Clinical trial: NCT03508726
Section: Alternatives
Subsections: What Other Treatment Options Are There?

Before you decide whether or not to be in this study, your doctor will discuss the other options that are available to you. Instead of being in this study, you could receive the standard treatment for your disease or opt to be in a different clinical trial.
Clinical trial: NCT03508726
Section: Confidentiality
Subsections: What About Confidentiality?|Will My Health Information Be Used During This Study?

We will keep your participation in this research study confidential to the extent permitted by law. However, it is possible that other people such as those indicated below may become aware of your participation in this study and may inspect and copy records pertaining to this research. Some of these records could contain information that personally identifies you. - federal government regulatory agencies, - the U.S. Food and Drug Administration (FDA) - the Holden Comprehensive Cancer Center - auditing departments of the University of Iowa, and - the University of Iowa Institutional Review Board (a committee that reviews and approves research studies)
To help protect your confidentiality, we will keep study documents and binders in locked offices. Electronic information will be stored on password protected computers. Where feasible, we will use a research ID to minimize using your name. All printed documents are stored in a locked office at the hospital. Any blood samples that we take for research testing are dated and named using your Research ID. They are also stored at the University in a locked room. If we write a report or article about this study or share the study data set with others, we will do so in such a way that you cannot be directly identified. The University of Iowa Hospitals and Clinics generally requires that we document in your medical record chart that you are participating in this study. The information included in the chart will provide contact information for the research team as well as information about the risks associated with this study. We will keep this Informed Consent Document in our research files; it will not be placed in your medical record chart. A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This website will not include information that can identify you. At most, the website will include a summary of the results. You can search this website at any time.

The Federal Health Insurance Portability and Accountability Act (HIPAA) requires your healthcare provider to obtain your permission for the research team to access or create "protected health information" about you for purposes of this research study. Protected health information is information that personally identifies you and relates to your past, present, or future physical or mental health condition or care. We will access or create health information about you, as described in this document, for purposes of this research study and for your treatment. Once your healthcare provider has disclosed your protected health information to us, it may no longer be protected by the Federal HIPAA privacy regulations, but we will continue to protect your confidentiality as described under "Confidentiality." We may share your health information related to this study with other parties including federal government regulatory agencies, the University of Iowa Institutional Review Boards and support staff, the U.S. Food and Drug Administration, and the Data and Safety Monitoring Board of the Holden Comprehensive Cancer Center. You cannot participate in this study unless you permit us to use your protected health information. If you choose not to allow us to use your protected health information, we will discuss any non-research alternatives available to you. Your decision will not affect your right to medical care that is not research-related. Your signature on this Consent Document authorizes your healthcare provider to give us permission to use or create health information about you. Although you may not be allowed to see study information until after this study is over, you may be given access to your health care records by contacting your health care provider. Your permission for us to access or create protected health information about you for purposes of this study has no expiration date. You may withdraw your permission for us to use your health information for this research study by sending a written notice to:
Varun Monga, MBBS University of Iowa Hospitals & Clinics 200 Hawkins Drive, C21 GH Iowa City IA 52242 However, we may still use your health information that was collected before withdrawing your permission. Also, if we have sent your health information to a third party, such as the study sponsor, or we have removed your identifying information, it may not be possible to prevent its future use. You will receive a copy of this signed document.
Clinical trial: NCT03508726
Section: Duration of Study Involvement
Subsections: How Long Will I Be **In This Study?**

If you agree to take part in this study, your involvement will last for approximately 5 years. You will receive treatment with ascorbate three times a week for 5 weeks. You'll also receive radiation therapy during the same 5 weeks. Each visit will last from 2 - 4 hours. After your treatment has finished, you will have follow up visits according to recommended standard of care, for about 5 years.
Clinical trial: NCT03508726
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: What Are The Risks Of This Study?|Research Related **Risks**|Mild

You may experience one or more of the risks indicated below from being in this study. In addition to these, there may be other unknown risks, or risks that we did not anticipate, associated with being in this study.

Intravenous Ascorbate (Vitamin C) Serious - Diarrhea <10% - Nausea or vomiting <5% - Kidney stones <5% - Precipitation of cystine, oxalate or urate crystals in the kidney resulting in kidney damage or failure <1%

- Dry mouth/thirst (>35%) - Blood pressure elevation that may result in the need to be treated with medication <10% - Headache <5% - Abdominal pain <5% - Fatigue <5% - Facial flushing <5% - Sweating <5% - Weakness <5% - Injection site irritation may occur <2% - Faintness or dizziness may occur with rapid IV administration <5% - Ascorbic acid infusion may leak outside the vein, resulting in pain and irritation at the site <2%
Clinical trial: NCT03508726
Section: Procedures
Subsections: What Will Happen During This Study? Covid-19 Pandemic Adjustments|Before You Begin The Study Treatment|During Your Study Treatment|After Your Study Treatment

Due to the coronavirus pandemic (COVID-19), your doctors or study nurses may choose to skip some research-only tests. These tests are not for safety and do not impact your well-being. These are:  
- Ascorbate levels - Research blood sampling for biomarkers (how the ascorbate affects your body) - Research-MR imaging (T2*)
You can also decline to have these tests done if you would prefer to reduce your time at UIHC. Normally, you would have your MRIs and blood tests performed at UIHC for this study. However, due to the pandemic, your doctor may want to you to have these tests done elsewhere. If so, the tests results will be sent to UIHC and reviewed by your cancer doctors. They will also be added to your UIHC medical record.

You will need to have some tests done to find out if you can continue to be in the study. Some of these tests are part of regular cancer care and may be done even if you do not join the study treatment. If you have had some of them recently, they may not need to be repeated. This is up to your doctor.  
- Medical history  
- You will have blood drawn for research labs prior to the test dose of ascorbate to check the oxidative stress markers in your blood.  
- An optional MRI may be done if your tumor is in your extremities and if you agree. This is a research-only procedure done to see if a new type of MRI will be useful in planning for radiation therapy treatment. There will be a place at the end of this consent form to let us know if you agree to this MRI.  
- Physical examination including vital signs. - Electrocardiogram (ECG) to check the function of your heart. - Blood will be taken to determine blood counts, kidney function, liver function, electrolyte levels, and levels of an enzyme in your blood called G6PD. The result of the G6PD test will be added to your medical record.  
- Pregnancy test (if you are a woman of child-bearing potential). The results of this test will also be added to your medical record.  
- CT scan of the chest, abdomen and pelvis. The CT scans done during this study are considered standard of care.  
- MRI of your arms and/or legs if your tumor is located there.  
  
- A 15 gram test dose of ascorbate via IV infusion will be administered. If you do have a serious side effect or a significant medical event in the opinion of the study doctor, you will not continue in the study. Your study doctor will let you know if you are unable to continue in the study.  
- If you agree, we would like to take an optional tumor biopsy from you at this time, in order to compare the immune markers on your tumor from before treatment is started to samples we take after you receive treatment. To perform the biopsies, ultrasound will be used to guide a needle into the tumor which will be used to remove a core sample of the tumor. These biopsies will be used for only for research, they will not contribute to decisions about your care. You do not have to agree to this optional biopsy to participate in this study, Please initial your choice below:
_______ Yes, I agree to allow a biopsy of my tumor to be collected prior to receiving any study drug, to be used on this study as well stored for future research. _______ No, I do not want to participate in the pre treatment biopsy High dose ascorbate may interfere with finger-stick blood glucose readings. If you are using a finger-stick glucometer, you must discuss this with the study doctor. You may not be able to participate in this study.

If the tests show you can proceed, you will begin receiving treatment. - You will have blood drawn weekly during the 5 weeks of treatment to check your blood counts, kidney function, liver function and electrolyte levels. You will also have blood drawn for research labs during weeks 1, 3 and 5 as well as when you've finished treatment.  
- Physical examinations (including vital signs such as blood pressure and pulse) will be done during visits at weeks 1, 3 and 5.  
- You will receive ascorbate infusions three times a week for 5 weeks. You'll also receive radiation therapy daily, Monday - Friday, during the same 5 weeks.  
- At various points throughout the study visit you will be asked about changes in your health and/or use of medications.  
- Three optional MRIs may be done if your tumor is in your extremities and if you agree. These would be done at the following times:
o During screening as part of your planning in radiation oncology or as part of a diagnostic MRI
if that is being done (listed above in the list of tests done before you begin study treatment).  
o During week 3 of treatment.  
o At the end of the study.

- You will have a follow-up appointment in the Holden Comprehensive Cancer Center 4 to 6 weeks after your final ascorbate treatment.  
- Follow up appointments will be scheduled to see how you are doing, according to the standard of care, for about 5 years or until progression of your cancer is seen.
Clinical trial: NCT03508726
Section: Purpose of Research
Subsections: What Is The Purpose Of This Study?

This is a research study. We are inviting you to participate in this research study because you have sarcoma in one of your extremities, your trunk or in the retroperitoneum that can't be removed by surgery and you are a candidate for preoperative radiation therapy. The purpose of this research study is to see if high dose ascorbate (Vitamin C) in combination with radiation therapy will reduce the size of your tumor. We hope that high doses of ascorbate together with radiation therapy will work better in killing the cancer cells, than either treatment alone. High dose ascorbate is not approved by the U.S. Food and Drug Administration for any cancer. It is considered investigational for patients with locally advanced soft tissue sarcoma of the extremity, trunk and retroperitoneum, which means that it has not been approved by the U.S. Food and Drug Administration. The combination of high-dose ascorbate and radiation therapy has been shown to be safe and well tolerated in patients with glioblastoma multiforme, but has not been studied in patients with sarcoma.
Clinical trial: NCT03508726
Section: Voluntary Participation
Subsections: Is Being In This Study Voluntary?

Taking part in this research study is completely voluntary. You may choose not to take part at all. If you decide to be in this study, you may stop participating at any time. If you decide not to be in this study, or if you stop participating at any time, you won't be penalized or lose any benefits for which you otherwise qualify.
Clinical trial: NCT03508726
Section: Withdrawal from Study
Subsections: What If I Decide To Drop Out Of The Study?|Can Someone Else End My Participation In This Study?

If you decide to leave the study early, we will ask you to discuss your cancer treatment plans with your doctors so that you continue to receive clinical treatment for your cancer. We will also:  
  

IRB ID #: 201901810 APPROVAL DATE: 02/24/22 EXPIRATION DATE: 02/24/23
- need to take blood samples to make sure your kidneys, liver, and bone marrow are functioning - meet with you to discuss the side effects, if any, you had from ascorbate

Under certain circumstances, the researchers or study sponsor might decide to end your participation in this research study earlier than planned. This might happen because you have a bad reaction to the study drug or because in our judgment it would not be safe for you to continue. . Under certain circumstances, the University of Iowa or the Governor of Iowa may determine that all human subjects research must be halted due to COVID-19. If this happens, we will tell you as soon as we are notified. We will work with you and your doctors to ensure your standard cancer care continues.