In-Situ Therapeutic Cancer Vaccine for Refractory Liver Cancer

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Biological: AlloStim


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>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 | Biological: AlloStim<br>* allogeneic Th1 memory cell with CD3/CD28-coated microbeads attached.<br>* Other names: InSituVax;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | Subjects will be followed by physical exam, blood labs, CT scan and biopsy for any adverse events | baseline to 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor-Specific Immunity | Determine if the in-situ vaccine elicits detectable tumor specific immunity | 90 days | 
| Anti-Tumor Response | Determine by radiological, pathological, immunological and by tumor markers any evidence of anti-tumor immune-mediated response. | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCC, liver cancer, tumor vaccine, immunotherapy