this tumor biopsy collected.

If you choose to participate, and sign this informed consent, the following tests and procedures will be done during the screening visit:
Medical History Review  
Medication Review
Physical Exam and Vital Signs, and height  
Performance Status Patient Questionnaire Blood Samples:
o Routine blood tests (chemistry and hematology tests). o Pregnancy Test (if you are female and able to become pregnant) o Other blood tests: ACTH, serum cortisol, TSH, fT4, CRP, and ESR.  
Electrocardiogram (ECG)
Tumor Imaging/Measurements (CT or MRI scan)  
Research-related tests o Tumor tissue sample - An archival tumor sample will be sent to Stanford University. If you do not have an archival tumor sample, you will have a biopsy to collect a tumor tissue sample in order to take part in this study.  
o Blood sample - Your blood will be collected for research-related  
  
tests to evaluate the effect of immunotherapy on your tumor  
  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma The total amount of blood to be collected at this screening visit is approximately 8 teaspoons (tsp): Approximately 1.4 tsp (7 mL) for routine blood tests plus pregnancy test and approximately 1.5 tsp (7.5 mL) for Other blood tests and approximately 5 tsp (25 mL) for research-related tests. All research-related blood samples will be sent to Stanford University for analysis. Any samples left over after analysis will be destroyed when the study is completed.

If you are eligible for this study and you choose to take part, you will begin treatment. The study treatment is given in cycles. Cycles 1 through 4 are each 3 weeks (21 days) long. Cycles 5 and beyond are 4 weeks (28 days) long. You may receive study treatment for up to 24 months, unless you have unacceptable side effects, you withdraw your consent, your disease progresses, or the investigator feels that it is in your best interest to stop the study treatment. Study Drugs: The study drugs (ipilimumab and nivolumab) will be given intravenously (into your vein). Ipilimumab and nivolumab will be given as intravenous infusions over 2 hours every 3 weeks for 4 doses (= 4 cycles). Then, starting with Cycle 5, nivolumab will be given as an intravenous infusion over 1 hour every 4 weeks. Depending on whether you have a reaction during or after the infusion (some people experience allergic-type symptoms), additional medication may be given to prevent allergic reaction. If you have an allergic reaction during or after your infusion, you will be monitored for a period of time after the infusion. Cryotherapy: Between Cycle 1 and Cycle 2, you will receive cryotherapy. You may receive additional cryotherapy if your study doctor thinks it may be of benefit to you. Cryotherapy is a procedure that uses extreme cold to kill cancer cells. During cryotherapy, a needle probe will be inserted into your tumor using CT guidance, and a gas will be released from the probe that freezes cells in the treatment area. The tissue is then allowed to thaw. This process can be repeated in several times in the same treatment session. Cryotherapy will be done under sedation or general anesthesia depending on the location of your tumor. In most circumstances, you can expect to be discharged to home within 23 hours.  
  
  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma The following assessments and procedures will be performed during the treatment phase of the study:

Medication Review  
Physical Exam, Vital Signs, Height and Weight Performance Status Patient Questionnaire Side Effect Review Blood Samples o Routine blood tests (chemistry and hematology tests)
o Research blood tests o Pregnancy Test (if you are female and able to become pregnant)
o Other blood tests: ACTH, serum cortisol, TSH, fT4, CRP, and ESR.  
Tumor Imaging/Measurements again reviewed You will receive the study drugs for the first time in outpatient infusion room.
The total amount of blood to be collected at this Cycle 1 (Week 1) visit is approximately 8 teaspoons (tsp): Approximately 1.4 tsp (7 mL) for routine blood tests plus pregnancy test and approximately 1.5 tsp (7.5 mL) for Other blood tests and approximately 5 tsp (25 mL) for research-related tests.

Tumor Biopsy: Immediately prior to cryoablation, a tissue sample from your tumor will be obtained. This sample will be collected for research. You may decline this biopsy. However, If you decline the biopsy, you will not be able to participate in this study.

Medication Review  
Physical Exam and Vital Signs and Weight Performance Status Patient Questionnaire Side Effect Review Blood Samples o Routine blood tests (chemistry and hematology tests) o Research blood tests o Pregnancy test (if you are female and able to become pregnant) o Other blood tests: ACTH, serum cortisol, TSH, fT4, CRP, and ESR.  
You will receive the study drugs in outpatient infusion room.
The total amount of blood to be collected at this Cycle 2 (Week 4) visit is approximately 8 teaspoons (tsp): Approximately 1.4 tsp (7 mL) for routine blood tests plus pregnancy test and approximately 1.5 tsp (7.5 mL) for Other blood tests and approximately 5 tsp (25 mL) for research-related tests.

Medication Review  
Physical Exam and Vital Signs and Weight Performance Status Patient Questionnaire Side Effect Review Blood Samples o Routine blood tests (chemistry and hematology tests) o Research blood tests o Pregnancy test (if you are female and able to become pregnant) o Other blood tests as appropriate  
  
You will receive the study drugs in outpatient infusion room.  
  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma The total amount of blood to be collected at this Cycle 3 (Week 7) visit is approximately 6.5 teaspoons (tsp): Approximately 1.4 tsp (7 mL) for routine blood tests plus pregnancy test and approximately 5 tsp (25 mL) for research-related tests.

Medication Review  
Physical Exam and Vital Signs and Weight Performance Status Patient Questionnaire Side Effect Review Blood Samples o Routine blood tests (chemistry and hematology tests) o Research blood tests o Pregnancy test (if you are female and able to become pregnant) o Other blood tests as appropriate Tumor Imaging/Measurements You will receive the study drugs in outpatient infusion room.
The total amount of blood to be collected at this Cycle 4 (Week 10) visit is approximately 6.5 teaspoons (tsp): Approximately 1.4 tsp (7 mL) for routine blood tests plus pregnancy test and approximately 5 tsp (25 mL) for research-related tests.

Medication Review  
Physical Exam and Vital Signs and Weight Performance Status Patient Questionnaire Side Effect Review  
  
  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma Blood Samples o Routine blood tests (chemistry and hematology tests)  
o Pregnancy test (if you are female and able to become pregnant) o Other blood tests as appropriate Tumor Imaging/Measurements You will receive the study drugs in outpatient infusion room.
The total amount of blood to be collected at Day 1 of Cycle 5 through 21 visits is approximately 6.5 teaspoons (tsp) per visit: Approximately 1.4 tsp (7 mL) for routine blood tests plus pregnancy test and approximately 5 tsp (25 mL) for research-related tests.

Medication Review  
Physical Exam and Vital Signs and Weight Performance Status Patient Questionnaire Side Effect Review Blood Samples o Routine blood tests (chemistry and hematology tests) o Research blood tests o Other blood tests as appropriate Optional Tumor Biopsy: After completion of study treatment, a post-treatment tissue sample of your tumor will be obtained if feasible.

Research using specimens is an important way to try to understand human disease. You have been given this information because the investigators want to include your specimens in a research project and because they want to save the specimens for future research. There are several things you should know before allowing your specimens to be studied. Your research specimens will be stored at Stanford University for up to 30 years. You will not be identified by name. Only your assigned patient number will be used. You have the right to refuse to allow your specimens to be studied now or saved for future study. You may withdraw from this study at any time. The investigators might retain the identified specimens, e.g., as part of your routine clinical care, but not for additional research. You will be told the results of tests that are part of your clinical care, but you will not be told the results of the research tests, including any future research tests.
Clinical trial: NCT04118166
Section: Purpose of Research
Subsections: Purpose Of Research|Why Is This Study Being Done?|What Is The Purpose Of This Research Study And How Will My Health Information Be Utilized In The Study?

You are invited to participate in a research study of ipilimumab plus nivolumab in combination with cryotherapy to treat metastatic or locally advanced soft tissue sarcoma. The use of these study drugs (ipilimumab and nivolumab) for soft tissue sarcoma is experimental. This means that they have not been approved by the United States Food and Drug Administration (FDA) for the treatment of soft tissue sarcoma.

We hope to find out:  
Will the study drugs in combination with cryotherapy help participants with metastatic or locally advanced soft tissue sarcoma?  
How safe are ipilimumab plus nivolumab given in combination with cryotherapy, and what side effects may be related to treatment?  
How do the study drugs in combination with cryotherapy work in soft tissue sarcoma? In order to better understand this, we will look at certain proteins in your blood and in your tumor.
You were selected as a possible participant in this study because metastatic or locally advanced soft tissue sarcoma. If you decide to terminate your participation in this study, you should notify Dr Kristen Ganjoo at 650-725-6413. This research study is looking for 30 participants with metastatic or locally advanced soft tissue sarcoma. Stanford University expects to enroll 30 research study participants.

The purpose of this research study is to evaluate the safety and efficacy of ipilimumab plus nivolumab in combination with cryotherapy to treat metastatic or locally advanced soft tissue sarcoma. The results will be provided to the study funder
(Bristol-Myers Squibb), the Food and Drug Administration and other federal and regulatory agencies as required.
Clinical trial: NCT04118166
Section: Voluntary Participation
Subsections: Voluntary Participation

Your participation in this study is entirely voluntary. Your decision not to participate will not have any negative effect on you or your medical care. You can decide to participate now, but withdraw your consent later and stop being in the study without any loss of benefits or medical care to which you are entitled.
Clinical trial: NCT04118166
Section: Withdrawal from Study
Subsections: Withdrawal From Study|If I Sign, Can I Revoke It Or Withdraw From The Research Later?

If you first agree to participate and then you change your mind, you are free to withdraw your consent and discontinue your participation at any time. Your decision will not affect your ability to receive medical care for your disease and you will not lose any benefits to which you would otherwise be entitled. If you decide to withdraw your consent to participate in this study, you should  
 notify Dr Kristen Ganjoo at (650) 725-6413.  
  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma If you withdraw from the study, or the study medication is stopped for any reason, (a) you must notify the study doctor, (b) you will be asked to return to the clinic for the end of treatment visit within 30 days of the last time you receive study drug. Your study doctor will talk to you about any medical problems that may happen if you stop taking part in the study. The Protocol Director may also withdraw you from the study and the study medication may be stopped without your consent for one or more of the following reasons:  
o Failure to follow the instructions of the Protocol Director and study staff.  
o The Protocol Director decides that continuing your participation could be harmful to you.  
o Pregnancy o You need treatment not allowed in the study. o The study is cancelled. o Other administrative reasons.  
o Unanticipated circumstances.

If you decide to participate, you are free to withdraw your authorization regarding the use and disclosure of your health information (and to discontinue any other participation in the study) at any time. After any revocation, your health information will no longer be used or disclosed in the study, except to the extent that  
  
  
Protocol Title: Phase II Study of Ipilimumab Plus Nivolumab in Combination with Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma the law allows us to continue using your information (e.g., necessary to maintain integrity of research). If you wish to revoke your authorization for the research use or disclosure of your health information in this study, you must write to: Dr Kristen Ganjoo, Stanford University Medical Center, 875 Blake Wilbur Drive, Stanford, CA 94305.