Condition category
Cancer
Date applied
10/10/2018
Date assigned
22/10/2018
Last edited
22/10/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Some viruses called oncolytic viruses can specifically target tumor cells, but not healthy cells and tissues. However, the patients’ immune system can eliminate most of the injected viral particles. This clinical study aims to overcome this issue by mixing the oncolytic viral particles with some of the patient's cells called stem cells. The stem cells would make the oncolytic viruses invisible to the patient's immune system during transport to the tumor sites. This study will evaluate the safety of the stem cells incubated with oncolytic virus in patients with advanced tumors. This study aims to recruit 30 patients with advanced tumors. The goal is to
evaluate the safety of this novel treatment approach in patients with advanced tumors. This study will also evaluate the anti-tumor effects of this treatment.

Who can participate?
Adults over the age of 18 who have advanced tumors

What does the study involve?
Participants are asked to join this study in their oncologist's clinic. Participants must pass the screening criteria for this study. Participants will be treated once and all treatment procedures will be completed within 3 hours. Patients will receive a combination of systemic intravenous and/or regional intratumoral deployment by a single injection. The study lasts one year in total. Participants are asked to give 7 small blood samples at the beginning, during and at the end of the study to test for the blood levels for virus DNA and specific proteins. Participants also complete online questionnaires every week during the study period.

What are the possible benefits and risks of participating?
There may or may not be immediate direct benefit to those taking part. There should be benefits to future treatment protocols for cancer therapies. The main risk of this treatment would be chills, low-grade fever and other flu-like symptoms in the first 8-24 hours. Therefore, doctors will continue to follow routine safety procedures to monitor participants for 24 hours following treatment.

Where is the study run from?
This study is being run by the Cell Surgical Network (USA) and takes place in two clinical centers located in Rancho Mirage, CA and Beverly Hills, CA (USA)

When is the study starting and how long is it expected to run for?
December 2015 to July 2017

Who is funding the study?
Cell Surgical Network (USA)

Who is the main contact?
1. Dr. Elliot Lander, MD (elliot@cellsurgicalnetwork.com)
2. Dr. Mark Berman, MD (mark@cellsurgicalnetwork.com)

Trial website

Contact information

Type

Scientific

Primary contact

Dr Boris Minev

ORCID ID

Contact details

10210 Campus Point Dr
Suite 150
SAN DIEGO
92121
United States of America

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

SI-01

Study information

Scientific title

The safety of autologous adipose derived SVF combined with the ACAM2000 (Vaccinia) vaccine in patients with advanced solid tumors

Acronym

Study hypothesis

Oncolytic viruses can target advanced solid malignancies with increased uptake and replication of the virus in cancer tissue. However, the patients’ immune system can neutralize most of the viral particles after deployment. We suggest that the oncolytic viral particles taken up by autologous stem cells would be invisible to the host immune system during transport to the tumor sites. Stem cells also exhibit a natural tropism towards cancer and can be exploited to carry the viral payloads directly to the cancer microenvironment, thus eluding the host immune system. This study evaluated safety of autologous Stromal Vascular Fraction (SVF) cells incubated with oncolytic vaccinia virus in patients with advanced solid tumors.

Ethics approval

Institutional Review Board (IRB) of the International Cell Surgical Society (ICSS), 28/08/2015, approval number ICSS-2015-007

Study design

Interventional open-label non-randomised study

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

GP practices

Trial type

Treatment

Patient information sheet

No participant information sheet available

Condition

Advanced solid tumors

Intervention

Patients were treated with autologous stromal vascular fraction (SVF) derived from autologous fat incubated for 15 minutes to 1 hour with oncolytic vaccinia virus ACAM2000. Patients received a combination of systemic intravenous and/or regional intratumoral deployment, which included intra-peritoneal or intra-nodal injections. The dose range for ACAM2000 in this trial was between 1.4x10⁶ pfu and 1.8x10⁷ pfu.
The total duration of the study was 3 years and 19 days.
Adverse events will be monitored throughout the study until resolution. In addition, all patients will respond to a weekly questionnaire answering specific questions on their current condition. Participants will be asked to give 7 small blood samples at the beginning, during and at the end of the study to test for the blood levels for virus DNA and specific proteins.

Intervention type

Biological/Vaccine

Phase

Drug names

Primary outcome measure

Safety of autologous adipose-derived stromal vascular fraction (SVF) combined with oncolytic vaccinia virus ACAM2000 in patients with advanced solid tumors, assessed using:
1. Patient interviews, weekly throughout the study period
2. Physical examinations at 1 day, 1 month, and 3, 6 and 12 months after treatment

Secondary outcome measures

1. Anti-tumor effects of the SVF/ACAM2000 administration, assessed at 3, 6 and 12 months after treatment using:
1.1. Physical examination
1.2. Imaging
2. Anti-vaccinia and anti-tumor immune responses following administration of SVF/ACAM2000, assessed at 1 day, 1 month, and 3, 6 and 12 months after treatment using:
2.1. Blood sample analysis for plasma cytokines
2.2. Flow cytometry

Overall trial start date

01/07/2015

Overall trial end date

19/07/2018

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Ability to understand and the willingness to sign a written informed consent
2. Histologically proven diagnosis of advanced (AJCC, 7th addition: stage III or IV) or aggressive (published disease-specific survival rates less than 20% at 5 years following best currently available therapies) solid organ cancer
3. Have no continuing acute toxic effects of any prior therapy, including but not limited to:
3.1. Biological therapy
3.2. Radiotherapy
3.3. Chemotherapy
3.4. Surgical procedures
All such effects must have resolved to Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0) Grade ≤1. Any other
surgery (except biopsies) must have occurred at least 28 days prior to study enrollment
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
5. Have a life expectancy of at least 3 months
6. Adequate organ and marrow function
7. Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control, or abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
8. Women of child-bearing potential has negative pregnancy test prior to initiating study drug dosing
9. Be willing and able to comply with scheduled visits, the treatment plan, imaging and laboratory tests

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

30

Participant exclusion criteria

1. Current or anticipated use of other investigational agents or marketed anticancer agent while on study
2. Received chemotherapy or radiotherapy within 4 weeks prior to entering the study or has not recovered from adverse events due to agents administered more than 4 weeks earlier
3. Patients who are less than 4 weeks from surgery (except biopsies) or have insufficient recovery from surgical-related trauma or wound healing
4. Have known immune system disorders (including acquired immunodeficiency syndrome (AIDS), HIV infection or hepatitis B or C). Eligible patients must have a negative HIV test result within 4 weeks prior to study initiation
5. Receiving additional immunosuppressive therapy or any steroids (except concurrent corticosteroid usage if no more than 20 mg per day, prednisolone equivalent is applied)
6. Received prior gene therapy or therapy with cytolytic virus of any type
7. Have clinically significant cardiac disease (New York Heart Association Class III or IV) including pre-existing arrhythmia, uncontrolled angina pectoris, and myocardial infarction one year prior to study entry, or Grade 2 or higher compromised left ventricular ejection fraction
8. Pulse oximetry oxygen saturation <90% at rest
9. Dementia or altered mental status that would prohibit informed consent
10. Severe or uncontrolled medical disorder that would, in the investigator’s opinion, impair ability to receive study treatment (i.e. ncontrolled diabetes, chronic renal disease, chronic pulmonary disease or active, fever, systemic and/or uncontrolled infections, psychiatric illness/social situations that would limit compliance with study requirements)
11. Be receiving concurrent antiviral agent active against vaccinia virus (e.g., cidofovir, vaccinia immunoglobulin, imatinib, ST-246) during the course of study
12. Have known allergy to ovalbumin or other egg products
13. Have clinically significant dermatological disorders (e.g., eczema, psoriasis, or any unhealed skin wounds or ulcers) as assessed by the Principal Investigator during screening and during the study
14. Have a history of allergy to iodinated contrast media
15. Have an active dental infection or recent dental work within 2 weeks of deployment
16. Known brain metastases
17. Pregnant or nursing
18. Condition does not seem to be one that can be improved with SVF/ACAM2000 as determined by one or more of our physician team

Recruitment start date

01/12/2015

Recruitment end date

19/07/2017

Locations

Countries of recruitment

United States of America

Trial participating centre

California Stem Cell Treatment Center
72-780 Country Club Drive Suite 301
Rancho Mirage, CA
92270
United States of America

Trial participating centre

Cell Surgical Network
120 S Spalding Dr., Suite 300
Beverly Hills, CA
90212
United States of America

Sponsor information

Organisation

Calidi Biotherapeutics

Sponsor details

10210 Campus Point Dr.
Suite 150
San Diego
92121
United States of America

Sponsor type

Industry

Website

Funders

Funder type

Not defined

Funder name

California Stem Cell Treatment Center

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Publication of clinical trial data in a medical journal.

IPD sharing statement:
The data sharing plans for the current study are unknown and will be made available at a later date

Intention to publish date

01/02/2019

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes