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In-Situ Therapeutic Cancer Vaccine for Refractory Liver Cancer

Primary Purpose

Hepatocellular Carcinoma

Status

Withdrawn

Phase

Phase 1

Locations

Israel

Study Type

Interventional

Intervention

AlloStim

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring liver cancer, HCC, tumor vaccine, immunotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Any patients with a diagnosis of HCC based on histology or the current accepted radiological measures.
Age > 18 years.
Patient has an MRI or CT result (positive for HCC) up to 3 months prior to recruitment.
AFP >30.
Patient who is not eligible for or failed any HCC treatment.

Exclusion Criteria:

Patient is unable or unwilling to sign informed consent.
Patients that are participating in other clinical trials evaluating experimental treatments or procedures
Severe congestive heart failure (LVEF on echocardiogram < 20%).
Severe pulmonary hypertension (By echocardiogram, PAS >45 mmHg).
Uncontrolled diabetes mellitus (HBA1C >9.5%).
Any autoimmune disorder, which is currently being treated with prednisone or any other immune suppressive medication.
Patients currently receiving total parenteral nutrition if they have contraindications to oral drugs.
Subjects with positive HIV.
Women who are pregnant or breast feeding.
Patient, based on the opinion of the investigator, should not be enrolled into this study.
HBsAg positive or HBV DNA positive.
If the patient is HBcAB positive but HBsAG negative, irrespective of his anti HBS status, he can be enrolled but will receive preemptive therapy with Lamivudine.
Any metastasis except for portal vein involvement.
Subjects with Child Pugh above B8.
Prior experimental therapy or cancer vaccine treatment (e.g., dendritic cell therapy, heat shock vaccine).
History of blood transfusion reactions.
Known allergy to bovine or murine products

Sites / Locations

Hadassah-Hebrew University Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

Intradermal AlloStim(TM) (1ml) on day 0 and 3 in same location Intradermal AlloStim(TM) (1ml) on day 7 and day 10 in same location Radiofrequency ablation on day 14 followed by intralesional AlloStim (3ml) Intralesional AlloStim(TM)(3ml) on day 17 in same ablated lesion Intravenous AlloStim(TM)(5ml) on days 21, 49 and 78

Outcomes

Primary Outcome Measures

Safety

Subjects will be followed by physical exam, blood labs, CT scan and biopsy for any adverse events

Secondary Outcome Measures

Tumor-Specific Immunity

Determine if the in-situ vaccine elicits detectable tumor specific immunity

Anti-Tumor Response

Determine by radiological, pathological, immunological and by tumor markers any evidence of anti-tumor immune-mediated response.

Full Information

NCT ID

NCT01923233

First Posted

August 12, 2013

Last Updated

January 17, 2020

Sponsor

Immunovative Therapies, Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT01923233

Brief Title

In-Situ Therapeutic Cancer Vaccine for Refractory Liver Cancer

Official Title

Phase I Feasibility Study of ALLOSTIM(TM) in Combination With Radiofrequency Ablation in Patients With Refractory Hepatocellular Carcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

December 2015

Overall Recruitment Status

Withdrawn

Why Stopped

interventional radiologist suffered stroke and unable to perform RFA procedure

Study Start Date

November 2014 (Actual)

Primary Completion Date

June 2015 (Anticipated)

Study Completion Date

June 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Immunovative Therapies, Ltd.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This study is an individualized anti-cancer vaccine protocol where the vaccination occurs inside of the body. To create the vaccine, a tumor lesion is selected and caused to die by a process called "Radiofrequency Ablation" or RFA. RFA causes the tumor to release its internal contents to the surrounding environment, such contents include tumor-specific antigens. Immune cells respond to the tissue damage and take-up these tumor antigens. The injection of the experimental cell drug, AlloStim(TM) into the lesion is designed to cause the responding cells to signal the immune system of the danger of the tumor, creating tumor-specific immunity.

Detailed Description

The protocol design has 4 steps: (1) priming; (2) vaccination, (3) activation and (4) boosting. The priming step involves intradermal injections of AlloStim(TM). This is designed to increase the circulating titer of allo-specific Th1 memory cells; the vaccination step involves percutaneous radiofrequency ablation of a single liver lesion followed immediately with an intratumoral injection of AlloStim(TM) into the ablated lesion, followed 3 days later by an additional intratumoral injection into the previously ablated lesion with AlloStim(TM). This step is designed to elicit tumor-specific Th1 immunity. The activation step involves intravenous infusions of AlloStim(TM). This step is designed to cause the activation and extravasation of circulating memory cells and the activation of innate immune cells. The booster step includes two monthly IV infusions of AlloStim(TM). This step is designed to maintain an inflammatory cytokine storm designed to counteract immune suppressor mechanisms and tumor immunoavoidance mechanisms.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatocellular Carcinoma

Keywords

liver cancer, HCC, tumor vaccine, immunotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

AlloStim

Other Intervention Name(s)

InSituVax

Intervention Description

allogeneic Th1 memory cell with CD3/CD28-coated microbeads attached.

Primary Outcome Measure Information:

Title

Safety

Description

Subjects will be followed by physical exam, blood labs, CT scan and biopsy for any adverse events

Time Frame

baseline to 90 days

Secondary Outcome Measure Information:

Title

Tumor-Specific Immunity

Description

Determine if the in-situ vaccine elicits detectable tumor specific immunity

Time Frame

90 days

Title

Anti-Tumor Response

Description

Determine by radiological, pathological, immunological and by tumor markers any evidence of anti-tumor immune-mediated response.

Time Frame

90 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Any patients with a diagnosis of HCC based on histology or the current accepted radiological measures. Age > 18 years. Patient has an MRI or CT result (positive for HCC) up to 3 months prior to recruitment. AFP >30. Patient who is not eligible for or failed any HCC treatment. Exclusion Criteria: Patient is unable or unwilling to sign informed consent. Patients that are participating in other clinical trials evaluating experimental treatments or procedures Severe congestive heart failure (LVEF on echocardiogram < 20%). Severe pulmonary hypertension (By echocardiogram, PAS >45 mmHg). Uncontrolled diabetes mellitus (HBA1C >9.5%). Any autoimmune disorder, which is currently being treated with prednisone or any other immune suppressive medication. Patients currently receiving total parenteral nutrition if they have contraindications to oral drugs. Subjects with positive HIV. Women who are pregnant or breast feeding. Patient, based on the opinion of the investigator, should not be enrolled into this study. HBsAg positive or HBV DNA positive. If the patient is HBcAB positive but HBsAG negative, irrespective of his anti HBS status, he can be enrolled but will receive preemptive therapy with Lamivudine. Any metastasis except for portal vein involvement. Subjects with Child Pugh above B8. Prior experimental therapy or cancer vaccine treatment (e.g., dendritic cell therapy, heat shock vaccine). History of blood transfusion reactions. Known allergy to bovine or murine products

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael Har-Noy

Organizational Affiliation

Immunovative Therapies, Ltd.

Official's Role

Study Director

Facility Information:

Facility Name

Hadassah-Hebrew University Medical Center

City

Jerusalem

Country

Israel

12. IPD Sharing Statement

Citations:

PubMed Identifier

23786302

Citation

Epple LM, Bemis LT, Cavanaugh RP, Skope A, Mayer-Sonnenfeld T, Frank C, Olver CS, Lencioni AM, Dusto NL, Tal A, Har-Noy M, Lillehei KO, Katsanis E, Graner MW. Prolonged remission of advanced bronchoalveolar adenocarcinoma in a dog treated with autologous, tumour-derived chaperone-rich cell lysate (CRCL) vaccine. Int J Hyperthermia. 2013 Aug;29(5):390-8. doi: 10.3109/02656736.2013.800997. Epub 2013 Jun 20.

Results Reference

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PubMed Identifier

23734882

Citation

Mayer-Sonnenfeld T, Har-Noy M, Lillehei KO, Graner MW. Proteomic analyses of different human tumour-derived chaperone-rich cell lysate (CRCL) anti-cancer vaccines reveal antigen content and strong similarities amongst the vaccines along with a basis for CRCL's unique structure: CRCL vaccine proteome leads to unique structure. Int J Hyperthermia. 2013 Sep;29(6):520-7. doi: 10.3109/02656736.2013.796529. Epub 2013 Jun 4.

Results Reference

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PubMed Identifier

22075702

Citation

LaCasse CJ, Janikashvili N, Larmonier CB, Alizadeh D, Hanke N, Kartchner J, Situ E, Centuori S, Har-Noy M, Bonnotte B, Katsanis E, Larmonier N. Th-1 lymphocytes induce dendritic cell tumor killing activity by an IFN-gamma-dependent mechanism. J Immunol. 2011 Dec 15;187(12):6310-7. doi: 10.4049/jimmunol.1101812. Epub 2011 Nov 9.

Results Reference

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PubMed Identifier

21123824

Citation

Janikashvili N, LaCasse CJ, Larmonier C, Trad M, Herrell A, Bustamante S, Bonnotte B, Har-Noy M, Larmonier N, Katsanis E. Allogeneic effector/memory Th-1 cells impair FoxP3+ regulatory T lymphocytes and synergize with chaperone-rich cell lysate vaccine to treat leukemia. Blood. 2011 Feb 3;117(5):1555-64. doi: 10.1182/blood-2010-06-288621. Epub 2010 Dec 1.

Results Reference

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PubMed Identifier

18834631

Citation

Har-Noy M, Zeira M, Weiss L, Fingerut E, Or R, Slavin S. Allogeneic CD3/CD28 cross-linked Th1 memory cells provide potent adjuvant effects for active immunotherapy of leukemia/lymphoma. Leuk Res. 2009 Apr;33(4):525-38. doi: 10.1016/j.leukres.2008.08.017. Epub 2008 Oct 1.

Results Reference

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PubMed Identifier

18054441

Citation

Har-Noy M, Slavin S. The anti-tumor effect of allogeneic bone marrow/stem cell transplant without graft vs. host disease toxicity and without a matched donor requirement? Med Hypotheses. 2008;70(6):1186-92. doi: 10.1016/j.mehy.2007.10.008. Epub 2007 Dec 3.

Results Reference

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In-Situ Therapeutic Cancer Vaccine for Refractory Liver Cancer

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