Table 4.
Main on-going clinical trials of gene therapy for pancreatic cancer (source ClinicalTrials.gov, available online: https://clinicaltrials.gov/).
| Identification Number Date of Start Trial Stage | Phase, (Patient Number) | Route | Vector/Strategy |
|---|---|---|---|
| NCT00711997 August 2009 Completed | I/II (9) | IT CT- or US- or EUS-guided | jetPEI/DTA-H19 |
| NCT00669734 February 2010 Active, not recruiting | I (18) | IT or SC | Lowlpox and Vaccinia virus/PANVAC-V+ PANVAC-F + GM-CSF) |
| NCT01088789 April 2010 Recruiting | II (72) | ID | PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1 neo vaccine (allogenic pancreatic tumor cell vaccine transfected with the GM-CSF gene) +/− cyclophosphamide |
| NCT01191684 October 2011 Completed | I (2) | SC | Vaccinia virus/Vaccinia virus ankara vaccine expressing p53 |
| NCT01583686 April 2012 Recruiting | I/II (136) | IV | Rv/Anti-mesothelin CAR-T cell |
| NCT01836432 May 2013 Active, not recruiting | III (302) | ID | Rv/Algenpantucel-L +/− chemotherapy (Folfirinox or Gemcitabine + Nab-paclitaxel) |
| NCT02239861 September 2014 Recruiting | I (18) | IV | Tumor-associated antigen (TAA)-specific cytotoxic T lymphocytes 5 common TAAs: NY-ESO-1, MAGEA4, PRAME, Survivin and SSX. |
| NCT02340117 January 2015 Recruiting | II (28) | IV | Cationic liposome/SGT-53 + Gemcitabine + Nab-Paclitaxel |
| NCT02416466 April 2015 Active, not recruiting | I (8) | Percutan-eous hepatic artery infusion | SIR-Spheres microspheres/Anti-CEA CAR-T cells |
| NCT02465983 May 2015 Active, not recruiting | I (12) | IV | CART-meso-19 T cells + Cyclophosphamide |
| NCT02432963 November 2015 Recruiting | I (12) | ID | Vaccinia Ankara/Modified Vaccinia Ankara vector expressing full length wild type human p53 + Pembrolizumab |
| NCT02806687 June 2016 Recruiting | II (100) | IT EUS-guided | JetPEI/CYL-02 + Gemcitabine |
| NCT02576665 July 2016 Recruiting | I (26) | IV or IT | Rv/Toca 511 + Toca FC |
| NCT02894944 August 2016 Recruiting | I (9) | AdV/Theragene + Chemotherapy | |
| NCT02705196 November 2016 Not yet recruiting | I/II (26) | IT EUS- or US-guided | AdV/LOAd703 + Gemcitabine + Nab-paclitaxel |
IT: intratumoral route; ID: intradermal route; IV: intravenous route ; SC: subcutaneous route ; CT: CT scan; AdV: adenoviral vector; Rv: retroviral vector; CART-meso-19 T cells: patients′ own T cells modified to express a receptor specific to the mesothelin protein and receptor specific to CD19; DTA-H19: a doubled stranded DNA plasmid that carries the gene for the diphtheria toxin A (DT-A) chain under the regulation of the H19 promoter sequence; GVAX: allogenic pancreatic cancer cells expressing and secreting GM-CSF (plasmidic transfection); Algenpantucel-L: composed of two human pancreatic cancer cell lines genetically engineered to express αGal using a retroviral transfer. HSV-TK: herpes virus thymidine kinase that phosphorylate an antiherpetic prodrug valacyclovir becoming toxic for pancreatic cancer cells expressing the suicide gene HSV-TK; ADV-TK: Adenovirus-mediated herpes simplex virus thymidine kinase gene therapy; CYL-02: gene therapy product combining SSTR2 (human somatostatin receptor subtype 2), DCK (deoxycytine kinase) and UMK (uridyl moniphosphate kinase) genes and polycationic polyethylenimine vector with antioncogenic and chemosensitizing (gemcitabine) activities; LOAd703 : oncolytic adenovirus modified to include additional immune system stimulators; PANVAC-F: Intratumoral Recombinant Fowlpox PANVAC. PANVAC-V: Subcutaneous Recombinant Vaccinia PANVAC; SGT-53: complex of cationic liposome encapsulating a normal human wild type p53 DNA sequence in a plasmid backbone; Theragene: Replication-competent Adenovirus-mediated Double Suicide Gene Therapy (Theragene®, Ad5-yCD/mutTKSR39rep-ADP – Theragen Pharamceuticals Inc. San Diego, CA, USA); Toca 511: a retroviral replicating vector encoding a modified yeast cytosine deaminase (CD) gene; The CD gene converts the antifungal 5-flurocytosine (5FC) to the anticancer drug 5-FU in cells that have been infected by the Toca 511 vector; Toca FC: an extended-release formulation of flucytosine (Tocagen Company, San Diego, CA, USA).