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General Questions:

What should one expect during a clinical trial/research study?

For all types of clinical research trials or studies, participants work with a research or clinical trial team, including doctors, nurses, social workers, and other health care professionals. Prior to the trial/study, the research team will check the health of the participant and review any special instructions for study participation. As the clinical trial begins and throughout its duration, the research team will administer treatment, and monitor the participant on a regular basis to determine safety, tolerability (side effects) and effectiveness of the treatment. Ongoing communication is an important part of any clinical research study and after the trial has been completed the research team will stay in touch with the participant for a specified period of time to assess any effects of the treatment after treatment has stopped. The data collected before, during and after the clinical trial is a crucial component to the drug’s approval submission to drug regulatory agencies.

What is informed consent?

Informed consent is the verification of a person’s willingness to participate in a research project. Prior to enrollment in a clinical trial, researchers inform participants about all relevant study details and known risks. Participants are then provided an informed consent document that details all the important study information including its purpose, duration, risks, potential benefits, required procedures, and key contacts. Once participants have had a chance to read this form and ask questions, if they agree to participate in the trial, they will be asked to sign an informed consent document.

What are my rights as a clinical trial participant?

You have the right to not take part in this, or any other clinical research study.

You have the right to drop out at any time.

You have the right to be given new information about the study.

You have the right to ask questions at any time and have them answered as soon as possible.

You also have the responsibility to stay informed during your participation in a study. You should ask questions about anything you do not understand or simply want to know.

Am I allowed to withdraw from the study because I feel the treatment course is not right for me, my condition has worsened, or for any other reason, including personal reasons?

Participation in a clinical trial is voluntary and the participant may withdraw from the study at any time without penalty or loss of benefits to which he/she is otherwise entitled. In many cases, the decision to discontinue with or withdraw from the study will be made based on consultation with, and based on data about the patients’ medical condition, and what his/her best course of action may be in light of this information. Sometimes, the decision to withdraw is a personal one, and has to do more with a patient’s not wishing/being able to submit to the terms of the protocol, including follow-on testing. Throughout the course of a patient’s participation in a clinical trial, we encourage the patient to communicate openly with his/or her medical research team, ask questions and discuss any worries or difficulties that may arise.

Will it cost me anything to take part in this clinical trial?

No. The experimental treatment as well as tests and procedures associated with this clinical study are provided at no cost to the participant. In most cases, the cost of routine tests and procedures—not associated with the clinical research study—are the responsibility of the participant, or the participant’s insurance carrier.

What happens after the course of treatment is completed?

Even after a patient has completed his/her treatment, ongoing communication is an important part of any clinical trial to evaluate any post-study short term or long-term benefit(s) and/or adverse effect(s). The data collected before, during and after the trial is a crucial component to the experimental treatment’s approval submission to drug regulatory agencies.

What is a clinical protocol?

The clinical trial protocol describes the rules to follow during this research study. For example, a protocol states why it is important to study stem cell/vaccinia anti-cancer therapy, the research question and how the research team will answer critical questions related to safety, tolerability and potential effect of this experimental treatment. The protocol also states specifically how the research team will protect the health and well-being of the trial participants. The protocol includes information on the study procedures, treatment and administration timelines and details, possible risks and benefits, possible adverse events and how they will be addressed, and data analysis methods.

How are patients protected when they participate in this clinical trial?

The protection of the rights and privacy of human subjects involved in research activities is mandated by federal law.  The National Research Act Public Law 99-158, The Health Research Extension Act of 1985, and the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research provide guidelines for research with human subjects to ensure their protection in the design and conduct of research.

The Institutional Review Board (IRB) at the International Cell Surgical Society protects people in this clinical trial. The IRB is registered (HHS-OMB Number – 0990-0279) with the Office for Human Research Protections (OHRP), which provides leadership in the protection of the rights, welfare, and well-being of human subjects involved in research conducted or supported by the U.S. Department of Health and Human Services (HHS).  The IRB includes a cross section of lay and professional members with different backgrounds including, clinicians, researchers, PhDs bioethicists, attorneys, and business experts. The IRB reviews, approves, and monitors all research in which people take part. This oversight keeps risks to research participants as low as possible. The IRB also keeps track of ongoing studies to make sure they are being done in the right way. The IRB requires that all researchers treat research participants with respect. The IRB protects your rights and welfare if you take part in a research study.

Who monitors the conduct of the protocol governing this clinical research study?

Physicians, nurses, sponsors, the Institutional Review Board (IRB)of the International Cell Surgical Society, and federal and non-federal regulatory bodies carefully monitor the actual conduct and safety of protocols. This means that different groups are reviewing the safety and progress of each protocol on a regular basis. If any of these groups determine that there is a concern with how the clinical trial is being conducted, the study will stop.

How do I contact the IRB?

If you have a concern, complaint or compliment about this clinical trial, please contact the International Cell Surgical Society IRB. The IRB takes all complaints very seriously. The IRB investigates all complaints and concerns. You may contact the IRB at any time by calling or emailing:

Austin Knudsen, Executive Director, ICSS

760-464-0181
www.internationalcellsurgicalsociety.org

Who is sponsoring this clinical trial?

This clinical trial is co-sponsored by:

Calidi Biotherapeutics Corporation

3655 Nobel Drive, Ste. 490
San Diego, CA 92122

T:858-794-9600
F:  (858) 794-9605

Cell Surgical Network

72780 Country Club Drive,
Building C, Suite 301
Rancho Mirage, CA 92270-4150

T: 800 231-0407
F: 760 776-0041

Questions Specific to Stem Cell/Vaccinia Combination Clinical Trial:

I understand this is a “safety study”. What is a safety study, and is this the same thing as a Phase I clinical trial?

Yes, this safety study is a Phase I clinical trial seeking primarily to establish the safety and tolerability of a new experimental stem cell/vaccinia combination anti-cancer therapy. Clinical trials evaluating new experimental drugs or treatments are conducted in a series of steps called Phases, and each Phase seeks to answer a specific research question. In a Phase I, or safety study, researchers test a new drug or treatment in a small group of people for the first time to evaluate safety, determine a safe dosage range and identify side effects. In an oncology clinical trial, there are often secondary outcomes designed to identify any early signs of efficacy (effectiveness or benefit) that may give valuable insights for structuring later stage trials involving larger numbers of patients, and seeking eventually to establish the effectiveness of an experimental drug or treatment.

What is background of the clinical trial involving stem cell/vaccinia combination anti-cancer therapy? What are the objectives of this clinical study?

Vaccinia- the most widely administered, successful medical product in history: Recent medical studies have shown that some patients with cancer may be helped by vaccinia virus when used as a cancer therapy alone, or in combination with other marketed therapies (like chemotherapy and radiation). Vaccinia virus is the most widely administered and successful medical product in history due to its use as a live vaccine against smallpox, which was declared eradicated by the World Health Organization (WHO) in 1980. The smallpox vaccine was used in millions of people with well-documented safety record. The most commonly seen adverse reactions to the vaccinia virus have been flu-like symptoms that are easily managed. The total number of serious reactions have occurred in < 14 incidences per million vaccinations. In addition, vaccinia immune globulin (VIG) is a “rescue medication” available to effectively treat a potential generalized vaccinia infection.

Vaccinia as an investigational anti-cancer therapy: In recent years, a growing body of preclinical evidence and human clinical trial data has shown the vaccinia virus to selectively enter and destroy cancer cells, without harming healthy tissues and cells – and all with little to no side effects. In human clinical trials, treatment with vaccinia virus has been proven well-tolerated, and even been associated with documented anti-tumor effects. Yet these studies have also shown that our immune systems eliminate much of the vaccinia virus as soon as it enters our bloodstream, making it less likely the virus will survive long enough to find its cancer targets. Medical scientists are working on ways to address this limitation and to help the anti-cancer vaccinia virus more successfully reach the cancer cells it is capable of killing.

To this end, there is evidence that our own stem cells may actually be able to carry, protect and deliver the vaccinia virus directly to tumors, where it can exert its cancer killing effect on tumor cells. Our own stem cells are uniquely qualified to shield the vaccinia virus from detection by our immune systems since they are not seen as “foreign”- they are rather seen by the immune system as part of ourselves, and so can effectively escape detection.

Objectives of this clinical study: This clinical trial is evaluating the safety, tolerability, feasibility and effects of combining these “stealth” carrying capabilities of a patient’s own stem cells, armed with a “payload” of the cancer killing vaccinia virus to target a variety of difficult to treat cancers.

Who is eligible for the clinical trial involving stem cell/vaccinia combination anti-cancer therapy?

This clinical trial involving stem cell/vaccinia combination therapy is offered to patients diagnosed with advanced cancer, who meet specific medical screening criteria established in the study protocol, and who have agreed to comply with all requirements of the research program.

The Principal Investigator (PI) will pre-screen prospective participants, reviewing their complete medical history and conditions. After the initial screening, a patient will see one of our oncologists overseeing patient selection for the study. The patient’s candidacy for participation will ultimately be reviewed by the study’s Tumor Board, consisting of medical oncologists, interventional radiologists and research scientists for review and recommendation.

In terms of specific criteria used to qualify patients, adherence to those established in the clinical trial’s protocol ensure that the treatment is being investigated accurately and safely. Factors that allow someone to participate in a clinical trial are called “inclusion criteria,” and those that disallow someone from participating are called “exclusion criteria.”  During the screening process, the PI, oncologist and the study’s Tumor Board together will ensure adherence to the

inclusion and exclusion criteria for this particular trial.

Important Note: Failure by a patient to completely disclose medical history and conditions, obtain recommended/ required testing and comply strictly with the protocol, could expose him/her to serious medical risks, including disability and death. 

In what types of cancer is this experimental stem cell/vaccinia anti-cancer therapy being tested?

The experimental treatment will be tested in patients with advanced (stage III or IV) solid organ cancer. The types of cancers being studied include, but are not limited to:

Metastatic melanoma;

Esophageal and gastric adenocarcinoma (Stage III/IV);

Cholangiocarcinoma (any stage);

Pancreatic adenocarcinoma (any stage);

Gallbladder cancer (any stage);

High-grade mucinous appendix cancer (any stage);

High-grade gastrointestinal neuroendocrine cancer (any stage);

Mesothelioma (any stage);

High-grade soft tissue sarcoma (any stage);

Prostate cancer

Renal cell carcinoma (Kidney)

Lung, small cell carcinoma

Lung, non-small cell carcinoma

Head and neck squamous cell carcinoma

Colorectal cancer

Ovarian carcinoma

Hepatocellular Carcinoma

Glioblastoma

Breast cancer

What are the potential benefits of participating in this clinical trial?

Overall benefits to participating in this medical research study may include: playing an active role in one’s health care, gaining access to treatments that may not be available for a significant amount of time, and helping others by participating in the trial so the treatment can potentially be approved and made available to the public.

This experimental stem cell/vaccinia anti-cancer therapy may result in an improvement in your cancer condition. Although patients may benefit from this experimental treatment, some patients will experience significant benefit, some will experience some benefit and some patients will not experience any benefit or improvement in their condition. Also, the degree of benefit may vary from patient to patient.

Because this is a new and experimental treatment, we do not know the long term effects of stem cell therapy, or whether/how long the immune response triggered by vaccinia therapy (virotherapy) may be effective against a cancer. We do not know, for example, if a stem cell/vaccinia administration will be effective 5-10 years after it is administered. To date, we know of no large study that has conclusively reviewed patients for cancer outcomes, or any long term side effect 5-10 years after a stem cell/vaccinia administration.

What specifically does the treatment involve in terms of office visits, additional tests, and follow-up?

Once a patient has signed his/her informed consent to participate in this clinical trial there are a series of steps, including office visits to administer and monitor treatment, as well as follow-on tests that will occur. While the Principal Investigators (PIs) will follow the treatment protocol, it may, in some cases, become medically necessary to adapt the treatment process to ensure a patient’s safety and comfort during the study. In general, the following elements and general timeframes are common to all patients participating in this clinical trial: (Click chart to open/save/print PDF.)

How or when will I know whether the treatment is having any effect on my cancer?

The primary objective of this clinical trial is to assess the safety and tolerability of an experimental stem cell/vaccinia combination anti-cancer therapy in patients with advanced cancers. A secondary objective is to determine whether there is early evidence of beneficial (therapeutic) effect in patients participating in this study.

Because this is an early stage safety study involving a completely new investigational therapy, it is difficult to predict whether a patient will benefit, or to what degree they may benefit. While later stage clinical trials will be designed more specifically and clearly to evaluate benefit/effect of this treatment, there will be a number of opportunities during the course of this safety study to gauge early evidence of efficacy (anti-cancer effect).

Each participating patient will be closely followed by the clinical trial’s medical research team to ensure safety and comfort during and after the stem cell/vaccinia treatment and throughout the monitoring period (12 months). During this extended time frame, the medical research team will perform a number of assessments that may give a window into various aspects of the treatment’s potential efficacy, including, but not limited to, a variety of blood tests, physical examinations, patient self-assessments, and at certain intervals, radiology evaluations (e.g. CT, PET, MRI, depending on the individual case) among other tests. It is important to remember that some patients may experience significant benefit from this experimental treatment, some will experience some benefit and some patients will not experience any benefit or improvement in their condition at all.

What should I do if I notice a rash, pox or “papules” on my skin after my treatment?

Sometimes, treatment with vaccinia virus will result in a rash. There are two types of skin rashes to consider in patients treated with vaccinia virus, and, while they are generally not problematic, it is nevertheless very important that you immediately call the Principal investigator (doctor who is administering this treatment) and have him/her evaluate any rash to determine whether it is vaccinia-specific or not.

Vaccinia-specific rashes: These rashes are usually characterized by the formation of a papule, vesicle, ulcer, or crusted lesion, surrounded by an area of induration (hardening of skin). They typically form as early as 2-5 days after treatment. Your doctor will likely culture the rash to determine whether it is vaccinia positive and whether there is a presence of fever.

If your rash is found to be vaccinia-positive, your doctor will review important precautionary measures to prevent spread to other parts of the body, or inadvertent transmission to another person. These instructions will apply to the study patient, family, friends, others, as well as to medical personnel.

Non-specific rashes: There are a few common non-specific rashes associated with vaccinia virus treatment or vaccination. These rashes do not contain vaccinia virus and are believed to be caused by an immune response to vaccinia virus application. These types of rashes usually are NOT accompanied by fever, can occur approximately 10 days after vaccinia virus application, resolve spontaneously within 2 to 4 days, and are usually self-limited. Your doctor may prescribe simple supportive care measures (e.g., oral anti-antihistamine agents).