In-Situ Therapeutic Cancer Vaccine for Refractory Liver Cancer
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.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Feasibility Study of ALLOSTIM(TM) in Combination With Radiofrequency Ablation in Patients With Refractory Hepatocellular Carcinoma|
- Safety [ Time Frame: baseline to 90 days ] [ Designated as safety issue: Yes ]Subjects will be followed by physical exam, blood labs, CT scan and biopsy for any adverse events
- Tumor-Specific Immunity [ Time Frame: 90 days ] [ Designated as safety issue: No ]Determine if the in-situ vaccine elicits detectable tumor specific immunity
- Anti-Tumor Response [ Time Frame: 90 days ] [ Designated as safety issue: No ]Determine by radiological, pathological, immunological and by tumor markers any evidence of anti-tumor immune-mediated response.
|Study Start Date:||November 2013|
|Estimated Study Completion Date:||June 2015|
|Estimated Primary Completion Date:||November 2014 (Final data collection date for primary outcome measure)|
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
allogeneic Th1 memory cell with CD3/CD28-coated microbeads attached.
Other Name: InSituVax
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01923233
|Hadassah-Hebrew University Medical Center|
|Study Director:||Yaron Ilan, MD||Hadassah Medical Organization|
|Principal Investigator:||Liat Applebaum, MD||Hadassah Medical Organization|
|Principal Investigator:||Saleh Daher, MD||Hadassah Medical Center|
|Principal Investigator:||Ariel Drori, MD||Hadassah Medical Center|